Sample records for delivery vehicle rheology

  1. A magneto rheological hybrid damper for railway vehicles suspensions

    Directory of Open Access Journals (Sweden)

    Gheorghe GHITA


    Full Text Available High speed railway vehicles features a specific lateral oscillation resulting from the coupled lateral displacement and yaw of the wheelset which leads to a sinusoid movement of the wheelset along the track, transferred to the entire vehicle. The amplitude of this oscillation is strongly dependant on vehicle’s velocity. Over a certain value, namely the critical speed, the instability phenomenon so-called hunting occurs. To raise the vehicle’s critical speed different designs of the suspension all leading to a much stiffer vehicle can be envisaged. Different simulations prove that a stiffer central suspension will decrease the passenger’s comfort in terms of lateral accelerations of the carboy. The authors propose a semi-active magneto rheological suspension to improve the vehicle’s comfort at high speeds. The suspension has as executive elements hybrid magneto rheological dampers operating under sequential control strategy type balance logic. Using an original mathematical model for the lateral dynamics of the vehicle the responses of the system with passive and semi-active suspensions are simulated. It is shown that the semi-active suspension can improve the vehicle performances.

  2. 30 CFR 56.6802 - Bulk delivery vehicles. (United States)


    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Bulk delivery vehicles. 56.6802 Section 56.6802... § 56.6802 Bulk delivery vehicles. No welding or cutting shall be performed on a bulk delivery vehicle until the vehicle has been washed down and all explosive material has been removed. Before welding...

  3. 30 CFR 57.6802 - Bulk delivery vehicles. (United States)


    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Bulk delivery vehicles. 57.6802 Section 57.6802...-Surface and Underground § 57.6802 Bulk delivery vehicles. No welding or cutting shall be performed on a bulk delivery vehicle until the vehicle has been washed down and all explosive material has...

  4. Transdermal Delivery of Nisoldipine: Refinement of Vehicles. (United States)

    El Maghraby, Gamal M; Ahmed, Amal A; Osman, Mohamed A


    Nisoldipine is used for the treatment of hypertension and angina pectoris. However, it has very low bioavailabil-ty, which is attributed to extensive pre-systemic metabolism. In addition, nisol-ipine is highly potent (used at a low dose). Taking into consideration the fact that transdermal delivery avoids the pre-systemic metabolism and is only suit-ble for potent drugs, nisoldipine can be considered as an excellent candidate for transdermal delivery. Accordingly, the purpose of this study was to optimize nisoldipine transdermal delivery. That was achieved initially by investigating the effect of vehicles on skin penetration. The tested vehicles were ranked with respect to transdermal flux of nisoldipine as isopropyl myristate > oleic acid > propylene glycol > water > polyethylene glycol 400. A combination of oleic acid with propylene glycol was synergistic with a ratio of 1:2 w/w being the best. These results were taken further to develop microemulsion systems using either oleic acid or isopropyl myristate as the oil phase. Both cases employed polyoxy-thylene sorbitan monooleate as a surfactant with propylene glycol being uti-ized as a cosurfactant in the case of oleic acid and ethanol in the case of isopropyl myristate. The developed microemulsions produced significant enhancement in nisoldipine transdermal delivery with the flux being even greater than that obtained from the corresponding pure vehicles. This achieve-ent was recorded in optimum microemulsion formulations which contained a cosurfactant. The study provided stepwise optimization of a vehicle for trans-ermal delivery of nisoldipine.

  5. Molecular imprinted polymers as drug delivery vehicles. (United States)

    Zaidi, Shabi Abbas


    This review is aimed to discuss the molecular imprinted polymer (MIP)-based drug delivery systems (DDS). Molecular imprinted polymers have proved to possess the potential and also as a suitable material in several areas over a long period of time. However, only recently it has been employed for pharmaceuticals and biomedical applications, particularly as drug delivery vehicles due to properties including selective recognition generated from imprinting the desired analyte, favorable in harsh experimental conditions, and feedback-controlled recognitive drug release. Hence, this review will discuss their synthesis, the reason they are selected as drug delivery vehicles and for their applications in several drug administration routes (i.e. transdermal, ocular and gastrointestinal or stimuli-reactive routes).

  6. Vibration control of a semi-active railway vehicle suspension with magneto-rheological dampers

    Directory of Open Access Journals (Sweden)

    Jong-Seok Oh


    Full Text Available This article presents vibration control performances of a semi-active railway vehicle suspension system using a magneto-rheological damper tested on the roller rig. In order to evaluate control performances, a mathematical railway vehicle model with 15 degrees of freedom is first derived to represent the lateral, yaw and roll motions of the car body, bogie frame, and wheel set, respectively. Based on the formulated model, the design parameters of magneto-rheological damper are determined to undertake a compatible comparison with dynamic performances of conventional (existing passive railway vehicle suspension system. The designed magneto-rheological damper is manufactured and its field-dependent damping force characteristics are experimentally evaluated. Subsequently, in order to enhance the ride quality of a railway vehicle suspension equipped with magneto-rheological damper, a skyhook controller associated with an extended Kalman filter is designed in a state space representation. The railway suspension system incorporated with the car body and two bogies is then experimentally set up on the roller rig in order to evaluate the ride quality. It is demonstrated from experimental realization of the controller that the ride quality of the suspension system with magneto-rheological damper can be significantly enhanced compared with the existing passive suspension system.

  7. Engineering Delivery Vehicles for Genome Editing. (United States)

    Nelson, Christopher E; Gersbach, Charles A


    The field of genome engineering has created new possibilities for gene therapy, including improved animal models of disease, engineered cell therapies, and in vivo gene repair. The most significant challenge for the clinical translation of genome engineering is the development of safe and effective delivery vehicles. A large body of work has applied genome engineering to genetic modification in vitro, and clinical trials have begun using cells modified by genome editing. Now, promising preclinical work is beginning to apply these tools in vivo. This article summarizes the development of genome engineering platforms, including meganucleases, zinc finger nucleases, TALENs, and CRISPR/Cas9, and their flexibility for precise genetic modifications. The prospects for the development of safe and effective viral and nonviral delivery vehicles for genome editing are reviewed, and promising advances in particular therapeutic applications are discussed.

  8. Rheological behavior and stability of ciprofloxacin suspension: Impact of structural vehicles and flocculating agent

    Directory of Open Access Journals (Sweden)

    Eskandar Moghimipour


    Full Text Available Ciprofloxacin is a fluoroquinolone and is used against a broad spectrum of gram-negative and gram-positive bacteria. The aim of the study is to investigate the effect of structural vehicles and other formulating factors on physical stability and rheological behavior of ciprofloxacin suspension. To formulate the suspensions, the effect of glycerin and polysorbate 80 as wetting agents was evaluated. Then to achieve controlled flocculation, different concentrations of sodium chloride and calcium chloride were added. After choosing suitable wetting and flocculating agents, structural vehicles such as sodium carboxyl methyl cellulose (NaCMC, hydroxypropylmethylcellulose (HPMC and Veegum were evaluated. Physical stability parameters such as sedimentation volume, the degree of flocculation and the ease of redispersion of the suspensions and growth of crystals were evaluated. After incorporation of structural vehicles, the rheological properties of formulations containing were also studied to find out their rheological behavior. According to the results, suspension containing glycerin (0.2% w/v and sodium chloride (0.05% w/v as wetting agent and flocculating agent, respectively, were the most stable formulations regarding their F and N. Microscopic observations showed the growth of crystals in ciprofloxacin suspension in formulation without excipients and the minimum amount of crystal growth was seen in suspension containing NaCMC (0.25% w/v, Veegum (0.1% w/v and NaCl (0.05% w/v. Rheological studies showed that almost all of the formulations had psuedoplastic behavior with different degree of thixotropy. The formulation containing NaCMC (0.25% w/v, Veegum (0.1% w/v and NaCl (0.05% w/v was the most stable formulation. It may be concluded that by altering the amount ratios of formulation factors, the best rheological behavior and the most proper thixotropy may be achieved.

  9. Semi-active sliding mode control of vehicle suspension with magneto-rheological damper (United States)

    Zhang, Hailong; Wang, Enrong; Zhang, Ning; Min, Fuhong; Subash, Rakheja; Su, Chunyi


    The vehicle semi-active suspension with magneto-rheological damper(MRD) has been a hot topic since this decade, in which the robust control synthesis considering load variation is a challenging task. In this paper, a new semi-active controller based upon the inverse model and sliding mode control (SMC) strategies is proposed for the quarter-vehicle suspension with the magneto-rheological (MR) damper, wherein an ideal skyhook suspension is employed as the control reference model and the vehicle sprung mass is considered as an uncertain parameter. According to the asymptotical stability of SMC, the dynamic errors between the plant and reference systems are used to derive the control damping force acquired by the MR quarter-vehicle suspension system. The proposed modified Bouc-wen hysteretic force-velocity ( F- v) model and its inverse model of MR damper, as well as the proposed continuous modulation (CM) filtering algorithm without phase shift are employed to convert the control damping force into the direct drive current of the MR damper. Moreover, the proposed semi-active sliding mode controller (SSMC)-based MR quarter-vehicle suspension is systematically evaluated through comparing the time and frequency domain responses of the sprung and unsprung mass displacement accelerations, suspension travel and the tire dynamic force with those of the passive quarter-vehicle suspension, under three kinds of varied amplitude harmonic, rounded pulse and real-road measured random excitations. The evaluation results illustrate that the proposed SSMC can greatly suppress the vehicle suspension vibration due to uncertainty of the load, and thus improve the ride comfort and handling safety. The study establishes a solid theoretical foundation as the universal control scheme for the adaptive semi-active control of the MR full-vehicle suspension decoupled into four MR quarter-vehicle sub-suspension systems.

  10. Semi-active Sliding Mode Control of Vehicle Suspension with Magneto-rheological Damper

    Institute of Scientific and Technical Information of China (English)

    ZHANG Hailong; WANG Enrong; ZHANG Ning; MIN Fuhong; SUBASH Rakheja; SU Chunyi


    The vehicle semi-active suspension with magneto-rheological damper(MRD) has been a hot topic since this decade, in which the robust control synthesis considering load variation is a challenging task. In this paper, a new semi-active controller based upon the inverse model and sliding mode control (SMC) strategies is proposed for the quarter-vehicle suspension with the magneto-rheological (MR) damper, wherein an ideal skyhook suspension is employed as the control reference model and the vehicle sprung mass is considered as an uncertain parameter. According to the asymptotical stability of SMC, the dynamic errors between the plant and reference systems are used to derive the control damping force acquired by the MR quarter-vehicle suspension system. The proposed modified Bouc-wen hysteretic force-velocity (F-v) model and its inverse model of MR damper, as well as the proposed continuous modulation (CM) filtering algorithm without phase shift are employed to convert the control damping force into the direct drive current of the MR damper. Moreover, the proposed semi-active sliding mode controller (SSMC)-based MR quarter-vehicle suspension is systematically evaluated through comparing the time and frequency domain responses of the sprung and unsprung mass displacement accelerations, suspension travel and the tire dynamic force with those of the passive quarter-vehicle suspension, under three kinds of varied amplitude harmonic, rounded pulse and real-road measured random excitations. The evaluation results illustrate that the proposed SSMC can greatly suppress the vehicle suspension vibration due to uncertainty of the load, and thus improve the ride comfort and handling safety. The study establishes a solid theoretical foundation as the universal control scheme for the adaptive semi-active control of the MR full-vehicle suspension decoupled into four MR quarter-vehicle sub-suspension systems.

  11. Polymeric vehicles for topical delivery and related analytical methods. (United States)

    Cho, Heui Kyoung; Cho, Jin Hun; Jeong, Seong Hoon; Cho, Dong Chul; Yeum, Jeong Hyun; Cheong, In Woo


    Recently a variety of polymeric vehicles, such as micelles, nanoparticles, and polymersomes, have been explored and some of them are clinically used to deliver therapeutic drugs through skin. In topical delivery, the polymeric vehicles as drug carrier should guarantee non-toxicity, long-term stability, and permeation efficacy for drugs, etc. For the development of the successful topical delivery system, it is of importance to develop the polymeric vehicles of well-defined intrinsic properties, such as molecular weights, HLB, chemical composition, topology, specific ligand conjugation and to investigate the effects of the properties on drug permeation behavior. In addition, the role of polymeric vehicles must be elucidated in in vitro and in vivo analyses. This article describes some important features of polymeric vehicles and corresponding analytical methods in topical delivery even though the application span of polymers has been truly broad in the pharmaceutical fields.

  12. Thermoresponsive fluconazole gels for topical delivery: rheological and mechanical properties, in vitro drug release and anti-fungal efficacy. (United States)

    Gandra, Sarath C R; Nguyen, Sanko; Nazzal, Sami; Alayoubi, Alaadin; Jung, Rose; Nesamony, Jerry


    The aim of this study was to develop thermosensitive gels using poloxamers for topical delivery of fluconazole (FLZ). Eight different formulations containing 1% FLZ in poloxamer and a particular co-solvent (propylene glycol (PG) or Transcutol-P) of various concentrations were prepared. The gels were characterized for transition temperatures, rheological and mechanical properties. FLZ permeability and antifungal effect of the gels were also evaluated. Except for one formulation, all gels exhibited thermosensitive property, i.e. transformed from Newtonian (liquid-like) behavior at 20 °C to non-Newtonian (gel-like) behavior at 37 °C. Transcutol-P increased the transition temperature of the formulations, while the opposite effect was observed for PG. At 37 °C, formulations with high poloxamer concentrations (17%) resulted in high viscosity, compressibility and hardness. Formulations containing 17% poloxamer and 20% Transcutol-P and 10% PG, respectively, exhibited high adhesiveness. No significant differences in the in vitro antifungal activity of FLZ were observed among the formulations suggesting that the gel vehicles did not influence the biological effect of FLZ. FLZ permeability decreased with increasing poloxamer concentration. Formulations containing 17% poloxamer and 20% Transcutol-P and 10% PG seemed to be promising in situ gelling systems for the topical delivery of FLZ.

  13. Amphotericin B cochleates: a vehicle for oral delivery. (United States)

    Perlin, David S


    Cochleates are a novel lipid-based delivery vehicle consisting of crystalline phospholipid-cation structures that form spiral lipid sheets. They represent a new technology platform for oral delivery of clinically important drugs that possess poor oral bioavailability. Orally administered cochleates containing amphotericin B (CAMB) showed broad-spectrum activity in murine infection models of candidiasis, aspergillosis and cryptococcosis. Initial biodistribution studies of CAMB administered orally in mice demonstrated that cochleates delivered significant levels of AMB to target organs. The lipid particulate nature of cochleates also imparted reduced toxicity that mimics other lipid-amphotericin B complexes. Cochleates are a promising new vehicle for oral delivery of amphotericin B at therapeutic levels.

  14. Protease-triggered siRNA delivery vehicles. (United States)

    Rozema, David B; Blokhin, Andrei V; Wakefield, Darren H; Benson, Jonathan D; Carlson, Jeffrey C; Klein, Jason J; Almeida, Lauren J; Nicholas, Anthony L; Hamilton, Holly L; Chu, Qili; Hegge, Julia O; Wong, So C; Trubetskoy, Vladimir S; Hagen, Collin M; Kitas, Eric; Wolff, Jon A; Lewis, David L


    The safe and efficacious delivery of membrane impermeable therapeutics requires cytoplasmic access without the toxicity of nonspecific cytoplasmic membrane lysis. We have developed a mechanism for control of cytoplasmic release which utilizes endogenous proteases as a trigger and results in functional delivery of small interfering RNA (siRNA). The delivery approach is based on reversible inhibition of membrane disruptive polymers with protease-sensitive substrates. Proteolytic hydrolysis upon endocytosis restores the membrane destabilizing activity of the polymers thereby allowing cytoplasmic access of the co-delivered siRNA. Protease-sensitive polymer masking reagents derived from polyethylene glycol (PEG), which inhibit membrane interactions, and N-acetylgalactosamine, which targets asialoglycoprotein receptors on hepatocytes, were synthesized and used to formulate masked polymer-siRNA delivery vehicles. The size, charge and stability of the vehicles enable functional delivery of siRNA after subcutaneous administration and, with modification of the targeting ligand, have the potential for extrahepatic targeting.

  15. Rheological Behavior of Xanthan Gum Solution Related to Shear Thinning Fluid Delivery for Subsurface Remediation

    Energy Technology Data Exchange (ETDEWEB)

    Zhong, Lirong; Oostrom, Martinus; Truex, Michael J.; Vermeul, Vincent R.; Szecsody, James E.


    Xanthan gum, a biopolymer, forms shear thinning fluids which can be used as delivery media to improve the distribution of remedial amendments injected into heterogeneous subsurface environments. The rheological behavior of the shear thinning solution needs to be known to develop an appropriate design for field injection. In this study, the rheological properties of xanthan gum solutions were obtained under various chemical and environmental conditions relevant to delivery of remedial amendments to groundwater. Higher xanthan concentration raised the absolute solution viscosity and increased the degree of shear thinning. Addition of remedial amendments (e.g., phosphate, sodium lactate, ethyl lactate) caused the dynamic viscosity of xanthan gum to decrease, but the solutions maintained shear-thinning properties. Use of simple salt (e.g. Na+, Ca2+) to increase the solution ionic strength also decreased the dynamic viscosity of xanthan and the degree of shear thinning, although the effect is a function of xanthan gum concentration and diminished as the xanthan gum concentration was increased. At high xanthan concentration, addition of salt to the solution increased dynamic viscosity. In the absence of sediments, xanthan gum solutions maintain their viscosity properties for months. However, xanthan gum solutions were shown to lose dynamic viscosity over a period of days to weeks when contacted with saturated site sediment. Loss of viscosity is attributed to physical and biodegradation processes.

  16. Oral delivery strategies for nutraceuticals: Delivery vehicles and absorption enhancers


    Gleeson, John P.; Ryan, Sinéad M.; Braden, David James


    Lifestyle issues contribute to the development of obesity, type 2 diabetes, and cardiovascular disease. Together with appropriate diet and exercise, nutraceuticals may contribute to managing prevention at an early stage prior to therapeutic intervention. However, many useful food-derived bioactive compounds will not sufficiently permeate the small intestine to yield efficacy without appropriate oral delivery technology. The pharmaceutical industry uses commercialised approaches for oral deliv...

  17. Nanostructured lipid carriers: versatile oral delivery vehicle. (United States)

    Poonia, Neelam; Kharb, Rajeev; Lather, Viney; Pandita, Deepti


    Oral delivery is the most accepted and economical route for drug administration and leads to substantial reduction in dosing frequency. However, this route still remains a challenge for the pharmaceutical industry due to poorly soluble and permeable drugs leading to poor oral bioavailability. Incorporating bioactives into nanostructured lipid carriers (NLCs) has helped in boosting their therapeutic functionality and prolonged release from these carrier systems thus providing improved pharmacokinetic parameters. The present review provides an overview of noteworthy studies reporting impending benefits of NLCs in oral delivery and highlights recent advancements for developing engineered NLCs either by conjugating polymers over their surface or modifying their charge to overcome the mucosal barrier of GI tract for active transport across intestinal membrane.

  18. Concentration-dependent rheological properties of ECM hydrogel for intracerebral delivery to a stroke cavity. (United States)

    Massensini, Andre R; Ghuman, Harmanvir; Saldin, Lindsey T; Medberry, Christopher J; Keane, Timothy J; Nicholls, Francesca J; Velankar, Sachin S; Badylak, Stephen F; Modo, Michel


    Biomaterials composed of mammalian extracellular matrix (ECM) promote constructive tissue remodeling with minimal scar tissue formation in many anatomical sites. However, the optimal shape and form of ECM scaffold for each clinical application can vary markedly. ECM hydrogels have been shown to promote chemotaxis and differentiation of neuronal stem cells, but minimally invasive delivery of such scaffold materials to the central nervous system (CNS) would require an injectable form. These ECM materials can be manufactured to exist in fluid phase at room temperature, while forming hydrogels at body temperature in a concentration-dependent fashion. Implantation into the lesion cavity after a stroke could hence provide a means to support endogenous repair mechanisms. Herein, we characterize the rheological properties of an ECM hydrogel composed of urinary bladder matrix (UBM) that influence its delivery and in vivo interaction with host tissue. There was a notable concentration-dependence in viscosity, stiffness, and elasticity; all characteristics important for minimally invasive intracerebral delivery. An efficient MRI-guided injection with drainage of fluid from the cavity is described to assess in situ hydrogel formation and ECM retention at different concentrations (0, 1, 2, 3, 4, and 8mg/mL). Only ECM concentrations >3mg/mL gelled within the stroke cavity. Lower concentrations were not retained within the cavity, but extensive permeation of the liquid phase ECM into the peri-infarct area was evident. The concentration of ECM hydrogel is hence an important factor affecting gelation, host-biomaterial interface, as well intra-lesion distribution. Extracellular matrix (ECM) hydrogel promotes constructive tissue remodeling in many tissues. Minimally invasive delivery of such scaffold materials to the central nervous system (CNS) would require an injectable form that exists in fluid phase at room temperature, while forming hydrogels at body temperature in a

  19. Delivery of Unmanned Aerial Vehicle Data (United States)

    Ivancic, William D.; Sullivan, Donald V.


    To support much of NASA's Upper Atmosphere Research Program science, NASA has acquired two Global Hawk Unmanned Aerial Vehicles (UAVs). Two major missions are currently planned using the Global Hawk: the Global Hawk Pacific (GloPac) and the Genesis and Rapid Intensification Processes (GRIP) missions. This paper briefly describes GloPac and GRIP, the concept of operations and the resulting requirements and communication architectures. Also discussed are requirements for future missions that may use satellite systems and networks owned and operated by third parties.

  20. The Role of Simulation Games: Supplement or Central Delivery Vehicle? (United States)

    Fritzsche, David J.


    Reports the results of an experiment assessing the effectiveness of two different approaches to using simulation games in a marketing course. In one, the game was used as a supplement to the standard lecture/discussion format; in the other, it was used as the central delivery vehicle. Twenty-one references are listed. (Author/LLS)

  1. Phage Particles as Vaccine Delivery Vehicles: Concepts, Applications and Prospects. (United States)

    Jafari, Narjes; Abediankenari, Saeid


    The development of new strategies for vaccine delivery for generating protective and long-lasting immune responses has become an expanding field of research. In the last years, it has been recognized that bacteriophages have several potential applications in the biotechnology and medical fields because of their intrinsic advantages, such as ease of manipulation and large-scale production. Over the past two decades, bacteriophages have gained special attention as vehicles for protein/peptide or DNA vaccine delivery. In fact, whole phage particles are used as vaccine delivery vehicles to achieve the aim of enhanced immunization. In this strategy, the carried vaccine is protected from environmental damage by phage particles. In this review, phage-based vaccine categories and their development are presented in detail, with discussion of the potential of phage-based vaccines for protection against microbial diseases and cancer treatment. Also reviewed are some recent advances in the field of phage- based vaccines.

  2. Novel adjuvants & delivery vehicles for vaccines development: a road ahead. (United States)

    Mohan, Teena; Verma, Priyanka; Rao, D Nageswara


    The pure recombinant and synthetic antigens used in modern day vaccines are generally less immunogenic than older style live/attenuated and killed whole organism vaccines. One can improve the quality of vaccine production by incorporating immunomodulators or adjuvants with modified delivery vehicles viz. liposomes, immune stimulating complexes (ISCOMs), micro/nanospheres apart from alum, being used as gold standard. Adjuvants are used to augment the effect of a vaccine by stimulating the immune system to respond to the vaccine, more vigorously, and thus providing increased immunity to a particular disease. Adjuvants accomplish this task by mimicking specific sets of evolutionary conserved molecules which include lipopolysaccharides (LPS), components of bacterial cell wall, endocytosed nucleic acids such as dsRNA, ssDNA and unmethylated CpG dinucleotide containing DNA. This review provides information on various vaccine adjuvants and delivery vehicles being developed to date. From literature, it seems that the humoral immune responses have been observed for most adjuvants and delivery platforms while viral-vector, ISCOMs and Montanides have shown cytotoxic T-cell response in the clinical trials. MF59 and MPL® have elicited Th1 responses, and virus-like particles (VLPs), non-degradable nanoparticle and liposomes have also generated cellular immunity. Such vaccine components have also been evaluated for alternative routes of administration with clinical success reported for intranasal delivery of viral-vectors and proteosomes and oral delivery of VLP vaccines.

  3. 41 CFR 101-26.501-6 - Forms used in connection with delivery of vehicles. (United States)


    ... with delivery of vehicles. 101-26.501-6 Section 101-26.501-6 Public Contracts and Property Management... connection with delivery of vehicles. (a) GSA Form 1398, GSA Purchased Vehicle. This form is used by the contractor to indicate that preshipment inspection and servicing of each vehicle has been performed....

  4. Design attributes of long-circulating polymeric drug delivery vehicles. (United States)

    Beck-Broichsitter, Moritz; Nicolas, Julien; Couvreur, Patrick


    Following systemic administration polymeric drug delivery vehicles allow for a controlled and targeted release of the encapsulated medication at the desired site of action. For an elevated and organ specific accumulation of their cargo, nanocarriers need to avoid opsonization, activation of the complement system and uptake by macrophages of the mononuclear phagocyte system. In this respect, camouflaged vehicles revealed a delayed elimination from systemic circulation and an improved target organ deposition. For instance, a steric shielding of the carrier surface by poly(ethylene glycol) substantially decreased interactions with the biological environment. However, recent studies disclosed possible deficits of this approach, where most notably, poly(ethylene glycol)-modified drug delivery vehicles caused significant immune responses. At present, identification of novel potential carrier coating strategies facilitating negligible immune reactions is an emerging field of interest in drug delivery research. Moreover, physical carrier properties including geometry and elasticity seem to be very promising design attributes to surpass numerous biological barriers, in order to improve the efficacy of the delivered medication.

  5. Macrophages as drug delivery vehicles for photochemical internalization (Conference Presentation) (United States)

    Madsen, Steen J.; Gonzalez, Jonathan; Molina, Stephanie; Kumar Nair, Rohit; Hirschberg, Henry


    Targeted delivery of chemotherapeutic drugs to tumor sites is a major challenge in cancer chemotherapy. Cell-based vectorization of therapeutic agents has great potential for cancer therapy in that it can target and maintain an elevated concentration of therapeutic agents at the tumor site and prevent their spread into healthy tissue. The use of circulating cells such as monocytes/macrophages (Ma) offers several advantages compared to nanoparticles as targeted drug delivery vehicles. Ma can be easily obtained from the patient, loaded in vitro with drugs and reinjected into the blood stream. Ma can selectively cross the partially compromised blood-brain barrier surrounding brain tumors and are known to actively migrate to tumors, drawn by chemotactic factors, including hypoxic regions where conventional chemo and radiation therapy are least effective. The utility of Ma as targeted drug delivery vehicles for photochemical internalization (PCI) of tumors was investigated in this study. In vitro studies were conducted using a mixture of F98 rat glioma cells and rat macrophages loaded with a variety of chemotherapeutic agents including bleomycin and 5-fluorouracil. Preliminary data show that macrophages are resistant to both chemotherapeutics while significant toxicity is observed for F98 cells exposed to both drugs. Co-incubation of F98 cells with loaded Ma results in significant F98 toxicity suggesting that Ma are releasing the drugs and, hence providing the rationale for their use as delivery vectors for cancer therapies such as PCI.

  6. Rheological behavior and Ibuprofen delivery applications of pH responsive composite alginate hydrogels. (United States)

    Jabeen, Suraya; Maswal, Masrat; Chat, Oyais Ahmad; Rather, Ghulam Mohammad; Dar, Aijaz Ahmad


    Synthesis and structural characterization of hydrogels composed of sodium alginate, polyethylene oxide and acrylic acid with cyclodextrin as the hydrocolloid prepared at different pH values is presented. The hydrogels synthesized show significant variations in rheological properties, drug encapsulation capability and release kinetics. The hydrogels prepared at lower pH (pH 1) are more elastic, have high tensile strength and remain almost unaffected by varying temperature or frequency. Further, their Ibuprofen encapsulation capacity is low and releases it slowly. The hydrogel prepared at neutral pH (pH 7) is viscoelastic, thermo-reversible and also exhibits sol-gel transition on applying frequency and changing temperature. It shows highest Ibuprofen encapsulation capacity and also optimum drug release kinetics. The hydrogel prepared at higher pH (pH 12) is more viscous, has low tensile strength, is unstable to change in temperature and has fast drug release rate. The study highlights the pH responsiveness of three composite alginate hydrogels prepared under different conditions to be employed in drug delivery applications.

  7. 45 CFR 1310.14 - Inspection of new vehicles at the time of delivery. (United States)


    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false Inspection of new vehicles at the time of delivery... Inspection of new vehicles at the time of delivery. Each agency providing transportation services must ensure that bid announcements for school buses and allowable alternate vehicles for use in...

  8. Polymer-based vehicles for therapeutic peptide delivery. (United States)

    Zhang, Jinjin; Desale, Swapnil S; Bronich, Tatiana K


    During the last decades increasing attention has been paid to peptides as potential therapeutics. However, clinical applications of peptide drugs suffer from susceptibility to degradation, rather short circulation half-life, limited ability to cross physiological barriers and potential immunogenicity. These challenges can be addressed by using polymeric materials as peptide delivery systems, owing to their versatile structures and properties. A number of polymer-based vehicles have been developed to stabilize the peptides and to control their release rates. Unfortunately, no single polymer or formulation strategy has been considered ideal for all types of peptide drugs. In this review, currently used and potential polymer-based systems for the peptide delivery will be discussed.

  9. Glucose-sensitive gel rheology of dextran-concanavalin A mixtures suitable for self-regulating insulin delivery. (United States)

    Taylor, M Joan; Tanna, Sangeeta; Sahota, Tarsem S


    Aqueous concentrated plain mixtures of dextran and concanavalin A (con A) were examined for their rheological response to glucose for comparison with previously studied partially photopolymerized acrylic derivatives. Non-destructive oscillatory tests were undertaken within the linear viscoelastic range to examine the relationship between the rheometry and the stoichiometry of the interactive materials and to examine rheological parameters as affected by molecular weight, component ratio, temperature and glucose concentrations between 0 and 1% w/w. These simple formulations were studied at 1 and 10 Hz at 0.5% strain at both 20 and 37 degrees C. A second simplified rheological test was undertaken to demonstrate gel-sol reversibility and to produce a measure of equilibria created between these gels and glucose solutions with which they are in contact. This mimics the conditions in which the gel acts as a responsive gateway in the insulin delivery device. It proved that the gels equilibrate with glucose solutions, rather than indiscriminately removing glucose. This is important in terms of producing a delivery device that can respond in a reversible, glucose concentration-dependent manner. The method used for this is capable of relative values only but provides information not obtainable from conventional rheometry.

  10. Exosomes as drug delivery vehicles for Parkinson's disease therapy. (United States)

    Haney, Matthew J; Klyachko, Natalia L; Zhao, Yuling; Gupta, Richa; Plotnikova, Evgeniya G; He, Zhijian; Patel, Tejash; Piroyan, Aleksandr; Sokolsky, Marina; Kabanov, Alexander V; Batrakova, Elena V


    Exosomes are naturally occurring nanosized vesicles that have attracted considerable attention as drug delivery vehicles in the past few years. Exosomes are comprised of natural lipid bilayers with the abundance of adhesive proteins that readily interact with cellular membranes. We posit that exosomes secreted by monocytes and macrophages can provide an unprecedented opportunity to avoid entrapment in mononuclear phagocytes (as a part of the host immune system), and at the same time enhance delivery of incorporated drugs to target cells ultimately increasing drug therapeutic efficacy. In light of this, we developed a new exosomal-based delivery system for a potent antioxidant, catalase, to treat Parkinson's disease (PD). Catalase was loaded into exosomes ex vivo using different methods: the incubation at room temperature, permeabilization with saponin, freeze-thaw cycles, sonication, or extrusion. The size of the obtained catalase-loaded exosomes (exoCAT) was in the range of 100-200nm. A reformation of exosomes upon sonication and extrusion, or permeabilization with saponin resulted in high loading efficiency, sustained release, and catalase preservation against proteases degradation. Exosomes were readily taken up by neuronal cells in vitro. A considerable amount of exosomes was detected in PD mouse brain following intranasal administration. ExoCAT provided significant neuroprotective effects in in vitro and in vivo models of PD. Overall, exosome-based catalase formulations have a potential to be a versatile strategy to treat inflammatory and neurodegenerative disorders.

  11. Casein/pectin nanocomplexes as potential oral delivery vehicles. (United States)

    Luo, Yangchao; Pan, Kang; Zhong, Qixin


    Delivery systems prepared with natural biopolymers are of particular interests for applications in food, pharmaceutics and biomedicine. In this study, nanocomplex particles of sodium caseinate (NaCas) and pectin were fabricated and investigated as potential oral delivery vehicles. Nanocomplexes were prepared with three mass ratios of NaCas/pectin by acidification using glucono-δ-lactone and thermal treatment. NaCas/pectin at 1:1 mass ratio resulted in dispersions with the lowest turbidity and the smallest and most uniform nanocomplexes. Thermal treatment at 85 °C for 30 min facilitated the formation of stable, compact, and spherical nanocomplexes. Heating not only greatly increased the yield of nanocomplexes but also significantly improved the encapsulation capability of rutin studied as a model compound. Pectin in nanocomplexes delayed the hydrolysis of NaCas by pepsin at gastric conditions and enabled the controlled release of most rutin in simulated intestinal conditions. The nanocomplexes based on food-sourced biopolymers have promising features for oral delivery of nutrients and medicines.

  12. Lipoamino acid-based micelles as promising delivery vehicles for monomeric amphotericin B. (United States)

    Serafim, Cláudia; Ferreira, Inês; Rijo, Patrícia; Pinheiro, Lídia; Faustino, Célia; Calado, António; Garcia-Rio, Luis


    Lipoamino acid-based micelles have been developed as delivery vehicles for the hydrophobic drug amphotericin B (AmB). The micellar solubilisation of AmB by a gemini lipoamino acid (LAA) derived from cysteine and its equimolar mixtures with the bile salts sodium cholate (NaC) and sodium deoxycholate (NaDC), as well as the aggregation sate of the drug in the micellar systems, was studied under biomimetic conditions (phosphate buffered-saline, pH 7.4) using UV-vis spectroscopy. Pure surfactant systems and equimolar mixtures were characterized by tensiometry and important parameters were determined, such as critical micelle concentration (CMC), surface tension at the CMC (γCMC), maximum surface excess concentration (Γmax), and minimum area occupied per molecule at the water/air interface (Amin). Rheological behaviour from viscosity measurements at different shear rates was also addressed. Solubilisation capacity was quantified in terms of molar solubilisation ratio (χ), micelle-water partition coefficient (KM) and Gibbs energy of solubilisation (ΔGs°). Formulations of AmB in micellar media were compared in terms of drug loading, encapsulation efficiency, aggregation state of AmB and in vitro antifungal activity against Candida albicans. The LAA-containing micellar systems solubilise AmB in its monomeric and less toxic form and exhibit in vitro antifungal activity comparable to that of the commercial formulation Fungizone.

  13. Polyamine-DNA interactions and development of gene delivery vehicles. (United States)

    Thomas, T J; Tajmir-Riahi, H A; Thomas, Thresia


    Polyamines are positively charged organic cations under physiologic ionic and pH conditions and hence they interact with negatively charged macromolecules such as DNA and RNA. Although electrostatic interaction is the predominant mode of polyamine-nucleic acid interactions, site- and structure-specific binding has also been recognized. A major consequence of polyamine-DNA interaction is the collapse of DNA to nanoparticles of approximately 100 nm diameter. Electron and atomic force microscopic studies have shown that these nanoparticles are spheroids, toroids and rods. DNA transport to cells for gene therapy applications requires the condensation of DNA to nanoparticles and hence the study of polyamines and related compounds with nucleic acids has received technological importance. In addition to natural and synthetic polyamines, several amine-terminated or polyamine-substituted agents are under intense investigation for non-viral gene delivery vehicles.

  14. Magnetotactic Bacterial Cages as Safe and Smart Gene Delivery Vehicles

    KAUST Repository

    Alsaiari, Shahad K.


    In spite of the huge advances in the area of synthetic carriers, their efficiency still poorly compares to natural vectors. Herein, we report the use of unmodified magnetotactic bacteria as a guidable delivery vehicle for DNA functionalized gold nanoparticles (AuNPs). High cargo loading is established under anaerobic conditions (bacteria is alive) through endocytosis where AuNPs are employed as transmembrane proteins mimics (facilitate endocytosis) as well as imaging agents to verify and quantify loading and release. The naturally bio-mineralized magnetosomes, within the bacteria, induce heat generation inside bacteria through magnetic hyperthermia. Most importantly after exposing the system to air (bacteria is dead) the cell wall stays intact providing an efficient bacterial vessel. Upon incubation with THP-1 cells, the magnetotactic bacterial cages (MBCs) adhere to the cell wall and are directly engulfed through the phagocytic activity of these cells. Applying magnetic hyperthermia leads to the dissociation of the bacterial microcarrier and eventual release of cargo.

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

    Ifju, Peter


    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).

  16. 41 CFR 101-26.4902-1781 - GSA Form 1781, Motor Vehicle Requisition-Delivery Order. (United States)


    ... 41 Public Contracts and Property Management 2 2010-07-01 2010-07-01 true GSA Form 1781, Motor Vehicle Requisition-Delivery Order. 101-26.4902-1781 Section 101-26.4902-1781 Public Contracts and... GSA Form 1781, Motor Vehicle Requisition—Delivery Order. Note: The form illustrated in §...

  17. Thermally reversible xyloglucan gels as vehicles for nasal drug delivery. (United States)

    Mahajan, Hitendra S; Tyagi, Vinod; Lohiya, Gopal; Nerkar, Pankaj


    The aim of this study was to investigate the potential application of thermosensitive gels formed by a xyloglucan polysaccharide derived from tamarind seed for nasal drug delivery. Xyloglucan that had been partially degraded by β-galactosidase to eliminate 45% of galactose residues formed gels at concentrations of 2.5% w/w at gelation temperatures decreasing over the range 27-28°C. The in vitro release of ondansetron hydrochloride from the enzyme-degraded xyloglucan gels followed higuchi kinetics over a period of 5 h at 34°C by anomalous transport mechanism. The ex vivo permeation of ondansetron hydrochloride from the gels was sustained. Histological examination of nasal mucosa following a single administration of the gels showed no evidence of mucosal damage. Finally, the bioavailability study in rabbits revealed that the absolute bioavailability of ondansetron hydrochloride was significantly increased from 28.64% in the case of the oral drug solution to 52.79% in the case of the nasal in situ gel. The results of this study suggest the potential of the enzyme-degraded xyloglucan gels as vehicles for nasal delivery of drugs.

  18. DNA nanotubes as intracellular delivery vehicles in vivo. (United States)

    Sellner, Sabine; Kocabey, Samet; Nekolla, Katharina; Krombach, Fritz; Liedl, Tim; Rehberg, Markus


    DNA-based nanoconstructs possess great potential for biomedical applications. However, the in vivo behavior of such constructs at the microscopic tissue/cell level as well as their inflammatory potential is largely unknown. Unmethylated CpG sequences of DNA are recognized by Toll-like receptor 9 (TLR9), and thus initiate an innate immune response. In this study, we investigated the use of DNA-based nanotubes as carrier systems for CpG delivery and their effect on immune cells in vivo and in real time. DNA nanotubes were microinjected into skeletal muscle of anesthetized mice. Using in vivo microscopy, we observed that the DNA tubes were internalized within minutes by tissue-resident macrophages and localized in their endosomes. Only microinjection of CpG-decorated DNA nanotubes but not of plain DNA nanotubes or CpG oligonucleotides induced a significant recruitment of leukocytes into the muscle tissue as well as activation of the NF-ĸB pathway in surrounding cells. These results suggest that DNA nanotubes are promising delivery vehicles to target tissue macrophages, whereupon the immunogenic potential depends on the decoration with CpG oligonucleotides.

  19. Polymeric microbubbles as delivery vehicles for sensitizers in sonodynamic therapy. (United States)

    McEwan, Conor; Fowley, Colin; Nomikou, Nikolitsa; McCaughan, Bridgeen; McHale, Anthony P; Callan, John F


    Microbubbles (MBs) have recently emerged as promising delivery vehicles for sensitizer drugs in sonodynamic therapy (SDT). The ability to selectively destroy the MB and activate the sensitizer using an external ultrasound trigger could provide a minimally invasive and highly targeted therapy. While lipid MBs have been approved for use as contrast agents in diagnostic ultrasound, the attachment of sensitizer drugs to their surface results in a significant reduction in particle stability. In this Article, we prepare both lipid and polymer (PLGA) MBs with rose bengal attached to their surface and demonstrate that PLGA MB conjugates are significantly more stable than their lipid counterparts. In addition, the improved stability offered by the PLGA shell does not hinder their selective destruction using therapeutically acceptable ultrasound intensities. Furthermore, we demonstrate that treatment of ectopic human tumors (BxPC-3) in mice with the PLGA MB-rose bengal conjugate and ultrasound reduced tumor volume by 34% 4 days after treatment while tumors treated with the conjugate alone increased in volume by 48% over the same time period. Therefore, PLGA MBs may offer a more stable alternative to lipid MBs for the site specific delivery of sensitizers in SDT.

  20. Silica nanoparticles as vehicles for therapy delivery in neurological injury (United States)

    Schenk, Desiree

    Acrolein, a very reactive aldehyde, is a culprit in the biochemical cascade after primary, mechanical spinal cord injury (SCI), which leads to the destruction of tissue initially unharmed, referred to as "secondary injury". Additionally, in models of multiple sclerosis (MS) and some clinical research, acrolein levels are significantly increased. This aldehyde overwhelms the natural anti-oxidant system, reacts freely with proteins, and releases during lipid peroxidation (LPO), effectively regenerating its self. Due to its ability to make more copies of itself in the presence of tissue via lipid peroxidation, researchers believe that acrolein plays a role in the increased destruction of the central nervous system in both SCI and MS. Hydralazine, an FDA-approved hypertension drug, has been shown to scavenge acrolein, but its side effects and short half life at the appropriate dose for acrolein scavenging must be improved for beneficial clinical translation. Due to the inefficient delivery of therapeutic drugs, nanoparticles have become a major field of exploration for medical applications. Based on their material properties, they can help treat disease by delivering drugs to specific tissues, enhancing detection methods, or a mixture of both. Nanoparticles made from silica provide distinct advantages. They form porous networks that can carry therapeutic molecules throughout the body. Therefore, a nanomedical approach has been designed using silica nanoparticles as a porous delivery vehicle hydralazine. The silica nanoparticles are formed in a one-step method that incorporates poly(ethylene) glycol (PEG), a stealth molecule, directly onto the nanoparticles. As an additional avenue for study, a natural product in green tea, epigallocatechin gallate (EGCG), has been explored for its ability to react with acrolein, disabling its reactive capabilities. Upon demonstration of attenuating acrolein, EGCG's delivery may also be improved using the nanomedical approach. The

  1. Liposomal nanoparticles as a drug delivery vehicle against osteosarcoma (United States)

    Dhule, Santosh Subhashrao

    The delivery of curcumin, a broad-spectrum anticancer drug, has been explored in the form of liposomal nanoparticles to treat osteosarcoma (OS). Curcumin is water insoluble and an effective delivery route is through encapsulation in cyclodextrins followed by a second encapsulation in liposomes. Liposomal curcumin's potential was evaluated against cancer models of mesenchymal (OS) and epithelial origin (breast cancer). The resulting 2-Hydroxypropyl-gamma-cyclodextrin/curcumin - liposome complex shows promising anticancer potential both in vitro and in vivo against KHOS OS cell line and MCF-7 breast cancer cell line. An interesting aspect is that liposomal curcumin initiates the caspase cascade that leads to apoptotic cell death in vitro in comparison with DMSO-curcumin induced autophagic cell death. In addition, the efficiency of the liposomal curcumin formulation was confirmed in vivo using a xenograft OS model. Curcumin-loaded gamma-cyclodextrin liposomes indicate significant potential as delivery vehicles for the treatment of cancers of different tissue origin. The second part of this study examines the anti-tumor potential of curcumin and C6 ceramide (C6) against osteosarcoma cell lines when both are encapsulated in the bilayer of liposomal nanoparticles. Curcumin in combination with C6 showed 1.5 times enhanced cytotoxic effect in the case of MG-63 and KHOS OS cell lines, in comparison with systems with curcumin alone. Interestingly, C6-curcumin liposomes were found to be less toxic on untransformed human cells in comparison to OS cell lines. In addition, cell cycle assays on a KHOS cell line after treatment revealed that curcumin only liposomes induced G 2/M arrest by upregulation of cyclin B1, while C6 only liposomes induced G1 arrest by downregulation of cyclin D1. C6-curcumin liposomes induced G2/M arrest and showed a combined effect in the expression levels of cyclin D1 and cyclin B1. Using pegylated liposomes to increase the plasma half-life and tagging

  2. AAV vectors as gene delivery vehicles in the central nervous system

    NARCIS (Netherlands)

    Broekman, M.L.D.


    Recombinant gene delivery vehicles based on the replication-defective AAV have gained a preeminent position in the field of gene delivery to the brain. Efficient global gene delivery to the CNS is beneficial for the study of gene products is the entire CNS as well as for introducing and expressing g


    Institute of Scientific and Technical Information of China (English)

    WANG Enrong; YING Liang; WANG Wanjun; RAKHEJA Subhash; SU Chunyi


    A modified skyhook-based semi-active controller is proposed for implementing an asymmetric control suspension design with symmetric magneto-rheological (MR) dampers. The controller is formulated in current form, which is modulated by integrating a continuous modulation and an asymmetric damping force generation algorithms, so as to effectively minimize switching and hysteretic effects from the MR-damper. The proposed controller is implemented with a quarter-vehicle MR-suspension model, and its relative response characteristics are thus evaluated in terms of defined performance measures under varying amplitude harmonic, rounded pulse and random excitations. The sensitivity of the semi-active suspension performance to variations in controller parameters is thoroughly evaluated. The results illustrate that the proposed skyhook-based asymmetric semi-active MR-suspension controller has superior robustness on the system parameter variations, and can achieve desirable multi-objective suspension performance.



    José Ferreira de Souza Neto; Vitória Pureza


    ABSTRACT This work addresses a vehicle routing problem that aims at representing delivery operations of large volumes of products in dense urban areas. Inspired by a case study in a drinks producer and distributor, we propose a mathematical programming model and solution approaches that take into account costs with own and chartered vehicles, multiple deliverymen, time windows in customers, compatibility of vehicles and customers, time limitations for the circulation of large vehicles in city...

  5. Preparation of Hollow Porous HAP Microspheres as Drug Delivery Vehicles

    Institute of Scientific and Technical Information of China (English)

    WANG Qing; HUANG Wenhai; WANG Deping


    Hollow HAP microspheres in sub-millimeter size were prepared and investigated as a drug delivery vehicle. The LCB (lithium-calcium borate) glass microspheres, which were made through flame spray process, were chosen as precursor for hollow HAP microspheres. The LCB glass microspheres reacted with phosphate buffer (K2HPO4) solution for 5 days at 37 ℃. During the reaction the Ca-P-OH compound precipitated on the surface of LCB glass microspheres and formed porous shells. Then the microspheres turned to be hollow ones with the same diameter as the glass microspheres after LCB glass run out in the chemical reaction. After heat-treated at 600 ℃ for 4 h, the Ca-P-OH compound became HAP, thus the hollow HAP microspheres were produced. The mechanism of forming hollow HAP microspheres through the chemical reaction between phosphate buffer and LCB glass was confirmed by the XRD analysis. The microstructure characteristics of the hollow, porous microspheres were observed by SEM.

  6. Cell-targeting aptamers act as intracellular delivery vehicles. (United States)

    Gopinath, Subash C B; Lakshmipriya, Thangavel; Chen, Yeng; Arshad, M K Md; Kerishnan, Jesinda P; Ruslinda, A R; Al-Douri, Yarub; Voon, C H; Hashim, Uda


    Aptamers are single-stranded nucleic acids or peptides identified from a randomized combinatorial library through specific interaction with the target of interest. Targets can be of any size, from small molecules to whole cells, attesting to the versatility of aptamers for binding a wide range of targets. Aptamers show drug properties that are analogous to antibodies, with high specificity and affinity to their target molecules. Aptamers can penetrate disease-causing microbial and mammalian cells. Generated aptamers that target surface biomarkers act as cell-targeting agents and intracellular delivery vehicles. Within this context, the "cell-internalizing aptamers" are widely investigated via the process of cell uptake with selective binding during in vivo systematic evolution of ligands by exponential enrichment (SELEX) or by cell-internalization SELEX, which targets cell surface antigens to be receptors. These internalizing aptamers are highly preferable for the localization and functional analyses of multiple targets. In this overview, we discuss the ways by which internalizing aptamers are generated and their successful applications. Furthermore, theranostic approaches featuring cell-internalized aptamers are discussed with the purpose of analyzing and diagnosing disease-causing pathogens.

  7. An approximation algorithm for the pickup and delivery vehicle routing problem on trees


    Katoh, Naoki; Yano, Taihei


    This paper presents an approximation algorithm for a vehicle routing problem on a tree-shaped network with a single depot where there are two types of demands, pickup demand and delivery demand. Customers are located on nodes of the tree, and each customer has a positive demand of pickup and/or delivery. Demands of customers are served by a fleet of identical vehicles with unit capacity. Each vehicle can serve pickup and delivery demands. It is assumed that the demand of a customer is splitta...

  8. Vehicle Routing Algorithms for Local Delivery at Naval Supply Centers. (United States)


    the purpose of selecting a vehicle routing algorithm that can be automated. This investigation led the author to a survey of " vehicle routing problem " (also...the vehicle routing problem model is described and solution techniques are sur- veyed. Additionally, computational experience that operations...researchers have had with these solution techniques is pre- sented. There are several classical and theoretical problems related to the vehicle routing problem . These

  9. Rheological characterization of xanthan gum and hydroxypropylmethyl cellulose with respect to controlled-release drug delivery. (United States)

    Talukdar, M M; Vinckier, I; Moldenaers, P; Kinget, R


    It has been observed previously that xanthan gum (XG) and hydroxypropylmethyl cellulose (HPMC) show different drug release behavior. In order to clarify these findings, the rheological properties of both polymers have been determined by oscillatory as well as by steady shear measurements. Aqueous solutions of 4 and 7% (w/w) polymer have been used to simulate the outer surface of a hydrated tablet. The dynamic moduli, i.e., storage modulus (G') and loss modulus (G") of the two polymers have been determined in pure water and USP phosphate buffer pH 7.4 at different dilutions. In this concentration range XG solution exhibits "gel-like" behavior, while HPMC behaves as a typical polymer solution. These findings are quite consistent with the reported higher ability of XG matrices to retard drug release than HPMC matrices for controlled-release formulation. The effects of differences in drug solubility and acidity, as well as the addition of lactose, and of the ionic strength of the medium on the rheological properties of XG and HPMC solutions have been studied in detail. Among these parameters, only the salt concentration exerts an enhancing effect on both moduli of XG, while no detectable influence on HPMC solution could be observed.

  10. Cyclic delivery-scheduling problem with synchronization of vehicles\\' arrivals at logistic centers

    Directory of Open Access Journals (Sweden)

    Katarzyna Zofia Gdowska


    Full Text Available Background: In this paper a cyclic delivery-scheduling problem with vehicles serving fixed routes is presented. Each vehicle is assigned to one route to which some manufacturers' warehouses and logistics centers belong. A vehicle is to be loaded at a manufacturer's warehouse, then to deliver goods to a logistics center and may be also loaded there with other goods and to transport them to the next node along the route. One logistic center belongs to several routes, so the goods delivered by one vehicle may continue their journey by another truck. For every route the frequency of the vehicle is fixed and known. The objective here is to obtain such synchronization of vehicles arrivals in logistics centers, so that it is possible to organize their arrivals in repeatable blocks. Methods: In the paper the cyclic delivery-scheduling problem with vehicles serving fixed routes is formulated as a MIP model. Due to the fixed routes and desirable synchronization of vehicles arrivals in shared points this problem seems to be similar to the public transit network timetabling problem. Because of that the model presented here was based on a model dedicated to the public transit network timetabling problem, where optimization criterion was to maximize synchronization of vehicles' arrivals at the shared nodes. Results: Mixed integer programming model was employed for solving several cases of cyclic delivery-scheduling problem with vehicles serving fixed routes. Computational experiments are reported and obtained results are presented. Conclusions: The mixed integer programming model for the cyclic delivery-scheduling problem with synchronization of vehicles arrivals at logistic centers presented in this paper can be utilized for generating schedules for a group of vehicles serving fixed long routes. It may result in reducing total operational cost related to this group of vehicles as well as in reducing the goods travel time from the place of origin to their

  11. Nanoclays for polymer nanocomposites, paints, inks, greases and cosmetics formulations, drug delivery vehicle and waste water treatment

    Indian Academy of Sciences (India)

    Hasmukh A Patel; Rajesh S Somani; Hari C Bajaj; Raksh V Jasra


    An overview of nanoclays or organically modified layered silicates (organoclays) is presented with emphasis placed on the use of nanoclays as the reinforcement phase in polymer matrices for preparation of polymer/layered silicates nanocomposites, rheological modifier for paints, inks and greases, drug delivery vehicle for controlled release of therapeutic agents, and nanoclays for industrial waste water as well as potable water treatment to make further step into green environment. A little amount of nanoclay can alter the entire properties of polymers, paints, inks and greases to a great extent by dispersing 1nm thick layered silicate throughout the matrices. The flexibility of interlayer spacing of layered silicates accommodates therapeutic agents which can later on be released to damaged cell. Because the release of drugs in drug-intercalated layered materials is controllable, these new materials have a great potential as a delivery host in the pharmaceutical field. The problem of clean water can be solved by treating industrial and municipal waste water with organoclays in combination with other sorbents like activated carbon and alum. Organoclays have proven to be superior to any other water treatment technology in applications where the water to be treated contains substantial amounts of oil and grease or humic acid.

  12. Studies on rheology and microbiological evaluation of hydrotropically gelled starch as topical vehicle for terbinafine hydrochloride

    Directory of Open Access Journals (Sweden)

    Rao Kovur


    Full Text Available The present study was aimed for the development and evaluation of hydrotropic starch gels of terbinafine hydrochloride which is an allylamine derivative of antifungal agent was formulated by using corn starch and sodium salicylate as hydrotropic salt. The gels were prepared in presence and absence of propylene glycol. The prepared gels were evaluated for in vitro drug release, rheological behavior and microbial studies. The degree of increase in the drug diffusion was found to be in order corn starch gel with propylene glycol was greater than corn starch gel without propylene glycol. The microbial studies were carried out in soya bean casein digest medium with Candida albicans as test organisms and were found to be 22.86 ± 0.58 and 20.22 ± 0.65 mm for TCSG (IV and TCS (III, respectively. All the gels exhibited shear thinning. The rheogram indicated that the gel systems are pseudoplastic and exhibited thixotropy. The added propylene glycol has not appreciably altered the apparent viscosity values.

  13. Drug Delivery Using Oral Vehicles: Controlled Release in the GI-tract


    Sæther, Maren


    Oral delivery is considered a convenient route for administration of pharmaceuticals. Great effort has been made to optimize oral delivery vehicles to increase the bioavailability of the pharmaceutical, and enhance patient compliance to ease swallowing. Emulsion-based gelled matrices have shown promising features as delivery systems. They are soft chewable matrices that are easy to swallow, and have the ability to entrap the pharmaceutical, providing prolonged, and controlled release to avoid...

  14. Nanoemulsions as vehicles for transdermal delivery of glycyrrhizin

    Directory of Open Access Journals (Sweden)

    Ranjit Kumar Harwansh


    Full Text Available The present investigation aims to evaluate an isotropic and thermodynamically stable nanoemulsion formulation for transdermal delivery of glycyrrhizin (GZ, with minimum surfactant and cosurfactant (Smix concentrations that could improve its solubility, permeation enhancement, and stability. Pseudo-ternary phase diagrams were developed and various nanoemulsion formulations were prepared using soyabean oil as oil, Span 80, Brij 35 as a surfactant and isopropyl alcohol as a cosurfactant. Nanoemulsion formulations that passed the thermodynamic stability tests were characterized for pH, viscosity and droplet size using a transmission electron microscopy. The transdermal ability of glycyrrhizin through human cadaver skin was determined using Franz diffusion cells. The in vitro skin permeation profile of the optimized nanoemulsion formulation (NE2 was compared to that of conventional gel. A significant increase in permeability parameters such as steady-state flux (Jss and permeability coefficient (Kp was observed in the optimized nanoemulsion formulation (NE2, which consisted of 1% wt/wt of mono ammonium glycyrrhizinate (MAG, 32.4% Span 80, 3.7% Brij 35, 10% isopropyl alcohol, 46.5% soyabean oil and 6.4% distilled water. No obvious skin irritation was observed for the studied nanoemulsion formulation (NE2 or the gel. The results indicated that nanoemulsions are promising vehicles for transdermal delivery of glycyrrhizin through human cadaver skin, without the use of additional permeation enhancers, because excipients of nanoemulsions act as permeation enhancers themselves.O objetivo da investigação é avaliar uma nanoemulsão isotrópica termodinamicamente estável para a administração transdérmica da glicirrizina (GZ, com concentrações mínimas de tensoativo e co-tensoativo (Smix, que poderiam melhorar a sua solubilidade, a permeação e a estabilidade. Os diagramas pseudo-ternários de fase foram desenvolvidos e diversas nanoemulsões foram

  15. Protein nanoparticle: A unique system as drug delivery vehicles

    African Journals Online (AJOL)



    . ... contributions in the field of protein nanoparticles used as drug delivery systems. .... tic guidance. ..... response of cytoskeletal organization and adhesion ..... Helicobacter Pylori Effect of Mucoadhesive Nanoparticles Bearing.

  16. Single-Commodity Vehicle Routing Problem with Pickup and Delivery Service

    Directory of Open Access Journals (Sweden)

    Goran Martinovic


    Full Text Available We present a novel variation of the vehicle routing problem (VRP. Single commodity cargo with pickup and delivery service is considered. Customers are labeled as either cargo sink or cargo source, depending on their pickup or delivery demand. This problem is called a single commodity vehicle routing problem with pickup and delivery service (1-VRPPD. 1-VRPPD deals with multiple vehicles and is the same as the single-commodity traveling salesman problem (1-PDTSP when the number of vehicles is equal to 1. Since 1-VRPPD specializes VRP, it is hard in the strong sense. Iterative modified simulated annealing (IMSA is presented along with greedy random-based initial solution algorithm. IMSA provides a good approximation to the global optimum in a large search space. Experiment is done for the instances with different number of customers and their demands. With respect to average values of IMSA execution times, proposed method is appropriate for practical applications.

  17. Food Delivery System with the Utilization of Vehicle Using Geographical Information System (GIS) and A Star Algorithm (United States)

    Siregar, B.; Gunawan, D.; Andayani, U.; Sari Lubis, Elita; Fahmi, F.


    Food delivery system is one kind of geographical information systems (GIS) that can be applied through digitation process. The main case in food delivery system is the way to determine the shortest path and food delivery vehicle movement tracking. Therefore, to make sure that the digitation process of food delivery system can be applied efficiently, it is needed to add shortest path determination facility and food delivery vehicle tracking. This research uses A Star (A*) algorithm for determining shortest path and location-based system (LBS) programming for moving food delivery vehicle object tracking. According to this research, it is generated the integrated system that can be used by food delivery driver, customer, and administrator in terms of simplifying the food delivery system. Through the application of shortest path and the tracking of moving vehicle, thus the application of food delivery system in the scope of geographical information system (GIS) can be executed.


    Directory of Open Access Journals (Sweden)

    José Ferreira de Souza Neto

    Full Text Available ABSTRACT This work addresses a vehicle routing problem that aims at representing delivery operations of large volumes of products in dense urban areas. Inspired by a case study in a drinks producer and distributor, we propose a mathematical programming model and solution approaches that take into account costs with own and chartered vehicles, multiple deliverymen, time windows in customers, compatibility of vehicles and customers, time limitations for the circulation of large vehicles in city centers and multiple daily trips. Results with instances based on real data provided by the company highlight the potential of applicability of some of the proposed methods.

  19. Multi-depot Vehicle Routing Problem with Pickup and Delivery Requests (United States)

    Sombuntham, Pandhapon; Kachitvichyanukul, Voratas


    This paper considers a multi-depot vehicle routing problem with pickup and delivery requests. In the problem of interest, each location may have goods for both pickup and delivery with multiple delivery locations that may not be the depots. These characteristics are quite common in industrial practice. A particle swarm optimization algorithm with multiple social learning structures is proposed for solving the practical case of multi-depot vehicle routing problem with simultaneous pickup and delivery and time window. A new decoding procedure is implemented using the PSO class provided in the ETLib object library. Computational experiments are carried out using the test instances for the pickup and delivery problem with time windows (PDPTW) as well as a newly generated instance. The preliminary results show that the proposed algorithm is able to provide good solutions to most of the test problems.

  20. Recent progress in development of siRNA delivery vehicles for cancer therapy. (United States)

    Kim, Hyun Jin; Kim, Ahram; Miyata, Kanjiro; Kataoka, Kazunori


    Recent progress in RNA biology has broadened the scope of therapeutic targets of RNA drugs for cancer therapy. However, RNA drugs, typically small interfering RNAs (siRNAs), are rapidly degraded by RNases and filtrated in the kidney, thereby requiring a delivery vehicle for efficient transport to the target cells. To date, various delivery formulations have been developed from cationic lipids, polymers, and/or inorganic nanoparticles for systemic delivery of siRNA to solid tumors. This review describes the current status of clinical trials related to siRNA-based cancer therapy, as well as the remaining issues that need to be overcome to establish a successful therapy. It, then introduces various promising design strategies of delivery vehicles for stable and targeted siRNA delivery, including the prospects for future design.

  1. Exosomes as therapeutic drug carriers and delivery vehicles across biological membranes: current perspectives and future challenges. (United States)

    Ha, Dinh; Yang, Ningning; Nadithe, Venkatareddy


    Exosomes are small intracellular membrane-based vesicles with different compositions that are involved in several biological and pathological processes. The exploitation of exosomes as drug delivery vehicles offers important advantages compared to other nanoparticulate drug delivery systems such as liposomes and polymeric nanoparticles; exosomes are non-immunogenic in nature due to similar composition as body׳s own cells. In this article, the origin and structure of exosomes as well as their biological functions are outlined. We will then focus on specific applications of exosomes as drug delivery systems in pharmaceutical drug development. An overview of the advantages and challenges faced when using exosomes as a pharmaceutical drug delivery vehicles will also be discussed.

  2. Systems Analysis and Structural Design of an Unpressurized Cargo Delivery Vehicle (United States)

    Wu, K. Chauncey; Cruz, Jonathan N.; Antol, Jeffrey; Sasamoto, Washito A.


    The International Space Station will require a continuous supply of replacement parts for ongoing maintenance and repair after the planned retirement of the Space Shuttle in 2010. These parts are existing line-replaceable items collectively called Orbital Replacement Units, and include heavy and oversized items such as Control Moment Gyroscopes and stowed radiator arrays originally intended for delivery aboard the Space Shuttle. Current resupply spacecraft have limited to no capability to deliver these external logistics. In support of NASA's Exploration Systems Architecture Study, a team at Langley Research Center designed an Unpressurized Cargo Delivery Vehicle to deliver bulk cargo to the Space Station. The Unpressurized Cargo Delivery Vehicle was required to deliver at least 13,200 lbs of cargo mounted on at least 18 Flight Releasable Attachment Mechanisms. The Crew Launch Vehicle design recommended in the Exploration Systems Architecture Study would be used to launch one annual resupply flight to the International Space Station. The baseline vehicle design developed here has a cargo capacity of 16,000 lbs mounted on up to 20 Flight Releasable Attachment Mechanisms. Major vehicle components are a 5.5m-diameter cargo module containing two detachable cargo pallets with the payload, a Service Module to provide propulsion and power, and an aerodynamic nose cone. To reduce cost and risk, the Service Module is identical to the one used for the Crew Exploration Vehicle design.

  3. Macrophage mannose receptor-specific gene delivery vehicle for macrophage engineering. (United States)

    Ruan, Gui-Xin; Chen, Yu-Zhe; Yao, Xing-Lei; Du, Anariwa; Tang, Gu-Ping; Shen, You-Qing; Tabata, Yasuhiko; Gao, Jian-Qing


    Macrophages are the most plastic cells in the hematopoietic system and they exhibit great functional diversity. They have been extensively applied in anti-inflammatory, anti-fibrotic and anti-cancer therapies. However, the application of macrophages is limited by the efficiency of their engineering. The macrophage mannose receptor (MMR, CD206), a C-type lectin receptor, is ubiquitously expressed on macrophages and has a high affinity for mannose oligosaccharides. In the present study, we developed a novel non-viral vehicle with specific affinity for MMR. Mannan was cationized with spermine at a grafted ratio of ∼12% to deliver DNA and was characterized as a stable system for delivery. This spermine-mannan (SM)-based delivery system was evaluated as a biocompatible vehicle with superior transfection efficiency on murine macrophages, up to 28.5-fold higher than spermine-pullulan, 11.5-fold higher than polyethylenimine and 3.0-fold higher than Lipofectamine™ 2000. We confirmed that the SM-based delivery system for macrophages transfection was MMR-specific and we described the intracellular transport of the delivery system. To our knowledge, this is the first study using SM to demonstrate a mannose receptor-specific gene delivery system, thereby highlighting the potential of a novel specific non-viral delivery vehicle for macrophage engineering.

  4. HDL as a drug and nucleic acid delivery vehicle

    Directory of Open Access Journals (Sweden)

    Andras G Lacko


    Full Text Available This review is intended to evaluate the research findings and potential clinical applications of drug transport systems, developed based on the concepts of the structure/function and physiological role(s of high density lipoprotein=type nanoparticles. These macromolecules provide targeted transport of cholesteryl esters (a highly lipophilic payload in their natural/physiological environment. The property of accommodating highly water insoluble constituents in their core region enables HDL type nanoparticles to effectively transport hydrophobic drugs upon intravenous administration. Even though the application of reconstituted HDL in the treatment of a number of diseases is reviewed, the primary focus is on the application of HDL type drug delivery agents in cancer chemotherapy. The use of both native and synthetic HDL as drug delivery agents are compared to evaluate their respective potentials for commercial and clinical development. The current status and future perspectives for HDL type nanoparticles are discussed, including current obstacles and future applications in therapeutics.

  5. Capsosomes as Long-Term Delivery Vehicles for Protein Therapeutics. (United States)

    Maina, James W; Richardson, Joseph J; Chandrawati, Rona; Kempe, Kristian; van Koeverden, Martin P; Caruso, Frank


    We report the preparation of polymer capsules containing liposomal subcompartments, termed capsosomes, and their ability for the sustained delivery of protein therapeutics. Capsosomes were formed through the layer-by-layer (LbL) assembly of polymers and protein-loaded liposomes, followed by the formation of a capsule membrane based on disulfide cross-linked poly(methacrylic acid). The loading capacities of a model cargo (lysozyme) and brain-derived neurotrophic factor (BDNF), an important neurotrophin that has significant physiological functions on the nervous system, were determined, and the long-term release kinetics of the proteins was investigated in simulated physiological conditions. The capsosomes exhibited protein loading and release behavior that can be tuned by the lipid composition of the liposomal compartments, where inclusion of anionic lipids resulted in enhanced protein loading and slower release over the course of 80 days. These findings highlight the potential of capsosomes for the long-term delivery of protein therapeutics.

  6. Polyphosphazenes: Multifunctional, Biodegradable Vehicles for Drug and Gene Delivery

    Directory of Open Access Journals (Sweden)

    Ian Teasdale


    Full Text Available Poly[(organophosphazenes] are a unique class of extremely versatile polymers with a range of applications including tissue engineering and drug delivery, as hydrogels, shape memory polymers and as stimuli responsive materials. This review aims to divulge the basic principles of designing polyphosphazenes for drug and gene delivery and portray the huge potential of these extremely versatile materials for such applications. Polyphosphazenes offer a number of distinct advantages as carriers for bioconjugates; alongside their completely degradable backbone, to non-toxic degradation products, they possess an inherently and uniquely high functionality and, thanks to recent advances in their polymer chemistry, can be prepared with controlled molecular weights and narrow polydispersities, as well as self-assembled supra-molecular structures. Importantly, the rate of degradation/hydrolysis of the polymers can be carefully tuned to suit the desired application. In this review we detail the recent developments in the chemistry of polyphosphazenes, relevant to drug and gene delivery and describe recent investigations into their application in this field.

  7. Procurement and Delivery of Joint Service Armor Protected Vehicles (United States)


    vehicles should not ha ve bcen compared to each othcr 0 1’ to a singlc IG E. F8Jl 8FFISMb l!IS6 8PlbY 29 An M S orti eial stated that thc IGCE was thi s casc. Adcquate competition can be cxpccted to result in fail’ and rcasonable contract prices. However, an M S orti cial statcd that comments concerning the fa ir and reasonable con tract price determination from the Ortiee of Defense Procurement Acq ui sit ion Po li cy (D PAP

  8. Penetrating the Blood-Brain Barrier: Promise of Novel Nanoplatforms and Delivery Vehicles. (United States)

    Ali, Iqbal Unnisa; Chen, Xiaoyuan


    Multifunctional nanoplatforms combining versatile therapeutic modalities with a variety of imaging options have the potential to diagnose, monitor, and treat brain diseases. The promise of nanotechnology can only be realized by the simultaneous development of innovative brain-targeting delivery vehicles capable of penetrating the blood-brain barrier without compromising its structural integrity.

  9. Evaluation of aftermarket fuel delivery systems for natural gas and LPG vehicles

    Energy Technology Data Exchange (ETDEWEB)

    Willson, B. (Colorado State Univ., Fort Collins, CO (United States))


    This study was designed to evaluate the effectiveness of aftermarket fuel delivery systems for vehicles fueled by compressed natural gas (CNG) and liquefied petroleum gas (LPG). Most of the CNG and LPG vehicles studied were converted to the alternative fuel after purchase. There are wide variations in the quality of the conversion hardware and the installation. This leads to questions about the overall quality of the converted vehicles, in terms of emissions, safety, and performance. There is a considerable body of emissions data for converted light-duty vehicles, and a smaller amount for medium- and heavy-duty vehicles. However, very few of these data involve real world conditions, and there is growing concern about in-use emissions. This report also attempts to assess factors that could allow in-use emissions to vary from the best-case'' results normally reported. The study also addresses issues of fuel supply, fuel composition, performance, safety, and warranty waivers. The report is based on an extensive literature and product survey and on the author's experience with fuel delivery systems for light-duty vehicles.

  10. Evaluation of aftermarket fuel delivery systems for natural gas and LPG vehicles

    Energy Technology Data Exchange (ETDEWEB)

    Willson, B. [Colorado State Univ., Fort Collins, CO (United States)


    This study was designed to evaluate the effectiveness of aftermarket fuel delivery systems for vehicles fueled by compressed natural gas (CNG) and liquefied petroleum gas (LPG). Most of the CNG and LPG vehicles studied were converted to the alternative fuel after purchase. There are wide variations in the quality of the conversion hardware and the installation. This leads to questions about the overall quality of the converted vehicles, in terms of emissions, safety, and performance. There is a considerable body of emissions data for converted light-duty vehicles, and a smaller amount for medium- and heavy-duty vehicles. However, very few of these data involve real world conditions, and there is growing concern about in-use emissions. This report also attempts to assess factors that could allow in-use emissions to vary from the ``best-case`` results normally reported. The study also addresses issues of fuel supply, fuel composition, performance, safety, and warranty waivers. The report is based on an extensive literature and product survey and on the author`s experience with fuel delivery systems for light-duty vehicles.

  11. Structural Design and Analysis of Un-pressurized Cargo Delivery Vehicle (United States)

    Martinovic, Zoran N.


    As part of the Exploration Systems Architecture Study, NASA has defined a family of vehicles to support lunar exploration and International Space Station (ISS) re-supply missions after the Shuttle s retirement. The Un-pressurized Cargo Delivery Vehicle (UCDV) has been envisioned to be an expendable logistics delivery vehicle that would be used to deliver external cargo to the ISS. It would be launched on the Crew Launch Vehicle and would replace the Crew Exploration Vehicle. The estimated cargo would be the weight of external logistics to the ISS. Determining the minimum weight design of the UCDV during conceptual design is the major issue addressed in this paper. This task was accomplished using a procedure for rapid weight estimation that was based on Finite Element Analysis and sizing of the vehicle by the use of commercially available codes. Three design concepts were analyzed and their respective weights were compared. The analytical structural weight was increased by a factor to account for structural elements that were not modeled. Significant reduction in weight of a composite design over metallic was achieved for similar panel concepts.

  12. Mathematical model of microbicidal flow dynamics and optimization of rheological properties for intra-vaginal drug delivery: Role of tissue mechanics and fluid rheology. (United States)

    Anwar, Md Rajib; Camarda, Kyle V; Kieweg, Sarah L


    Topically applied microbicide gels can provide a self-administered and effective strategy to prevent sexually transmitted infections (STIs). We have investigated the interplay between vaginal tissue elasticity and the yield-stress of non-Newtonian fluids during microbicide deployment. We have developed a mathematical model of tissue deformation driven spreading of microbicidal gels based on thin film lubrication approximation and demonstrated the effect of tissue elasticity and fluid yield-stress on the spreading dynamics. Our results show that both elasticity of tissue and yield-stress rheology of gel are strong determinants of the coating behavior. An optimization framework has been demonstrated which leverages the flow dynamics of yield-stress fluid during deployment to maximize retention while reaching target coating length for a given tissue elasticity.

  13. A new memetic algorithm for solving split delivery vehicle routing problem

    Directory of Open Access Journals (Sweden)

    Ali Bozorgi-Amiri


    Full Text Available Split delivery vehicle routing problem is one of the traditional types of routing problems in which the demand of different points can be divided among vehicles and the objective is to minimize the path length, which vehicles travel. In this paper, fuel cost of vehicles which is assumed to be dependent on their traveled path and load is considered as the objective functions. Namely, the cost of the consumed fuel is proportionate to the unit of load carried per unit of distance. In order to solve the proposed model a new memetic algorithm is developed which has two rows. The performance of the proposed algorithm for 21 standard problems is compared with the optimum solutions obtained from mathematical programming standard solver and the solutions of the same algorithm with single row solution representation. The results express the efficiency of developed algorithm.

  14. Time Dependent Heterogeneous Vehicle Routing Problem for Catering Service Delivery Problem (United States)

    Azis, Zainal; Mawengkang, Herman


    The heterogeneous vehicle routing problem (HVRP) is a variant of vehicle routing problem (VRP) which describes various types of vehicles with different capacity to serve a set of customers with known geographical locations. This paper considers the optimal service deliveries of meals of a catering company located in Medan City, Indonesia. Due to the road condition as well as traffic, it is necessary for the company to use different type of vehicle to fulfill customers demand in time. The HVRP incorporates time dependency of travel times on the particular time of the day. The objective is to minimize the sum of the costs of travelling and elapsed time over the planning horizon. The problem can be modeled as a linear mixed integer program and we address a feasible neighbourhood search approach to solve the problem.

  15. PEGylated Dendrimers as Drug Delivery Vehicles for the Photosensitizer Silicon Phthalocyanine Pc 4 for Candidal Infections. (United States)

    Hutnick, Melanie A; Ahsanuddin, Sayeeda; Guan, Linna; Lam, Minh; Baron, Elma D; Pokorski, Jonathan K


    Fungi account for billions of infections worldwide. The second most prominent causative agent for fungal infections is Candida albicans (C. albicans). As strains of fungi become resistant to antifungal medications, new treatment modalities must be investigated to combat these infections. One approach is to employ photodynamic therapy (PDT). PDT utilizes a photosensitizer, light, and cellular O2 to produce reactive oxygen species (ROS), which then induce oxidative stress resulting in apoptosis. Silicon phthalocyanine Pc 4 is a photosensitizer that has exhibited success in clinical trials for a myriad of skin diseases. The hydrophobic nature of Pc 4, however, poses significant formulation and delivery challenges in the use of this therapy. To mitigate these concerns, a drug delivery vehicle was synthesized to better formulate Pc 4 into a viable PDT agent for treating fungal infections. Utilizing poly(amidoamine) dendrimers as the framework for the vehicle, ∼13% of the amine chain ends were PEGylated to promote water solubility and deter nonspecific adsorption. In vitro studies with C. albicans demonstrate that the potency of Pc 4 was not hindered by the dendrimer vehicle. Encapsulated Pc 4 was able to effectively generate ROS and obliterate fungal pathogens upon photoactivation. The results presented within describe a nanoparticulate delivery vehicle for Pc 4 that readily kills drug-resistant C. albicans and eliminates solvent toxicity, thus, improving formulation characteristics for the hydrophobic photosensitizer.

  16. Molecular Imaging of Biological Gene Delivery Vehicles for Targeted Cancer Therapy: Beyond Viral Vectors

    Energy Technology Data Exchange (ETDEWEB)

    Min, Jung Joon; Nguyen, Vu H. [Chonnam National University Medical School, Gwangju (Korea, Republic of); Gambhir, Sanjiv S. [Stanford University, California(United States)


    Cancer persists as one of the most devastating diseases in the world. Problems including metastasis and tumor resistance to chemotherapy and radiotherapy have seriously limited the therapeutic effects of present clinical treatments. To overcome these limitations, cancer gene therapy has been developed over the last two decades for a broad spectrum of applications, from gene replacement and knockdown to vaccination, each with different requirements for gene delivery. So far, a number of genes and delivery vectors have been investigated, and significant progress has been made with several gene therapy modalities in clinical trials. Viral vectors and synthetic liposomes have emerged as the vehicles of choice for many applications. However, both have limitations and risks that restrict gene therapy applications, including the complexity of production, limited packaging capacity, and unfavorable immunological features. While continuing to improve these vectors, it is important to investigate other options, particularly nonarrival biological agents such as bacteria, bacteriophages, and bacteria-like particles. Recently, many molecular imaging techniques for safe, repeated, and high-resolution in vivo imaging of gene expression have been employed to assess vector-mediated gene expression in living subjects. In this review, molecular imaging techniques for monitoring biological gene delivery vehicles are described, and the specific use of these methods at different steps is illustrated. Linking molecular imaging to gene therapy will eventually help to develop novel gene delivery vehicles for preclinical study and support the development of future human applications.

  17. Mesoporous silica nanoparticles as a biomolecule delivery vehicle in plants

    Energy Technology Data Exchange (ETDEWEB)

    Hussain, Hashmath I., E-mail: [Deakin University, Centre for Chemistry and Biotechnology, School of Life and Environmental Sciences (Australia); Yi, Zhifeng [Deakin University, Institute for Frontier Materials (Australia); Rookes, James E. [Deakin University, Centre for Chemistry and Biotechnology, School of Life and Environmental Sciences (Australia); Kong, Lingxue X. [Deakin University, Institute for Frontier Materials (Australia); Cahill, David M. [Deakin University, Centre for Chemistry and Biotechnology, School of Life and Environmental Sciences (Australia)


    We report the uptake by wheat, lupin and Arabidopsis of mesoporous silica nanoparticles functionalised with amine cross-linked fluorescein isothiocyanate (MSN-APTES-FITC). The preparation of these particles at room temperature enabled the synthesis of 20 nm particles that contained a network of interconnected pores around 2 nm in diameter. The uptake and distribution of these nanoparticles were examined during seed germination, in roots of plants grown in a hydroponic system and in whole leaves and roots of plants via vacuum infiltration. The nanoparticles did not affect seed germination in lupin and there was no phytotoxicity. Following germination of wheat and lupin grown in a nutrient solution containing nanoparticles, they were found within cells and cell walls of the emerging root and in the vascular transport elements, the xylem, and in other associated cells. In leaves and roots of Arabidopsis the nanoparticles were found, following vacuum infiltration of whole seedlings, to be taken up by the entire leaf and they were principally found in the intercellular spaces of the mesophyll but also throughout much of the root system. We propose that MSNs could be used as a novel delivery system for small molecules in plants.

  18. Drug Delivery Vehicles Based on Albumin-Polymer Conjugates. (United States)

    Jiang, Yanyan; Stenzel, Martina


    Albumin has been a popular building block to create nanoparticles for drug delivery purposes. The performance of albumin as a drug carrier can be enhanced by combining protein with polymers, which allows the design of carriers to encompass a broader spectrum of drugs while features unique to synthetic polymers such as stimuli-responsiveness are introduced. Nanoparticles based on polymer-albumin hybrids can be divided into two classes: one that carries album as a bioactive surface coating and the other that uses albumin as biocompatible, although nonbioactive, building block. Nanoparticles with bioactive albumin surface coating can either be prepared by self-assembly of albumin-polymer conjugates or by postcoating of existing nanoparticles with albumin. Albumin has also been used as building block, either in its native or denatured form. Existing albumin nanoparticles are coated with polymers, which can influence the degradation of albumin or impact on the drug release. Finally, an alternative way of using albumin by denaturing the protein to generate a highly functional chain, which can be modified with polymer, has been presented. These albumin nanoparticles are designed to be extremely versatile so that they can deliver a wide variety of drugs, including traditional hydrophobic drugs, metal-based drugs and even therapeutic proteins and siRNA.

  19. Extracellular Vesicles as Drug Delivery Vehicles for Rheumatoid Arthritis. (United States)

    Kim, Il-Kwon; Kim, Sun-Hyun; Choi, Seong-Mi; Youn, Byung-Soo; Kim, Han-Soo


    Rheumatoid arthritis (RA) is a chronic, systemic and progressive autoimmune disease of connective tissues common in middle age. Dysregulation of the tissue homeostasis involving inflammation is the hallmark of disease pathogenesis, inducing autoimmune insults that frequently lead to permanent disability. Although the advent of immunosuppressive and anti-inflammatory drugs and, more recently, pathogenic TNF-TNF-R axis-targeting biologics significantly delayed progressive joint destruction with significant reduction of disability and physical improvement, a large proportion of RA patients failed to respond to the treatment. In this regard, mesenchymal stem/stromal cells (MSC) are particularly attractive to the refractory patients to the pharmacologic intervention for their immunosuppressive/anti-inflammatory capacity as well as tissue reparative and/or regenerative potential. Local or systemic delivery of MSCs led to promising results in preclinical as well as in clinical studies of RA and thus proposing that these cells can be further exploited for their therapeutic application in RA and other degenerative connective tissue diseases. Mechanistically, paracrine factors appear to be the main contributors of MSC-mediated tissue regeneration in a number of preclinical and clinical studies rather than direct tissue cell replacement. More recently, extracellular vesicles (EVs) released from MSCs emerged as key paracrine messengers that can also participate in the healing process through influencing the local microenvironment with anti-inflammatory effects. It is highly likely that the use of these EVs becomes beneficial in the treatment of RA. Yet, identification of key components involved in the regenerative process needs to be assessed for developing efficient MSC-based strategy of RA treatment.

  20. An Optimization Model for the Vehicle Routing Problem in Multi-product Frozen Food Delivery

    Directory of Open Access Journals (Sweden)

    Y. Zhang


    Full Text Available This paper addresses a vehicle scheduling problem encountered in the cold chain logistics of the frozen food delivery industry. Unlike the single product delivery scenario, we propose an optimization model that manages the delivery of a variety of products. In this scenario, a set of customers make requests for a variety of frozen foods which are being loaded together. The objective is to find the routes that represent the minimum delivery cost for a fleet of identical vehicles that, departing from a depot, visiting all customers only once and returning to the depot. The delivery cost includes the transportation cost, the cost of refrigeration, the penalty cost and cargo damage cost based on the characteristics of different frozen food products. Apart from the usual constraints of time windows and loading weight, the study also takes into account the constraints of loading volume related to the unit volume of different frozen foods. We then propose a Genetic Algorithm (GA method for the model. Computational tests with real data from a case validate the feasibility and rationality of the model and show the efficient combinations of parameter values of the GA method.

  1. Lactic acid bacteria as mucosal delivery vehicles: a realistic therapeutic option. (United States)

    Wang, Miao; Gao, Zeqian; Zhang, Yongguang; Pan, Li


    Recombinant lactic acid bacteria (LAB), in particular lactococci and lactobacilli, have gained increasing interest as mucosal delivery vehicles in recent years. With the development of mucosal vaccines, studies on LAB expression systems have been mainly focused on the generation of genetic tools for antigen expression in different locations. Recombinant LAB show advantages in a wide range of aspects over other mucosal delivery systems and represent an attractive candidate for the delivery of therapeutic and prophylactic molecules in different applications. Here, we review the recent data on the use of recombinant LAB as mucosal delivery vectors and the associated health benefits, including the prevention and treatment of inflammatory bowel diseases (IBDs), autoimmune disorders, and infections by pathogenic microorganisms from mucosal surfaces. In addition, we discuss the use of LAB as vehicles to deliver DNA directly to eukaryotic cells. Researches from the last 5 years demonstrate that LAB as vectors for mucosal delivery of therapeutic molecules seem to be a realistic therapeutic option both in human and animal diseases.

  2. An examination of the rheological and mucoadhesive properties of poly(acrylic acid) organogels designed as platforms for local drug delivery to the oral cavity. (United States)

    Jones, David S; Muldoon, Brendan C O; Woolfson, A David; Sanderson, F Dominic


    This study examined the rheological/mucoadhesive properties of poly(acrylic acid) PAA organogels as platforms for drug delivery to the oral cavity. Organogels were prepared using PAA (3%, 5%, 10% w/w) dissolved in ethylene glycol (EG), propylene glycol (PG), 1,3-propylene glycol (1,3-PG), 1,5-propanediol (1,5-PD), polyethylene glycol 400 (PEG 400), or glycerol. All organogels exhibited pseudoplastic flow. The increase in storage (G') and loss (G'') moduli of organogels as a function of frequency was minimal, G'' was greater than G'' (at all frequencies), and the loss tangent properties. Enhanced rheological structuring was associated with organogels prepared using glycerol (in particular) and PEG 400 due to their interaction with adjacent carboxylic acid groups on each chain and on adjacent chains. All organogels (with the exception of 1,5-PD) exhibited greater network structure than aqueous PAA gels. Organogel mucoadhesion increased with polymer concentration. Greatest mucoadhesion was associated with glycerol-based formulations, whereas aqueous PAA gels exhibited the lowest mucoadhesion. The enhanced network structure and the excellent mucoadhesive properties of these organogels, both of which may be engineered through choice of polymer concentration/solvent type, may be clinically useful for the delivery of drugs to the oral cavity.

  3. Manned Mars mission Earth-To-Orbit (ETO) delivery and orbit assembly of the manned Mars vehicle (United States)

    Barisa, B.; Solmon, G.


    The initial concepts developed for the in-orbit assembly of a Manned Mars Vehicle and for the Earth-to-Orbit (ETO) delivery of the required hardware and propellant are presented. Two (2) Mars vehicle concepts (all-propulsive and all-aerobrake) and two (2) ETO Vehicle concepts were investigated. Both Mars Vehicle concepts are described in Reference 1, and both ETO Vehicle concepts are described in Reference 2. The all-aerobrake configuration reduces the number of launches and time required to deliver the necessary hardware/propellent to orbit. Use of the larger of the 2 ETO Vehicles (HLLV) further reduces the number of launches and delivery time; however, this option requires a completely new vehicle and supporting facilities.

  4. Hydraulic Hybrid and Conventional Parcel Delivery Vehicles' Measured Laboratory Fuel Economy on Targeted Drive Cycles

    Energy Technology Data Exchange (ETDEWEB)

    Lammert, M. P.; Burton, J.; Sindler, P.; Duran, A.


    This research project compares laboratory-measured fuel economy of a medium-duty diesel powered hydraulic hybrid vehicle drivetrain to both a conventional diesel drivetrain and a conventional gasoline drivetrain in a typical commercial parcel delivery application. Vehicles in this study included a model year 2012 Freightliner P100H hybrid compared to a 2012 conventional gasoline P100 and a 2012 conventional diesel parcel delivery van of similar specifications. Drive cycle analysis of 484 days of hybrid parcel delivery van commercial operation from multiple vehicles was used to select three standard laboratory drive cycles as well as to create a custom representative cycle. These four cycles encompass and bracket the range of real world in-use data observed in Baltimore United Parcel Service operations. The NY Composite cycle, the City Suburban Heavy Vehicle Cycle cycle, and the California Air Resources Board Heavy Heavy-Duty Diesel Truck (HHDDT) cycle as well as a custom Baltimore parcel delivery cycle were tested at the National Renewable Energy Laboratory's Renewable Fuels and Lubricants Laboratory. Fuel consumption was measured and analyzed for all three vehicles. Vehicle laboratory results are compared on the basis of fuel economy. The hydraulic hybrid parcel delivery van demonstrated 19%-52% better fuel economy than the conventional diesel parcel delivery van and 30%-56% better fuel economy than the conventional gasoline parcel delivery van on cycles other than the highway-oriented HHDDT cycle.

  5. Directed transport of bacteria-based drug delivery vehicles: bacterial chemotaxis dominates particle shape. (United States)

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


    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).

  6. Using Gold Nanoparticles as Delivery Vehicles for Targeted Delivery of Chemotherapy Drug Fludarabine Phosphate to Treat Hematological Cancers. (United States)

    Song, Steven; Hao, Yuzhi; Yang, Xiaoyan; Patra, Prabir; Chen, Jie


    Nanotechnology is an emerging paradigm for creating functional nanoscale materials for various biomedical applications. In this study, a new nanotechnology-based drug delivery method was developed using gold nanoparticles (GNPs) as a delivery vehicle to reduce adverse drug side effects. Fludarabine Phosphate is a commercial chemotherapy drug used in cancer treatment, and has ability to kill various cancer cells. KG-1 cell, a type of acute cancer leukemia cell, was selected as a proof-of-concept target in this study. Due to the small size of GNPs, they can help Fludarabine Phosphate enter cancer cells more efficiently and better interfere with DNA synthesis in the cancer cells. To enhance targeting ability, folic acid molecules were also covalently linked to GNPs, resulting in GNP-Fludarabine-folic acid (GNP-F/f). Compared to treatments with GNP-F or drugs on its own (Fludarabine Phosphate), the GNP-F/f achieves much improved cell-killing effects. The UV-Vis spectra results also revealed that the drugs had successfully bonded covalently to the GNPs. The higher cell-killing efficiency of GNP-F/f compared with GNP-Fludarabine (GNP-F) or drugs on their own further validates the effectiveness of both the vectors (GNPs) and folic acid in enhancing the drug delivery to the cancer cells. The MTT viability tests showed that the GNPs had no cytotoxicity.

  7. From structures to functions: insights into exosomes as promising drug delivery vehicles. (United States)

    Ren, Jinghua; He, Wenshan; Zheng, Lifen; Duan, Hongwei


    Exosomes are small membrane vesicles secreted by most cell types, and appear ubiquitously in cell culture supernatants and body fluids. Increasing evidence supports that exosomes play important roles in intercellular communication, both locally and systemically, by transporting their contents such as proteins, lipids and RNAs between cells. Of particular interest for controlled drug delivery is that cell-derived exosomes offer the possibilities of overcoming biological barriers, thereby allowing the incorporated gene and drug to reach targeted tissue, which have been considerable challenges for synthetic carriers. Great research efforts have been dedicated to developing exosome-based drug delivery systems for the treatment of inflammatory diseases, degenerative disorders and cancer. In this review, we will describe the structural and functional properties of exosomes and emphasize current advances in the therapeutic applications of exosomes as drug delivery vehicles, followed by a discussion on current challenges and future perspectives.

  8. Exosomes: Tunable Nano Vehicles for Macromolecular Delivery of Transferrin and Lactoferrin to Specific Intracellular Compartment. (United States)

    Malhotra, Himanshu; Sheokand, Navdeep; Kumar, Santosh; Chauhan, Anoop S; Kumar, Manoj; Jakhar, Priyanka; Boradia, Vishant M; Raje, Chaaya I; Raje, Manoj


    Due to their abundant ubiquitous presence, rapid uptake and increased requirement in neoplastic tissue, the delivery of the iron carrier macromolecules transferrin (Tf) and lactoferrin (Lf) into mammalian cells is the subject of intense interest for delivery of drugs and other target molecules into cells. Utilizing exosomes obtained from cells of diverse origin we confirmed the presence of the multifunctional protein glyceraldehyde-3-phosphate dehydrogenase (GAPDH) which has recently been characterized as a Tf and Lf receptor. Using a combination of biochemical, biophysical and imaging based methodologies, we demonstrate that GAPDH present in exosomes captures Tf and Lf and subsequently effectively delivers these proteins into mammalian cells. Exosome vesicles prepared had a size of 51.2 ± 23.7 nm. They were found to be stable in suspension with a zeta potential (ζ-potential) of -28.16 ± 1.15 mV. Loading of Tf/Lf did not significantly affect ζ-potential of the exosomes. The carrier protein loaded exosomes were able to enhance the delivery of Tf/Lf by 2 to 3 fold in a diverse panel of cell types. Ninety percent of the internalized cargo via this route was found to be specifically delivered into late endosome and lysosomes. We also found exosomes to be tunable nano vehicles for cargo delivery by varying the amount of GAPDH associated with exosome. The current study opens a new avenue of research for efficient delivery of these vital iron carriers into cells employing exosomes as a nano delivery vehicle.

  9. Guar gum solutions for improved delivery of iron particles in porous media (Part 1): Porous medium rheology and guar gum-induced clogging (United States)

    Gastone, Francesca; Tosco, Tiziana; Sethi, Rajandrea


    The present work is the first part of a comprehensive study on the use of guar gum to improve delivery of microscale zero-valent iron particles in contaminated aquifers. Guar gum solutions exhibit peculiar shear thinning properties, with high viscosity in static conditions and lower viscosity in dynamic conditions: this is beneficial both for the storage of MZVI dispersions, and also for the injection in porous media. In the present paper, the processes associated with guar gum injection in porous media are studied performing single-step and multi-step filtration tests in sand-packed columns. The experimental results of single-step tests performed by injecting guar gum solutions prepared at several concentrations and applying different dissolution procedures evidenced that the presence of residual undissolved polymeric particles in the guar gum solution may have a relevant negative impact on the permeability of the porous medium, resulting in evident clogging. The most effective preparation procedure which minimizes the presence of residual particles is dissolution in warm water (60 °C) followed by centrifugation (procedure T60C). The multi-step tests (i.e. injection of guar gum at constant concentration with a step increase of flow velocity), performed at three polymer concentrations (1.5, 3 and 4 g/l) provided information on the rheological properties of guar gum solutions when flowing through a porous medium at variable discharge rates, which mimic the injection in radial geometry. An experimental protocol was defined for the rheological characterization of the fluids in porous media, and empirical relationships were derived for the quantification of rheological properties and clogging with variable injection rate. These relationships will be implemented in the second companion paper (Part II) in a radial transport model for the simulation of large-scale injection of MZVI-guar gum slurries.

  10. Acoustically-active microbubbles conjugated to liposomes: characterization of a proposed drug delivery vehicle. (United States)

    Kheirolomoom, Azadeh; Dayton, Paul A; Lum, Aaron F H; Little, Erika; Paoli, Eric E; Zheng, Hairong; Ferrara, Katherine W


    A new acoustically-active delivery vehicle was developed by conjugating liposomes and microbubbles, using the high affinity interaction between avidin and biotin. Binding between microbubbles and liposomes, each containing 5% DSPE-PEG2kBiotin, was highly dependent on avidin concentration and observed above an avidin concentration of 10 nM. With an optimized avidin and liposome concentration, we measured and calculated as high as 1000 to 10,000 liposomes with average diameters of 200 and 100 nm, respectively, attached to each microbubble. Replacing avidin with neutravidin resulted in 3-fold higher binding, approaching the calculated saturation level. High-speed photography of this new drug delivery vehicle demonstrated that the liposome-bearing microbubbles oscillate in response to an acoustic pulse in a manner similar to microbubble contrast agents. Additionally, microbubbles carrying liposomes could be spatially concentrated on a monolayer of PC-3 cells at the focal point of ultrasound beam. As a result of cell-vehicle contact, the liposomes fused with the cells and internalization of NBD-cholesterol occurred shortly after incubation at 37 degrees C, with internalization of NBD-cholesterol substantially enhanced in the acoustic focus.

  11. A two-stage heuristic method for vehicle routing problem with split deliveries and pickups

    Institute of Scientific and Technical Information of China (English)

    Yong WANG; Xiao-lei MA; Yun-teng LAO; Hai-yan YU; Yong LIU


    The vehicle routing problem (VRP) is a well-known combinatorial optimization issue in transportation and logistics network systems. There exist several limitations associated with the traditional VRP. Releasing the restricted conditions of traditional VRP has become a research focus in the past few decades. The vehicle routing problem with split deliveries and pickups (VRPSPDP) is particularly proposed to release the constraints on the visiting times per customer and vehicle capacity, that is, to allow the deliveries and pickups for each customer to be simultaneously split more than once. Few studies have focused on the VRPSPDP problem. In this paper we propose a two-stage heuristic method integrating the initial heuristic algorithm and hybrid heuristic algorithm to study the VRPSPDP problem. To validate the proposed algorithm, Solomon benchmark datasets and extended Solomon benchmark datasets were modified to compare with three other popular algorithms. A total of 18 datasets were used to evaluate the effectiveness of the proposed method. The computational results indicated that the proposed algorithm is superior to these three algorithms for VRPSPDP in terms of total travel cost and average loading rate.

  12. 49 CFR 375.705 - If a shipment is transported on more than one vehicle, what charges may I collect at delivery? (United States)


    ... vehicle, what charges may I collect at delivery? 375.705 Section 375.705 Transportation Other Regulations...; CONSUMER PROTECTION REGULATIONS Delivery of Shipments § 375.705 If a shipment is transported on more than one vehicle, what charges may I collect at delivery? (a) At your discretion, you may do one of...

  13. Penerapan Algoritma Differential Evolution untuk Penyelesaian Permasalahan Vehicle Routing Problem with Delivery and Pick-up

    Directory of Open Access Journals (Sweden)

    Ika Ayu Fajarwati


    Full Text Available Vehicle Routing Problem (VRP merupakan permasalahan optimasi kombinatorial kompleks yang memiliki peranan penting dalam manajemen sistem distribusi dengan tujuan meminimalkan biaya yang diperlukan, dimana penentuan biaya berkaitan dengan jarak dari rute yang ditempuh oleh armada distribusi. Ciri dari VRP yaitu penggunaan armada dengan kapasitas tertentu dan kegiatannya berpusat pada satu titik depot untuk melayani pelanggan pada titik-titik tertentu dengan jumlah permintaan yang diketahui. Kasus distribusi yang menggabungkan aktifitas pengiriman dan pengambilan produk termasuk dalam salah satu jenis VRP yaitu Vehicle Routing Problem Delivery and Pick-Up (VRP-DP. Banyak metode yang dapat digunakan untuk menyelesaikan permasalahan VRP-DP, salah satunya adalah metode optimasi metaheuristik yaitu Algoritma Differential Evolution yang akan diperkenalkan dalam penelitian ini. Hasil yang diharapkan nantinya adalah rute distribusi optimal untuk armada perusahaan sehingga menghasilkan jarak tempuh dan tentunya total biaya yang minimal dalam memenuhi semua permintaan pelanggan

  14. A novel nested liposome drug delivery vehicle capable of ultrasound triggered release of its payload. (United States)

    Ibsen, Stuart; Benchimol, Michael; Simberg, Dmitri; Schutt, Carolyn; Steiner, Jason; Esener, Sadik


    The use of focused ultrasound can be an effective method to locally highlight tumor tissue and specifically trigger the activation of echogenic drug delivery vehicles in an effort to reduce systemic chemotherapy side effects. Here we demonstrate a unique ultrasound triggered vehicle design and fabrication method where the payload and a perfluorocarbon gas microbubble are both encapsulated within the internal aqueous space of a liposome. This nested lipid shell geometry both stabilized the microbubble and ensured it was spatially close enough to interact with the liposome membrane at all times. The internal microbubble was shown to fragment the outer liposome membrane upon exposure to ultrasound at intensities of 1-1.5MPa. The focused ultrasound allowed the release of the internal payload to localized regions within tissue phantoms. The vehicles showed high payload loading efficiency of 16%, stability in blood of several hours, and low level macrophage recognition in vitro. High speed fluorescent videos present the first optical images of such vehicles interacting with ultrasound. This ability to open the outer membrane in small regions of deep tissue could provide a second level of spatial and temporal control beyond biochemical targeting, making these particles promising for in vivo animal studies.

  15. Effects of Fuel Type and Fuel Delivery System on Pollutant Emissions of Pride and Samand Vehicles

    Directory of Open Access Journals (Sweden)

    Akbar Sarhadi


    Full Text Available This research was aimed to study the effect of the type of fuel delivery system (petrol, dedicated or bifuel, the type of consumed fuel (petrol or gas, the portion of consumed fuel and also the duration of dual-fuelling in producing carbon monoxide, carbon dioxide and unburned hydrocarbons from Pride and Samand. According to research objectives, data gathering from 2000 vehicles has been done by visiting Hafiz Vehicle Inspection Center every day for 2 months. The results of this survey indicated that although there is no significant difference between various fuel delivery systems in terms of producing the carbon monoxide, carbon dioxide and unburned hydrocarbons by Samand, considering the emission amount of carbon dioxide, the engine performance of Pride in bifuel and dedicated state in GTXI and 132 types is more unsatisfactory than that of petrol state by 0.3 and 0.4%, respectively. On the other hand, consuming natural gas increases the amount of carbon monoxide emission in dual- fuel Pride by 0.18% and decreases that in dual-fuel Samand by 1.2%, which signifies the better design of Samand in terms of fuel pumps, used kit type and other engine parts to use this alternative fuel compared to Pride. Since the portion of consumed fuel and also duration of dual-fuelling does not have a significant effect on the amount of output pollutants from the studied vehicles, it can be claimed that the output substances from the vehicle exhaust are more related to the vehicle’s condition than the fuel type.

  16. Single walled carbon nanotubes as drug delivery vehicles: targeting doxorubicin to tumors. (United States)

    Meng, Lingjie; Zhang, Xiaoke; Lu, Qinghua; Fei, Zhaofu; Dyson, Paul J


    Single walled carbon nanotubes (SWNTs) are emerging as promising delivery vehicles for cancer diagnostics and chemotherapies due to their unique properties, including, remarkable cell membrane penetrability, high drug-carrying capacities, pH-dependent therapeutic unloading, prolonged circulating times and intrinsic fluorescent, photothermal, photoacoustic and Raman properties. In this leading opinion paper, we systemically discuss and evaluate the relationship of the biological safety of SWNTs with their physicochemical properties such as their length, purity, agglomeration state, concentration and surface functionalization. Other relevant issues, including the cellular uptake mechanism, biodistribution and metabolism of SWNTs are also reviewed. The design and preparation of SWNT-based drug delivery systems (DDSs) and their pharmacokinetic, cancer targeting and therapeutic properties both in vitro and in vivo are highlighted. Future opportunities and challenges of SWNT-based DDSs are also discussed.

  17. Interaction between drug delivery vehicles and cells under the effect of shear stress

    DEFF Research Database (Denmark)

    Godoy-Gallardo, Maria; Ek, Pramod Kumar; Jansman, M. M. T.


    Over the last decades, researchers have developed an ever greater and more ingenious variety of drug delivery vehicles (DDVs). This has made it possible to encapsulate a wide selection of therapeutic agents, ranging from proteins, enzymes, and peptides to hydrophilic and hydrophobic small drugs...... while, at the same time, allowing for drug release to be triggered through a diverse range of physical and chemical cues. While these advances are impressive, the field has been lacking behind in translating these systems into the clinic, mainly due to low predictability of in vitro and rodent in vivo...... are summarized. By grouping the discussion in three prominent classes of DDVs (lipidic and polymeric particles as well as inorganic nanoparticles), we hope to guide researchers within drug delivery into this exciting field and advance a further implementation of these assay systems within the development of DDVs....

  18. Towards Defined DNA and RNA Delivery Vehicles Using Nucleic Acid Nanotechnology

    DEFF Research Database (Denmark)

    Okholm, Anders Hauge; Schaffert, David Henning; Kjems, Jørgen


    an increasing interest to engineer-defined DNA and RNA vehicles for drug delivery. However, before this can be realized, key challenges must be overcome including structure integrity, efficient cell targeting, and drug release. The tunable nature of DNA and RNA assemblies allows for thorough investigations......Both DNA and RNA nanostructures show exceptional programmability, modularity, and self-assembly ability. Using DNA or RNA molecules it is possible to assemble monodisperse particles that are homogeneous in size and shape and with identical positioning of surface modifications. For therapeutic...... applications such nanoparticles are of particular interest as they can be tailored to target cells and reduce unwanted side effects due to particle heterogeneity. Recently, DNA and RNA nanostructures have demonstrated this potential by delivery of drugs to specific cells in vitro and in vivo. This has launched...

  19. Synthetic Nano-Low Density Lipoprotein as Targeted Drug DeliveryVehicle for Glioblastoma Multiforme

    Energy Technology Data Exchange (ETDEWEB)

    Nikanjam, Mina; Blakely, Eleanor A.; Bjornstad, Kathleen A.; Shu,Xiao; Budinger, Thomas F.; Forte, Trudy M.


    This paper discribes a synthetic low density lipoprotein(LDL) made by complexing a 29 amino acid that consists of a lipid bindingdomain and the LDL receptor binding domain with a lipid microemulsion.The nano-LDL particles were intermdiate in size between LDL and HDL andbound to LDL receptors on GBM brain tumor cells. Synthetic nano-LDLuptake by GBM cells was LDL receptor specific and dependent on cellreceptor number. It is suggested that these synthetic particles can serveas a delivery vehicle for hydophobic anti-tumor drugs by targeting theLDL receptor.

  20. A comprehensive overview of exosomes as drug delivery vehicles - endogenous nanocarriers for targeted cancer therapy. (United States)

    Johnsen, Kasper Bendix; Gudbergsson, Johann Mar; Skov, Martin Najbjerg; Pilgaard, Linda; Moos, Torben; Duroux, Meg


    Exosomes denote a class of secreted nanoparticles defined by size, surface protein and lipid composition, and the ability to carry RNA and proteins. They are important mediators of intercellular communication and regulators of the cellular niche, and their altered characteristics in many diseases, such as cancer, suggest them to be important both for diagnostic and therapeutic purposes, prompting the idea of using exosomes as drug delivery vehicles, especially for gene therapy. This review covers the current status of evidence presented in the field of exosome-based drug delivery systems. Components for successful exosome-based drug delivery, such as choice of donor cell, therapeutic cargo, use of targeting peptide, loading method and administration route are highlighted and discussed with a general focus pertaining to the results obtained in models of different cancer types. In addition, completed and on-going clinical trials are described, evaluating exosome-based therapies for the treatment of different cancer types. Due to their endogenous origin, exosome-based drug delivery systems may have advantages in the treatment of cancer, but their design needs further refinement to justify their usage on the clinical scale.

  1. Nano-Delivery Vehicles/Adjuvants for DNA Vaccination Against HIV. (United States)

    Dong, Yaqiong; Yang, Jun; Zhang, Jinchao; Zhang, Xin


    More than 75 million people has been infected HIV and it is responsible for nearly 36 million deaths on a global scale. As one of the deadliest infectious diseases, HIV is becoming the urgent issue of the global epidemic to tackle. In order to settle this problem from the source, some effective prevention strategies should be developed to control the pandemic of HIV. Vaccines, especially DNA vaccines, could be the optimal way to control the spread of HIV due to the unparalleled superiority that DNA vaccines could generate long-term humoral and cellular immune responses which could provide protective immunity for HIV. But the naked DNA could hardly enter into cells and is easily degraded by DNases and lysosomes, so designing effective delivery system is a promising strategy. Since delivery system could be constructed to promote efficient delivery of DNA into mammalian cells, protect them from degradation, and also could be established to be a target system to arrive at certain position of expectation. The current review discusses the potential of various nano-delivery vehicles/adjuvants such as polymer, lipid, liposome, peptide and inorganic material in improving efficiency of diverse modalities available for HIV DNA vaccines.

  2. Boswellia gum resin/chitosan polymer composites: Controlled delivery vehicles for aceclofenac. (United States)

    Jana, Sougata; Laha, Bibek; Maiti, Sabyasachi


    This study was undertaken to evaluate the effect of Boswellia gum resin on the properties of glutaraldehyde (GA) crosslinked chitosan polymer composites and their potential as oral delivery vehicles for a non-steroidal anti-inflammatory drug, aceclofenac. The incorporation of resinous material caused a significant improvement in drug entrapment efficiency (∼40%) of the polymer composites. Fourier transform infrared (FTIR) spectroscopic analysis confirmed the formation of chitosan-gum resin composites and did not show any evidence of drug-polymer chemical interaction. Field emission scanning electron microscopy (FE-SEM) suggested the formation of particulate polymer composites up to chitosan:gum resin mass ratio of 1:3. Only 8-17% drug was released into HCl solution (pH 1.2) in 2h. The drug release rate of polymer composites was faster in phosphate buffer solution (pH 6.8). The composites released ∼60-68% drug load in 7h. In same duration, the drug release rate suddenly boosted up to 92% as the concentration of gum resin in the composites was raised to 80%. The drug release mechanism deviated from non-Fickian to case-II type with increasing resin concentration in the composites. Hence, GA-treated Boswellia resin-chitosan composites could be considered as alternative vehicles for oral delivery of aceclofenac.

  3. The ex vivo neurotoxic, myotoxic and cardiotoxic activity of cucurbituril-based macrocyclic drug delivery vehicles. (United States)

    Oun, Rabbab; Floriano, Rafael S; Isaacs, Lyle; Rowan, Edward G; Wheate, Nial J


    The cucurbituril family of drug delivery vehicles have been examined for their tissue specific toxicity using ex vivo models. Cucurbit[6]uril (CB[6]), cucurbit[7]uril (CB[7]) and the linear cucurbituril-derivative Motor2 were examined for their neuro-, myo- and cardiotoxic activity and compared with β-cyclodextrin. The protective effect of drug encapsulation by CB[7] was also examined on the platinum-based anticancer drug cisplatin. The results show that none of the cucurbiturils have statistically measurable neurotoxicity as measured using mouse sciatic nerve compound action potential. Cucurbituril myotoxicity was measured by nerve-muscle force of contraction through chemical and electrical stimulation. Motor2 was found to display no myotoxicity, whereas both CB[6] and CB[7] showed myotoxic activity via a presynaptic effect. Finally, cardiotoxicity, which was measured by changes in the rate and force of right and left atria contraction, was observed for all three cucurbiturils. Free cisplatin displays neuro-, myo- and cardiotoxic activity, consistent with the side-effects seen in the clinic. Whilst CB[7] had no effect on the level of cisplatin's neurotoxic activity, drug encapsulation within the macrocycle had a marked reduction in both the drug's myo- and cardiotoxic activity. Overall the results are consistent with the relative lack of toxicity displayed by these macrocycles in whole animal acute systemic toxicity studies and indicate continued potential of cucurbiturils as drug delivery vehicles for the reduction of the side effects associated with platinum-based chemotherapy.


    Institute of Scientific and Technical Information of China (English)

    WANG Enrong; YING Liang; WANG Wanjun; RAKHEJA Subhash; SU Chunyi


    A hardware-in-the-loop (HIL) test and simulation platform is developed in the laboratory, so as to validate the performance characteristics of the proposed skyhook-based asymmetric semi-active controller in Part I, and examine the validity of the proposed MR-damper model in a system surrounding. A real-time monitor is designed to assess and monitor the responses of the quarter-vehicle model in the HIL platform, and to select the excitation, controller synthesis, and the output displays. A drive current circuit hardware employing PID feedback technique is developed to compensate for the time delays from the servo-controller and drive current circuit, in which a small resistance is integrated in the current amplifier circuit to provide the feedback signal. The experiments were performed to measure the responses of the quarter-vehicle MR-suspension models with fixed current and the proposed semi-active MR-damping variations, under harmonic, rounded pulse and random road excitations. The measured data were compared with the corresponding model results to examine the model and controller validity, and revealed generally good agreements in the model and tested results and very little sensitivity of the tested responses to variations in the sprung mass. The HIL test results validate the effectiveness of the proposed skyhook-based semi-active asymmetric controller and its high robustness against the vehicle load variations in view of the intelligent vehicle suspension design.

  5. Macrophages in gene therapy: cellular delivery vehicles and in vivo targets. (United States)

    Burke, B; Sumner, S; Maitland, N; Lewis, C E


    The appearance and activation of macrophages are thought to be rapid events in the development of many pathological lesions, including malignant tumors, atherosclerotic plaques, and arthritic joints. This has prompted recent attempts to use macrophages as novel cellular vehicles for gene therapy, in which macrophages are genetically modified ex vivo and then reintroduced into the body with the hope that a proportion will then home to the diseased site. Here, we critically review the efficacy of various gene transfer methods (viral, bacterial, protozoan, and various chemical and physical methods) in transfecting macrophages in vitro, and the results obtained when transfected macrophages are used as gene delivery vehicles. Finally, we discuss the use of various viral and nonviral methods to transfer genes to macrophages in vivo. As will be seen, definitive evidence for the use of macrophages as gene transfer vehicles has yet to be provided and awaits detailed trafficking studies in vivo. Moreover, although methods for transfecting macrophages have improved considerably in efficiency in recent years, targeting of gene transfer specifically to macrophages in vivo remains a problem. However, possible solutions to this include placing transgenes under the control of macrophage-specific promoters to limit expression to macrophages or stably transfecting CD34(+) precursors of monocytes/macrophages and then differentiating these cells into monocytes/macrophages ex vivo. The latter approach could conceivably lead to the bone marrow precursor cells of patients with inherited genetic disorders being permanently fortified or even replaced with genetically modified cells.

  6. Bacteriophages as vehicles for gene delivery into mammalian cells: prospects and problems. (United States)

    Bakhshinejad, Babak; Sadeghizadeh, Majid


    The identification of more efficient gene delivery vehicles (GDVs) is essential to fulfill the expectations of clinical gene therapy. Bacteriophages, due to their excellent safety profile, extreme stability under a variety of harsh environmental conditions and the capability for being genetically manipulated, have drawn a flurry of interest to be applied as a newly arisen category of gene delivery platforms. The incessant evolutionary interaction of bacteriophages with human cells has turned them into a part of our body's natural ecosystem. However, these carriers represent several barriers to gene transduction of mammalian cells. The lack of evolvement of specialized machinery for targeted cellular internalization, endosomal, lysosomal and proteasomal escape, cytoplasmic entry, nuclear localization and intranuclear transcription poses major challenges to the expression of the phage-carried gene. In this review, we describe pros and cons of bacteriophages as GDVs, provide an insight into numerous barriers that bacteriophages face for entry into and subsequent trafficking inside mammalian cells and elaborate on the strategies used to bypass these barriers. Tremendous genetic flexibility of bacteriophages to undergo numerous surface modifications through phage display technology has proven to be a turning point in the uncompromising efforts to surmount the limitations of phage-mediated gene expression. The revelatory outcomes of the studies undertaken within the recent years have been promising for phage-mediated gene delivery to move from concept to reality.

  7. Pectin matrix as oral drug delivery vehicle for colon cancer treatment. (United States)

    Wong, Tin Wui; Colombo, Gaia; Sonvico, Fabio


    Colon cancer is the fourth most common cancer globally with 639,000 deaths reported annually. Typical chemotherapy is provided by injection route to reduce tumor growth and metastasis. Recent research investigates the oral delivery profiles of chemotherapeutic agents. In comparison to injection, oral administration of drugs in the form of a colon-specific delivery system is expected to increase drug bioavailability at target site, reduce drug dose and systemic adverse effects. Pectin is suitable for use as colon-specific drug delivery vehicle as it is selectively digested by colonic microflora to release drug with minimal degradation in upper gastrointestinal tract. The present review examines the physicochemical attributes of formulation needed to retard drug release of pectin matrix prior to its arrival at colon, and evaluate the therapeutic value of pectin matrix in association with colon cancer. The review suggests that multi-particulate calcium pectinate matrix is an ideal carrier to orally deliver drugs for site-specific treatment of colon cancer as (1) crosslinking of pectin by calcium ions in a matrix negates drug release in upper gastrointestinal tract, (2) multi-particulate carrier has a slower transit and a higher contact time for drug action in colon than single-unit dosage form, and (3) both pectin and calcium have an indication to reduce the severity of colon cancer from the implication of diet and molecular biology studies. Pectin matrix demonstrates dual advantages as drug carrier and therapeutic for use in treatment of colon cancer.

  8. Soy lipophilic protein nanoparticles as a novel delivery vehicle for conjugated linoleic acid. (United States)

    Gao, Zhi-Ming; Zhu, Le-Ping; Yang, Xiao-Quan; He, Xiu-Ting; Wang, Jin-Mei; Guo, Jian; Qi, Jun-Ru; Wang, Li-Juan; Yin, Shou-Wei


    Soy lipophilic protein nanoparticles (LPP), which present a novel delivery vehicle for conjugated linoleic acid (CLA), were fabricated by ultrasonication of the soy lipophilic protein (LP), which exhibits unique characteristics including a high loading capacity, oxidation protection and a sustained releasing profile in vitro for CLA. The CLA-loaded LPP exhibited a mean diameter of 170 ± 0.63 nm and a loading capacity of 26.3 ± 0.40% (w/w). A coating of sodium caseinate (SC) on the surface improved the colloidal stability of the CLA-loaded LPP. This encapsulation conferred protection against the oxidation of CLA, by which the head space-oxygen consumption and hydrogen peroxide value were obviously decreased in comparison with the SC-encapsulated CLA and CLA alone. The delivery system enables a sustained releasing profile of CLA in a simulated gastrointestinal tract (GIT). These findings illustrate that the LPP could act as an effective delivery device for CLA, which could provide oxidation stability and a sustained release property.

  9. Molecular dynamics study on DNA nanotubes as drug delivery vehicle for anticancer drugs. (United States)

    Liang, Lijun; Shen, Jia-Wei; Wang, Qi


    In recent years, self-assembled DNA nanotubes have emerged as a type of nano-biomaterials with great potential for biomedical applications. To develop universal nanocarriers for smart and targeted drug delivery from DNA nanotubes, the understanding of interaction mechanism between DNA nanotubes and drugs is essential. In this study, the interactions between anti-cancer drugs and DNA nanotubes were investigated via molecular dynamics simulation. Our simulation results demonstrated that the DNA nanotubes could serve as a good drug delivery material by absorption of anti-cancer drugs with π-π interactions. At high concentration of anti-cancer drugs, most of the drugs could be absorbed by DNA nanotubes. Therefore, it could greatly decrease the aggregation of anti-cancer drugs in aqueous solution. In addition, the stability of DNA nanotubes could be improved with the absorption of anti-cancer drugs. These findings greatly enhance the understanding of the interaction mechanism of DNA nanotubes and anti-cancer drugs. Our study suggests that DNA nanotubes are promising delivery vehicles by strong absorption of anti-cancer drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Cascade Storage and Delivery System for a Multi Mission Space Exploration Vehicle (MMSEV) (United States)

    Yagoda, Evan; Swickrath, Michael; Stambaugh, Imelda


    NASA is developing a Multi Mission Space Exploration Vehicle (MMSEV) for missions beyond Low Earth Orbit (LEO). The MMSEV is a pressurized vehicle used to extend the human exploration envelope for Lunar, Near Earth Object (NEO), and Deep Space missions. The Johnson Space Center is developing the Environmental Control and Life Support System (ECLSS) for the MMSEV. The MMSEV s intended use is to support longer sortie lengths with multiple Extra Vehicular Activities (EVAs) on a higher magnitude than any previous vehicle. This paper presents an analysis of a high pressure oxygen cascade storage and delivery system that will accommodate the crew during long duration Intra Vehicular Activity (IVA) and capable of multiple high pressure oxygen fills to the Portable Life Support System (PLSS) worn by the crew during EVAs. A cascade is a high pressure gas cylinder system used for the refilling of smaller compressed gas cylinders. Each of the large cylinders are filled by a compressor, but the cascade system allows small cylinders to be filled without the need of a compressor. In addition, the cascade system is useful as a "reservoir" to accommodate low pressure needs. A regression model was developed to provide the mechanism to size the cascade systems subject to constraints such as number of crew, extravehicular activity duration and frequency, and ullage gas requirements under contingency scenarios. The sizing routine employed a numerical integration scheme to determine gas compressibility changes during depressurization and compressibility effects were captured using the Soave-Redlich-Kwong (SRK) equation of state. A multi-dimensional nonlinear optimization routine was used to find the minimum cascade tank system mass that meets the mission requirements. The sizing algorithms developed in this analysis provide a powerful framework to assess cascade filling, compressor, and hybrid systems to design long duration vehicle ECLSS architecture. 1

  11. Nutritionally enhanced fermented sausages as a vehicle for potential probiotic lactobacilli delivery. (United States)

    Rubio, Raquel; Jofré, Anna; Aymerich, Teresa; Guàrdia, Maria Dolors; Garriga, Margarita


    The suitability of three potential probiotic lactobacilli strains (Lactobacillus casei CTC1677, L. casei CTC1678 and Lactobacillus rhamnosus CTC1679), previously isolated from infants' faeces and characterized, and three commercial probiotic strains (Lactobacillus plantarum 299v, L. rhamnosus GG and L. casei Shirota) was assessed during the manufacture of low-acid fermented sausages (fuets) with reduced Na(+) and fat content. The inoculated strains were successfully monitored by RAPD-PCR during the process. L. rhamnosus CTC1679 was the only strain able to grow and dominate (levels ca. 10(8)CFU/g) the endogenous lactic acid bacteria population in two independent trials, throughout the ripening process. Thus, fuet containing L. rhamnosus CTC1679 as a starter culture could be a suitable vehicle for putative probiotic bacteria delivery. All the final products recorded a satisfactory overall sensory quality without any noticeable off-flavour, and with the characteristic sensory properties of low-acid fermented sausages.

  12. Multiobjective Vehicle Routing Problems With Simultaneous Delivery and Pickup and Time Windows: Formulation, Instances, and Algorithms. (United States)

    Wang, Jiahai; Zhou, Ying; Wang, Yong; Zhang, Jun; Chen, C L Philip; Zheng, Zibin


    This paper investigates a practical variant of the vehicle routing problem (VRP), called VRP with simultaneous delivery and pickup and time windows (VRPSDPTW), in the logistics industry. VRPSDPTW is an important logistics problem in closed-loop supply chain network optimization. VRPSDPTW exhibits multiobjective properties in real-world applications. In this paper, a general multiobjective VRPSDPTW (MO-VRPSDPTW) with five objectives is first defined, and then a set of MO-VRPSDPTW instances based on data from the real-world are introduced. These instances represent more realistic multiobjective nature and more challenging MO-VRPSDPTW cases. Finally, two algorithms, multiobjective local search (MOLS) and multiobjective memetic algorithm (MOMA), are designed, implemented and compared for solving MO-VRPSDPTW. The simulation results on the proposed real-world instances and traditional instances show that MOLS outperforms MOMA in most of instances. However, the superiority of MOLS over MOMA in real-world instances is not so obvious as in traditional instances.

  13. Albumin–Polymer–Drug Conjugates: Long Circulating, High Payload Drug Delivery Vehicles

    DEFF Research Database (Denmark)

    Smith, Anton Allen Abbotsford; Zuwala, Kaja; Pilgrim, Oliver;


    a marginal increase in the circulation lifetime of the drugs. We combine the benefits of the two platforms and at the same time overcome their respective limitations. Specifically, we develop the synthesis of albumin–polymer–drug conjugates to obtain long circulating, high payload drug delivery vehicles....... In vivo data validate that albumin endows the conjugate with a blood residence time similar to that of the protein and well exceeding that of the polymer. Therapeutic activity of the conjugates is validated using prodrugs of panobinostat, an HIV latency reversal agent, in which case the conjugates matched......Albumin is an exquisite tool of nature used in biomedicine to achieve long blood residence time for drugs, but the payload it can carry is typically limited to one molecule per protein. In contrast, synthetic macromolecular prodrugs contain multiple copies of drugs per polymer chain but offer only...

  14. DNA-carbon dots function as fluorescent vehicles for drug delivery. (United States)

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


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

  15. Food-Grade Organisms as Vaccine Biofactories and Oral Delivery Vehicles. (United States)

    Rosales-Mendoza, Sergio; Angulo, Carlos; Meza, Beatriz


    The use of food-grade organisms as recombinant vaccine expression hosts and delivery vehicles has been explored during the past 25 years, opening new avenues for vaccinology. Considering that oral immunization is a beneficial approach in terms of costs, patient comfort, and protection of mucosal tissues, the use of food-grade organisms can lead to highly advantageous vaccines in terms of costs, easy administration, and safety. The organisms currently used for this purpose are bacteria (Lactobacillus and Bacillus), yeasts, algae, plants, and insect species. Herein, a comparative and updated scenario on the production of oral vaccines in food-grade organisms is provided and placed in perspective. The status of clinical evaluations and the adoption of this technology by the industry are highlighted.

  16. DNA Nanostructures as Smart Drug-Delivery Vehicles and Molecular Devices. (United States)

    Linko, Veikko; Ora, Ari; Kostiainen, Mauri A


    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.

  17. Albumin–Polymer–Drug Conjugates: Long Circulating, High Payload Drug Delivery Vehicles

    DEFF Research Database (Denmark)

    Smith, Anton Allen Abbotsford; Zuwala, Kaja; Pilgram, Oliver


    Albumin is an exquisite tool of nature used in biomedicine to achieve long blood residence time for drugs, but the payload it can carry is typically limited to one molecule per protein. In contrast, synthetic macromolecular prodrugs contain multiple copies of drugs per polymer chain but offer only...... a marginal increase in the circulation lifetime of the drugs. We combine the benefits of the two platforms and at the same time overcome their respective limitations. Specifically, we develop the synthesis of albumin–polymer–drug conjugates to obtain long circulating, high payload drug delivery vehicles....... In vivo data validate that albumin endows the conjugate with a blood residence time similar to that of the protein and well exceeding that of the polymer. Therapeutic activity of the conjugates is validated using prodrugs of panobinostat, an HIV latency reversal agent, in which case the conjugates matched...

  18. Preparation and characterization of vinculin-targeted polymer–lipid nanoparticle as intracellular delivery vehicle

    Directory of Open Access Journals (Sweden)

    Wang J


    Full Text Available Junping Wang,* Ceren Örnek-Ballanco,* Jiahua Xu, Weiguo Yang, Xiaojun YuDepartment of Chemistry, Chemical Biology, and Biomedical Engineering, Stevens Institute of Technology, Hoboken, NJ, USA*These authors contributed equally to this workAbstract: Intracellular delivery vehicles have been extensively investigated as these can serve as an effective tool in studying the cellular mechanism, by delivering functional protein to specific locations of the cells. In the current study, a polymer–lipid nanoparticle (PLN system was developed as an intracellular delivery vehicle specifically targeting vinculin, a focal adhesion protein associated with cellular adhesive structures, such as focal adhesions and adherens junctions. The PLNs possessed an average size of 106 nm and had a positively charged surface. With a lower encapsulation efficiency 32% compared with poly(lactic-co-glycolic acid (PLGA nanoparticles (46%, the PLNs showed the sustained release profile of model drug BSA, while PLGA nanoparticles demonstrated an initial burst-release property. Cell-uptake experiments using mouse embryonic fibroblasts cultured in fibrin–fibronectin gels observed, under confocal microscope, that the anti-vinculin conjugated PLNs could successfully ship the cargo to the cytoplasm of fibroblasts, adhered to fibronectin–fibrin. With the use of cationic lipid, the unconjugated PLNs were shown to have high gene transfection efficiency. Furthermore, the unconjugated PLNs had nuclear-targeting capability in the absence of nuclear-localization signals. Therefore, the PLNs could be manipulated easily via different type of targeting ligands and could potentially be used as a powerful tool for cellular mechanism study, by delivering drugs to specific cellular organelles.Keywords: 3D gel, PLGA, targeting

  19. Preparation and evaluation of a contact lens vehicle for puerarin delivery. (United States)

    Xu, Jinku; Li, Xinsong; Sun, Fuqian


    The purpose of this study is to develop a soft contact lens vehicle for puerarin delivery to alleviate glaucoma. Poly(2-hydroxy-ethyl methacrylate-co-N-vinylpyrrolidone-co-methyl acrylate) (pHEMA-NVP-MA) contact lenses were prepared by UV irradiation of HEMA, NVP and MA, to which the cross-linker, a mixture of trimethylolpropane trimethacrylate (TMPTMA) and allyl methacrylate (AMA) (1:1, w/w) was added previously. The contact lenses were characterized by equilibrium swelling ratio (ESR) and tensile tester. The results showed that incorporation of poly-N-vinylpyrrolidone (PVP) component in the hydrogels caused increase of ESR and decrease of tensile strength. Co-polymerization of MA monomer in the hydrogel led to a slight drop of ESR and improved tensile strength of hydrogel. Four kinds of hydrated contact lenses with different PVP content were presoaked in PBS solution of puerarin and the in vitro drug release was measured. The contact lenses matrix incorporated with PVP had a remarkable loading capacity of puerarin. In rabbit eyes, the presoaked contact lenses extended the mean resident time of puerarin to 77.45 min from 12.88 min of 1% puerarin eye drops. Moreover, contact lens presoaked in puerarin solution at the concentration of 0.802 mg/ml showed about the same bioavailability (AUC(0-t)) in tear fluid as that of the puerarin eye drops. This kind of presoaked contact lens has potential application as vehicle of puerarin to alleviate glaucoma.

  20. In vivo biocompatibility, clearance, and biodistribution of albumin vehicles for pulmonary drug delivery. (United States)

    Woods, A; Patel, A; Spina, D; Riffo-Vasquez, Y; Babin-Morgan, A; de Rosales, R T M; Sunassee, K; Clark, S; Collins, H; Bruce, K; Dailey, L A; Forbes, B


    The development of clinically acceptable albumin-based nanoparticle formulations for use in pulmonary drug delivery has been hindered by concerns about the toxicity of nanomaterials in the lungs combined with a lack of information on albumin nanoparticle clearance kinetics and biodistribution. In this study, the in vivo biocompatibility of albumin nanoparticles was investigated following a single administration of 2, 20, and 390μg/mouse, showing no inflammatory response (TNF-α and IL-6, cellular infiltration and protein concentration) compared to vehicle controls at the two lower doses, but elevated mononucleocytes and a mild inflammatory effect at the highest dose tested. The biodistribution and clearance of (111)In labelled albumin solution and nanoparticles over 48h following a single pulmonary administration to mice was investigated by single photon emission computed tomography and X-ray computed tomography imaging and terminal biodistribution studies. (111)In labelled albumin nanoparticles were cleared more slowly from the mouse lung than (111)In albumin solution (64.1±8.5% vs 40.6±3.3% at t=48h, respectively), with significantly higher (P24h indicating that small amounts of activity were cleared from the lungs both by translocation across the lung mucosal barrier, as well as mucociliary clearance. This study provides important information on the fate of albumin vehicles in the lungs, which may be used to direct future formulation design of inhaled nanomedicines.

  1. Construction of a Nanodiamond–Tamoxifen Complex as a Breast Cancer Drug Delivery Vehicle

    Directory of Open Access Journals (Sweden)

    Linda-Lucila Landeros-Martínez


    Full Text Available According to the World Health Organization, breast cancer represents 16% of all cancer cases in women and is the second most common cancer. In the past decades, the mortality among patients with metastasis breast cancer has been reduced significantly via drug delivery by means of nanodiamond therapies, which are both biocompatible and scalable. In this study, we determined a theoretical pathway for the construction of a nanodiamond–tamoxifen complex that will act as a drug delivery vehicle for targeting tumor tissues of breast cancer. The tamoxifen pharmacophore was defined and the binding zone was identified for the electrostatic interaction between tamoxifen and a functionalized site of a nanodiamond particle allowing for attachment of the payload (this drug to the surface of the nanodiamond particle. In addition, an analysis of the intermolecular interaction between the nanodiamond and tamoxifen was conducted, showing three hydrogen bonds complying fully with Lipinski’s rule of five, which states that a compound should have five or fewer hydrogen bonds to be permeating and easily absorbed by the body (qualitative prediction. All calculations were performed using the conceptual Density Functional Theory with the M06 functional and the basis set 6-31G(d. The solvent effect has been taken into account by an implicit model, the conductor like polarizable continuum model.

  2. Bolaamphiphilic vesicles encapsulating iron oxide nanoparticles: new vehicles for magnetically targeted drug delivery. (United States)

    Philosof-Mazor, Liron; Dakwar, George R; Popov, Mary; Kolusheva, Sofiya; Shames, Alexander; Linder, Charles; Greenberg, Sarina; Heldman, Eliahu; Stepensky, David; Jelinek, Raz


    Bolaamphiphiles - amphiphilic molecules consisting of two hydrophilic headgroups linked by a hydrophobic chain - form highly stable vesicles consisting of a monolayer membrane that can be used as vehicles to deliver drugs across biological membranes, particularly the blood-brain barrier (BBB). We prepared new vesicles comprising bolaamphiphiles (bolavesicles) that encapsulate iron oxide nanoparticles (IONPs) and investigated their suitability for targeted drug delivery. Bolavesicles displaying different headgroups were studied, and the effect of IONP encapsulation upon membrane interactions and cell uptake were examined. Experiments revealed more pronounced membrane interactions of the bolavesicles assembled with IONPs. Furthermore, enhanced internalization and stability of the IONP-bolavesicles were observed in b.End3 brain microvessel endothelial cells - an in vitro model of the blood-brain barrier. Our findings indicate that embedded IONPs modulate bolavesicles' physicochemical properties, endow higher vesicle stability, and enhance their membrane permeability and cellular uptake. IONP-bolavesicles thus constitute a promising drug delivery platform, potentially targeted to the desired location using external magnetic field. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. DNA Binding Proteins and Drug Delivery Vehicles: Tales of Elephants and Snakes. (United States)

    Karpel, Richard L


    We compare the DNA-interactive properties of bacteriophage T4 gene 32 protein (gp32) with those of crotamine, a component of the venom of the South American rattlesnake. Gene 32 protein is a classical single-stranded DNA binding protein that has served as a model for this class of proteins. We discuss its biological functions, structure, binding specificities, and how it controls its own expression. In addition, we delineate the roles of the structural domains of gp32 and how they regulate the protein's various activities. Crotamine, a component of the venom of the South American rattlesnake, is probably not a DNA binding protein in nature, but clearly shows significant DNA binding in vitro. Crotamine has been shown to selectively disrupt rapidly dividing cells and this specificity has been demonstrated for crotamine-facilitated delivery of plasmid DNA Thus, crotamine, or a variant of the protein, could have important clinical and/or diagnostic roles. Understanding its DNA binding properties may therefore lead to more effective drug delivery vehicles.

  4. Interaction between drug delivery vehicles and cells under the effect of shear stress. (United States)

    Godoy-Gallardo, M; Ek, P K; Jansman, M M T; Wohl, B M; Hosta-Rigau, L


    Over the last decades, researchers have developed an ever greater and more ingenious variety of drug delivery vehicles (DDVs). This has made it possible to encapsulate a wide selection of therapeutic agents, ranging from proteins, enzymes, and peptides to hydrophilic and hydrophobic small drugs while, at the same time, allowing for drug release to be triggered through a diverse range of physical and chemical cues. While these advances are impressive, the field has been lacking behind in translating these systems into the clinic, mainly due to low predictability of in vitro and rodent in vivo models. An important factor within the complex and dynamic human in vivo environment is the shear flow observed within our circulatory system and many other tissues. Within this review, recent advances to leverage microfluidic devices to better mimic these conditions through novel in vitro assays are summarized. By grouping the discussion in three prominent classes of DDVs (lipidic and polymeric particles as well as inorganic nanoparticles), we hope to guide researchers within drug delivery into this exciting field and advance a further implementation of these assay systems within the development of DDVs.

  5. Retention of in vitro and in vivo BMP-2 bioactivities in sustained delivery vehicles for bone tissue engineering

    NARCIS (Netherlands)

    Kempen, Diederik H. R.; Lu, Lichun; Hefferan, Teresa E.; Creemers, Laura B.; Maran, Avudaiappan; Classic, Kelly L.; Dhert, Wouter J. A.; Yaszemski, Michael J.


    In this study, we investigated the in vitro and in vivo biological activities of bone morphogenetic protein 2 (BMP-2) released from four sustained delivery vehicles for bone regeneration. BMP-2 was incorporated into (1) a gelatin hydrogel, (2) poly(lactic-co-glycolic acid) (PLGA) microspheres embedd

  6. Glutathione-responsive nano-vehicles as a promising platform for targeted intracellular drug and gene delivery

    NARCIS (Netherlands)

    Cheng, Ru; Feng, Fang; Meng, Fenghua; Deng, Chao; Feijen, Jan; Zhong, Zhiyuan


    The past couple of years have witnessed a tremendous progress in the development of glutathione-responsive nano-vehicles for targeted intracellular drug and gene delivery, as driven by the facts that (i) many therapeutics (e.g. anti-cancer drugs, photosensitizers, and anti-oxidants) and

  7. Retention of in vitro and in vivo BMP-2 bioactivities in sustained delivery vehicles for bone tissue engineering

    NARCIS (Netherlands)

    Kempen, Diederik H. R.; Lu, Lichun; Hefferan, Teresa E.; Creemers, Laura B.; Maran, Avudaiappan; Classic, Kelly L.; Dhert, Wouter J. A.; Yaszemski, Michael J.

    In this study, we investigated the in vitro and in vivo biological activities of bone morphogenetic protein 2 (BMP-2) released from four sustained delivery vehicles for bone regeneration. BMP-2 was incorporated into (1) a gelatin hydrogel, (2) poly(lactic-co-glycolic acid) (PLGA) microspheres

  8. Glutathione-responsive nano-vehicles as a promising platform for targeted intracellular drug and gene delivery

    NARCIS (Netherlands)

    Cheng, Ru; Feng, Fang; Meng, Fenghua; Deng, Chao; Feijen, Jan; Zhong, Zhiyuan


    The past couple of years have witnessed a tremendous progress in the development of glutathione-responsive nano-vehicles for targeted intracellular drug and gene delivery, as driven by the facts that (i) many therapeutics (e.g. anti-cancer drugs, photosensitizers, and anti-oxidants) and biotherapeut

  9. Metal based nanoparticles as cancer antigen delivery vehicles for macrophage based antitumor vaccine. (United States)

    Chattopadhyay, Sourav; Dash, Sandeep Kumar; Mandal, Debasis; Das, Balaram; Tripathy, Satyajit; Dey, Aditi; Pramanik, Panchanan; Roy, Somenath


    In the present study, we would like to evaluate the efficacy of modified metal oxide nanoparticles (NPs) as cancer antigen delivery vehicles for macrophage (MФs) based antitumor vaccine. The cobalt oxide nanoparticles (CoO NPs) were promising tools for delivery of antigens to antigen presenting cells and have induced an antitumor immune response. Synthesized CoO NPs were modified by N-phosphonomethyliminodiacetic acid (PMIDA), facilitated the conjugation of lysate antigen, i.e. cancer antigen derived from lysis of cancer cells. The cancer cell lysate antigen conjugated PMIDA-CoO NPs (Ag-PMIDA-CoO NPs) successfully activated macrophage (MФ) evident by the increasing the serum IFN-γ and TNF-α level. Immunization of mice with the Ag-PMIDA-CoO NPs constructed an efficient immunological adjuvant induced anticancer IgG responses, and increased the antibody dependent cellular cytotoxicity (ADCC) response than only lysate antigen treated group to combat the cancer cell. The nanocomplexes enhanced the anticancer CD4(+)T cell response in mice. The result showed that Ag-PMIDA-CoO NPs can stimulate the immune responses over only lysate antigens, which are the most important findings in this study. These NP-mediated Ag deliveries may significantly improve the anticancer immune response by activating MФs and may act as adjuvant and will balance the pro-inflammatory and anti-inflammatory immunoresponse. The crosstalk between the activated MФ with other immune competent cells will be monitored by measuring the cytokines which illustrate the total immunological network setups.

  10. Intramyocardial sustained delivery of placental growth factor using nanoparticles as a vehicle for delivery in the rat infarct model

    Directory of Open Access Journals (Sweden)

    Shum-Tim D


    sustained release of PlGF from the particles over a 120-hour period.Conclusion: The use of nanoparticles as a vehicle for PlGF delivery, as opposed to the direct injection of the growth factor after acute myocardial infarction, can provide sustained slow-release PlGF therapy, enhancing the positive effects of the growth factor in the setting of acute myocardial ischemia.Keywords: nanotechnology, serum cytokines, myocardial therapy, angiogenesis, regenerative medicine

  11. Chocolate rheology

    Directory of Open Access Journals (Sweden)

    Estela Vidal Gonçalves


    Full Text Available Rheology is the science that studies the deformation and flow of solids and fluids under the influence of mechanical forces. The rheological measures of a product in the stage of manufacture can be useful in quality control. The microstructure of a product can also be correlated with its rheological behavior allowing for the development of new materials. Rheometry permits attainment of rheological equations applied in process engineering, particularly unit operations that involve heat and mass transfer. Consumer demands make it possible to obtain a product that complies with these requirements. Chocolate industries work with products in a liquid phase in conching, tempering, and also during pumping operations. A good design of each type of equipment is essential for optimum processing. In the design of every process, it is necessary to know the physical characteristics of the product. The rheological behavior of chocolate can help to know the characteristics of application of the product and its consumers. Foods are generally in a metastable state. Their texture depends on the structural changes that occur during processing. Molten chocolate is a suspension with properties that are strongly affected by particle characteristics including not only the dispersed particles but also the fat crystals formed during chocolate cooling and solidification. Chocolate rheology is extensively studied, and it is known that chocolate texture and stability is strongly affected by the presence of specific crystals

  12. Synthesis of a drug delivery vehicle for cancer treatment utilizing DNA-functionalized gold nanoparticles (United States)

    Brann, Tyler

    The treatment of cancer with chemotherapeutic agents has made great strides in the last few decades but still introduces major systemic side effects. The potent drugs needed to kill cancer cells often cause irreparable damage to otherwise healthy organs leading to further morbidity and mortality. A therapy with intrinsic selective properties and/or an inducible activation has the potential to change the way cancer can be treated. Gold nanoparticles (GNPs) are biocompatible and chemically versatile tools that can be readily functionalized to serve as molecular vehicles. The ability of these particles to strongly absorb light with wavelengths in the therapeutic window combined with the heating effect of surface plasmon resonance makes them uniquely suited for noninvasive heating in biologic applications. Specially designed DNA aptamers have shown their ability to serve as drug carriers through intercalation as well as directly acting as therapeutic agents. By combining these separate molecules a multifaceted drug delivery vehicle can be created with great potential as a selective and controllable treatment for cancer. Oligonucleotide-coated GNPs have been created using spherical GNPs but little work has been reported using gold nanoplates in this way. Using the Diasynth method gold nanoplates were produced to absorb strongly in the therapeutic near infrared (nIR) window. These particles were functionalized with two DNA oligonucleotides: one serving as an intercalation site for doxorubicin, and another, AS1411, serving directly as an anticancer targeting/therapeutic agent. These functional particles were fully synthesized and processed along with confirmation of DNA functionalization and doxorubicin intercalation. Doxorubicin is released via denaturation of the DNA structure into which doxorubicin is intercalated upon the heating of the gold nanoplate well above the DNA melting temperature. This temperature increase, due to light stimulation of surface plasmon

  13. Cell mediated therapeutics for cancer treatment: Tumor homing cells as therapeutic delivery vehicles (United States)

    Balivada, Sivasai

    Many cell types were known to have migratory properties towards tumors and different research groups have shown reliable results regarding cells as delivery vehicles of therapeutics for targeted cancer treatment. Present report discusses proof of concept for 1. Cell mediated delivery of Magnetic nanoparticles (MNPs) and targeted Magnetic hyperthermia (MHT) as a cancer treatment by using in vivo mouse cancer models, 2. Cells surface engineering with chimeric proteins for targeted cancer treatment by using in vitro models. 1. Tumor homing cells can carry MNPs specifically to the tumor site and tumor burden will decrease after alternating magnetic field (AMF) exposure. To test this hypothesis, first we loaded Fe/Fe3O4 bi-magnetic NPs into neural progenitor cells (NPCs), which were previously shown to migrate towards melanoma tumors. We observed that NPCs loaded with MNPs travel to subcutaneous melanoma tumors. After alternating magnetic field (AMF) exposure, the targeted delivery of MNPs by the NPCs resulted in a mild decrease in tumor size (Chapter-2). Monocytes/macrophages (Mo/Ma) are known to infiltrate tumor sites, and also have phagocytic activity which can increase their uptake of MNPs. To test Mo/Ma-mediated MHT we transplanted Mo/Ma loaded with MNPs into a mouse model of pancreatic peritoneal carcinomatosis. We observed that MNP-loaded Mo/Ma infiltrated pancreatic tumors and, after AMF treatment, significantly prolonged the lives of mice bearing disseminated intraperitoneal pancreatic tumors (Chapter-3). 2. Targeted cancer treatment could be achieved by engineering tumor homing cell surfaces with tumor proteases cleavable, cancer cell specific recombinant therapeutic proteins. To test this, Urokinase and Calpain (tumor specific proteases) cleavable; prostate cancer cell (CaP) specific (CaP1 targeting peptide); apoptosis inducible (Caspase3 V266ED3)- rCasp3V266ED3 chimeric protein was designed in silico. Hypothesized membrane anchored chimeric protein (rCasp3V

  14. Vehicle Routing Problem with Time Windows and Simultaneous Delivery and Pick-Up Service Based on MCPSO

    Directory of Open Access Journals (Sweden)

    Xiaobing Gan


    Full Text Available This paper considers two additional factors of the widely researched vehicle routing problem with time windows (VRPTW. The two factors, which are very common characteristics in realworld, are uncertain number of vehicles and simultaneous delivery and pick-up service. Using minimization of the total transport costs as the objective of the extension VRPTW, a mathematic model is constructed. To solve the problem, an efficient multiswarm cooperative particle swarm optimization (MCPSO algorithm is applied. And a new encoding method is proposed for the extension VRPTW. Finally, comparing with genetic algorithm (GA and particle swarm optimization (PSO algorithm, the MCPSO algorithm performs best for solving this problem.

  15. Green synthesis of bacterial gold nanoparticles conjugated to resveratrol as delivery vehicles. (United States)

    Kumar, C Ganesh; Poornachandra, Y; Mamidyala, Suman Kumar


    Bio-directed synthesis of metal nanoparticles is gaining importance in view of their biocompatibility, low toxicity and eco-friendly characteristics. The present study describes the application of resveratrol conjugated gold nanoparticles as effective delivery vehicles. The green chemistry approach was used for the synthesis of gold nanoparticles by using the culture supernatant of Delftia sp. strain KCM-006. The synthesized gold nanoparticles were mono-dispersed, spherical in shape with an average size of 11.3 nm. They were found to be photoluminescent and crystalline in nature with a zeta potential of -25 mV, indicating their high stability. Resveratrol, an anticancer drug, was conjugated to these gold nanoparticles (RSV-AuNP). The cell viability and immunocytochemistry analysis with human lung cancer cell line (A549) demonstrated that RSV-AuNPs were 65% more effective as drug when compared to resveratrol alone. In vitro observations on the drug release from these nanoparticles exhibited pH dependency; the release was significant (95%) under acidic conditions (pH 5.2) when compared to physiological conditions (pH 7.4).

  16. Silk-hyaluronan-based composite hydrogels: a novel, securable vehicle for drug delivery. (United States)

    Elia, Roberto; Newhide, Danny R; Pedevillano, Paul D; Reiss, G Russell; Firpo, Matthew A; Hsu, Edward W; Kaplan, David L; Prestwich, Glenn D; Peattie, Robert A


    A new, biocompatible hyaluronic acid (HA)-silk hydrogel composite was fabricated and tested for use as a securable drug delivery vehicle. The composite consisted of a hydrogel formed by cross-linking thiol-modified HA with poly(ethylene glycol)-diacrylate, within which was embedded a reinforcing mat composed of electrospun silk fibroin protein. Both HA and silk are biocompatible, selectively degradable biomaterials with independently controllable material properties. Mechanical characterization showed the composite tensile strength as fabricated to be 4.43 ± 2.87 kPa, two orders of magnitude above estimated tensions found around potential target organs. In the presence of hyaluronidase (HAse) in vitro, the rate of gel degradation increased with enzyme concentration although the reinforcing silk mesh was not digested. Composite gels demonstrated the ability to store and sustainably deliver therapeutic agents. Time constants for in vitro release of selected representative antibacterial and anti-inflammatory drugs varied from 46.7 min for cortisone to 418 min for hydrocortisone. This biocomposite showed promising mechanical characteristics for direct fastening to tissue and organs, as well as controllable degradation properties suitable for storage and release of therapeutically relevant drugs.

  17. A ceramic drug delivery vehicle for oral administration of highly potent opioids. (United States)

    Forsgren, Johan; Jämstorp, Erik; Bredenberg, Susanne; Engqvist, Håkan; Strømme, Maria


    Pellets composed of the ceramic material Halloysite and microcrystalline cellulose were synthesized with the aim of producing a drug delivery vehicle for sustained release of the opioid Fentanyl with low risk for dose dumping at oral intake of the highly potent drug. Drug release profiles of intact and crushed pellets, to simulate swallowing without or with chewing, in pH 6.8, pH 1, and in 48% ethanol were recorded in order to replicate the conditions in the small intestines, in the stomach, as well as cointake of the drug with alcohol. The drug release was analyzed by employing the Weibull equation, which showed that the release profiles were either governed by fickian diffusion (intact pellets in pH 6.8 and in ethanol) or by diffusion in a fractal or disordered pore network (intact pellets in pH 1 and crushed pellets in all solutions). A sustained release for approximately 3-4 h was obtained in all studied solutions from intact pellets, whereas crushed pellets released the drug content during approximately 2-3 h. The finding that a sustained release profile could be obtained both in alcohol and after crushing of the pellets, shows that the ceramic carrier under investigation, at least to some extent, hampers dose dumping, and may thus be a promising material in future developments of new opioid containing oral dosage forms.

  18. Direct observation of key photoinduced dynamics in a potential nano-delivery vehicle of cancer drugs. (United States)

    Sardar, Samim; Chaudhuri, Siddhi; Kar, Prasenjit; Sarkar, Soumik; Lemmens, Peter; Pal, Samir Kumar


    In recent times, significant achievements in the use of zinc oxide (ZnO) nanoparticles (NPs) as delivery vehicles of cancer drugs have been made. The present study is an attempt to explore the key photoinduced dynamics in ZnO NPs upon complexation with a model cancer drug protoporphyrin IX (PP). The nanohybrid has been characterized by FTIR, Raman scattering and UV-Vis absorption spectroscopy. Picosecond-resolved Förster resonance energy transfer (FRET) from the defect mediated emission of ZnO NPs to PP has been used to study the formation of the nanohybrid at the molecular level. Picosecond-resolved fluorescence studies of PP-ZnO nanohybrids reveal efficient electron migration from photoexcited PP to ZnO, eventually enhancing the ROS activity. The dichlorofluorescin (DCFH) oxidation and no oxidation of luminol in PP/PP-ZnO nanohybrids upon green light illumination unravel that the nature of ROS is essentially singlet oxygen rather than superoxide anions. Surface mediated photocatalysis of methylene blue (MB) in an aqueous solution of the nanohybrid has also been investigated. Direct evidence of the role of electron transfer as a key player in enhanced ROS generation from the nanohybrid is also clear from the photocurrent measurement studies. We have also used the nanohybrid in a model photodynamic therapy application in a light sensitized bacteriological culture experiment.

  19. Targeting gallbladder carcinoma: bone marrow-derived stem cells as therapeutic delivery vehicles of myxoma virus

    Institute of Scientific and Technical Information of China (English)

    Weng Mingzhe; Zhang Mingdi; Qin Yiyu; Gong Wei; Tang Zhaohui; Quan Zhiwei; Wu Kejin


    Background Gallbladder carcinoma (GBC) has a high mortality rate,requiring synergistic anti-tumor management for effective treatment.The myxoma virus (MYXV) exhibits a modest clinical value through its oncolytic potential and narrow host tropism.Methods We performed viral replication assays,cell viability assays,migration assays,and xenograft tumor models to demonstrate that bone marrow-derived stem cells (BMSCs) may enhance efficiency of intravenous MYXV delivery.Results We examined the permissiveness of various GBC cell lines towards MYXV infection and found two supported single and multiple rounds of MYXV replication,leading to an oncolytic effect.Furthermore,we found that BMSCs exhibited tropism for GBC cells within a Matrigel migration system.BMSCs failed to affect the growth of GBC cells,in terms of tumor volume and survival time.Finally,we demonstrated in vivo that intravenous injection of MYXV-infected BMSCs significantly improves the oncolytic effect of MYXV alone,almost to the same extent as intratumoral injection of MYXV.Conclusion This study indicates that BMSCs are a promising novel vehicle for MYXV to clinically address gallbladder tumors.

  20. Chemically modified inulin microparticles serving dual function as a protein antigen delivery vehicle and immunostimulatory adjuvant. (United States)

    Gallovic, Matthew D; Montjoy, Douglas G; Collier, Michael A; Do, Clement; Wyslouzil, Barbara E; Bachelder, Eric M; Ainslie, Kristy M


    To develop a new subunit vaccine adjuvant, we chemically modified a naturally-occurring, immunostimulatory inulin polysaccharide to produce an acid-sensitive biopolymer (acetalated inulin, Ace-IN). Various hydrophobic Ace-IN polymers were formed into microparticles (MPs) by oil-in-water emulsions followed by solvent evaporation These Ace-IN MPs possessed tunable degradation characteristics that, unlike polyesters used in FDA-approved microparticulate formulations, had only pH-neutral hydrolytic byproducts. Macrophages were passively targeted with cytocompatible Ace-IN MPs. TNF-α production by macrophages treated with Ace-IN MPs could be altered by adjusting the polymers' chemistry. Mice immunized with Ace-IN MPs encapsulating a model ovalbumin (OVA) antigen showed higher production of anti-OVA IgG antibody levels relative to soluble antigen. The antibody titers were also comparable to an alum-based formulation. This proof-of-concept establishes the potential for chemically-modified inulin MPs to simultaneously enable dual functionality as a stimuli-controlled antigen delivery vehicle and immunostimulatory adjuvant.

  1. Cinnamate of inulin as a vehicle for delivery of colonic drugs. (United States)

    López-Molina, Dorotea; Chazarra, Soledad; How, Chee Wun; Pruidze, Nikolov; Navarro-Perán, Enma; García-Cánovas, Francisco; García-Ruiz, Pedro Antonio; Rojas-Melgarejo, Francisco; Rodríguez-López, José Neptuno


    Colon diseases are difficult to treat because oral administrated drugs are absorbed at the stomach and intestine levels and they do not reach colon; in addition, intravenous administrated drugs are eliminated from the body before reaching colon. Inulin is a naturally occurring polysaccharide found in many plants. It consists of β 2-1 linked D-fructose molecules having a glucosyl unit at the reducing end. Various inulin and dextran hydrogels have been developed that serve as potential carrier for introduction of drugs into the colon. Because inulin is not absorbed in the stomach or in the small intestine, and inulin is degraded by colonic bacteria, drugs encapsulated in inulin-coated vesicles could be specifically liberated in the colon. Therefore, the use of inulin-coated vesicles could represent an advance for the treatment of colon diseases. Here, we study the use of a cinnamoylated derivative of chicory inulin as a vehicle for the controlled delivery of colonic drugs. The encapsulation of methotrexate in inulin vesicles and its release and activity was studied in colon cancer cells in cultures.

  2. Collagen-GAG Scaffolds Grafted Onto Myocardial Infarcts in a Rat Model:A Delivery Vehicle for Mesenchymal Stem Cells

    Institute of Scientific and Technical Information of China (English)



    1 IntroductionThe objective of the present study was to investigate the response of rat myocardial scar tissue to type I collagen-glycosaminoglycan (GAG) tissue engineering scaffolds, and to assess the feasibility of using a collagen-GAG scaffold as a delivery vehicle for bone marrow-derived mesenchymal stem cells. The benefits of employing the collagen-GAG scaffold for this application include the following:(1) the large surface area of the three-dimensional sponge-like material allows for the delivery of ...

  3. In vitro analysis of the TAT protein transduction domain as a drug delivery vehicle in protozoan parasites. (United States)

    Chin Lee, Stephanie Hui; Jefferies, Ryan; Watt, Paul; Hopkins, Richard; Sotzik, Frank; Reid, Simon; Armson, Anthony; Boxell, Annika; Ryan, Una


    The present study was undertaken to analyse the capability of HIV-1 derived TAT protein transduction domain (PTD) fused with Green Fluorescent Protein (TAT-GFP) as a delivery vehicle into a range of protozoan parasites. Successful transduction of native purified TAT-GFP was observed by fluorescent microscopy in Cryptosporidium parvum, Giardia duodenalis, and Neospora caninum. The ability to transduce peptides and other cargo into protozoan parasites, will greatly assist in the delivery of future peptide-based drugs and target validation peptides.

  4. Production and delivery batch scheduling with a common due date and multiple vehicles to minimize total cost (United States)

    Prasetyaningsih, E.; Suprayogi; Samadhi, TMAA; Halim, AH


    This paper studies production and delivery batch scheduling problems for a single- supplier-to-a-single-manufacturer case, with multiple capacitated vehicles wherein different holding costs between in-process and completed parts are allowed. In the problem, the parts of a single item are first batched,then the resulting batches are processed on a single machine. All completed batches are transported in a number of deliveries in order to be received at a common due date. The objective is to find the integrated schedule of production and delivery batches so as to satisfy its due date and to minimize the total cost of associated in-process parts inventory, completed parts inventory and delivery. It should be noted that both holding costs constitute a derivation of the so-called actual flow time, and the delivery cost is proportional to the required number of deliveries. The problem can be formulated as an integer non-linier programming and it is solved optimally by Lingo 11.0 software. Numerical experiences show that there are two patterns of batch sizes affected by the ratio of holding costs of in-process and completed parts. It can be used by practitioners to solve the realistic integrated production and delivery batch scheduling problem.

  5. Exact Solutions to the Symmetric and Asymmetric Vehicle Routing Problem with Simultaneous Delivery and Pick-Up

    Directory of Open Access Journals (Sweden)

    Julia Rieck


    Full Text Available In reverse logistics networks, products (e.g., bottles or containers have to be transported from a depot to customer locations and, after use, from customer locations back to the depot. In order to operate economically beneficial, companies prefer a simultaneous delivery and pick-up service. The resulting Vehicle Routing Problem with Simultaneous Delivery and Pick-up (VRPSDP is an operational problem, which has to be solved daily by many companies. We present two mixed-integer linear model formulations for the VRPSDP, namely a vehicle-flow and a commodity-flow model. In order to strengthen the models, domain-reducing preprocessing techniques, and effective cutting planes are outlined. Symmetric benchmark instances known from the literature as well as new asymmetric instances derived from real-world problems are solved to optimality using CPLEX 12.1.

  6. Vehicle Route Replanning for Fruit and Vegetable Delivery%果蔬运输车辆路径再规划

    Institute of Scientific and Technical Information of China (English)

    黄华芳; 王以忠; 李达; 门建婷; 张平; 黄国全


    果蔬具有易腐性,在销售、消费时存在很强的时效性,这就要求合理规划果蔬运输车辆的配送路径.在果蔬配送途中,当某运输车遇到特殊情况无法按时送达配送点时,应当对其他运输车进行路径再规划.给出了带时间窗的果蔬运输车辆路径再规划的数学模型,并采用改进蚁群算法进行了求解.仿真试验结果表明,模型及算法可以有效地优化果蔬配送新路线,为降低果蔬腐烂损失、提高销售收入、有效控制运作成本提供了理论支持.%Since fruit and vegetable are highly perishable, and have strong timeliness in selling and consuming, the delivery routes of transport vehicles must be planned reasonably. On the path of fruit and vegetable delivery, a transport vehicle may encounter some unusual circumstances and may not arrive at the next distribution site in time. In this case, the vehicle routes of other transport vehicles should be replanned. A mathematical model for vehicle route replanning with time windows for fruit and vegetable delivery was established, and an improved ant colony algorithm was used to resolve the model. Simulation experiment results showed that the new dispatching routing of fruit and vegetable could be optimized efficiently by using the proposed model and adopted algorithm. This research could provide theoretical support for enterprises which hoped to decrease rot loss of fruit and vegetable, increase sales income and control operating cost effectively.

  7. Chitosan nanoparticles as non-viral gene delivery vehicles based on atomic force microscopy study

    Institute of Scientific and Technical Information of China (English)

    Yujing Yuan; Jieyi Tan; Yifei Wang; Chuiwen Qian; Meiying Zhang


    Chitosan (CS), a biocompatible and biodegradable material, can act as a non-viral delivery vehicle with low toxicity. In this study, plasmid DNA (pDNA) and siRNA were encapsulated in CS nanoparticles (NPs) to prepare CS-DNA and CS-siRNA NPs using a complex coacervation process. The CS-DNA particle size was within the range of 180-370 nm with a surface charge ranging from 0 to 18 mV at pH 5.5. The stability of pDNA in CS-DNA was investigated by pDNA release study and DNase I protection assay. The release of pDNA from NPs was studied in pH 7.4 phosphatebuffered saline at 37℃ and the CS-DNA NPs could delay the DNA release. Results of DNase I protection assay showed that CS-DNA NPs could protect the encapsulated pDNA from nuclease degradation. In the transfection study, it was found that the transfection efficiency in vitro was dependent on the molecular weight, charge ratio, and DNA concentration of the CS-DNA NP as well as the type of cell transfected. Moreover, the morphology of HeLa cells transfected with CS-siRNA complexes was studied using atomic force microscopy. The results suggest that CS may be more capable than liposome in delivering siRNA to target cells. In summary,our analysis suggests that pDNA and siRNA can be encapsulated in CS NPs without being damaged.

  8. Highly stable, protein capped gold nanoparticles as effective drug delivery vehicles for amino-glycosidic antibiotics

    Energy Technology Data Exchange (ETDEWEB)

    Rastogi, Lori; Kora, Aruna Jyothi; Arunachalam, J., E-mail:


    A method for the production of highly stable gold nanoparticles (Au NP) was optimized using sodium borohydride as reducing agent and bovine serum albumin as capping agent. The synthesized nanoparticles were characterized using UV-visible spectroscopy, transmission electron microscopy, X-ray diffraction (XRD) and dynamic light scattering techniques. The formation of gold nanoparticles was confirmed from the appearance of pink colour and an absorption maximum at 532 nm. These protein capped nanoparticles exhibited excellent stability towards pH modification and electrolyte addition. The produced nanoparticles were found to be spherical in shape, nearly monodispersed and with an average particle size of 7.8 {+-} 1.7 nm. Crystalline nature of the nanoparticles in face centered cubic structure is confirmed from the selected-area electron diffraction and XRD patterns. The nanoparticles were functionalized with various amino-glycosidic antibiotics for utilizing them as drug delivery vehicles. Using Fourier transform infrared spectroscopy, the possible functional groups of antibiotics bound to the nanoparticle surface have been examined. These drug loaded nanoparticle solutions were tested for their antibacterial activity against Gram-negative and Gram-positive bacterial strains, by well diffusion assay. The antibiotic conjugated Au NP exhibited enhanced antibacterial activity, compared to pure antibiotic at the same concentration. Being protein capped and highly stable, these gold nanoparticles can act as effective carriers for drugs and might have considerable applications in the field of infection prevention and therapeutics. - Highlights: Black-Right-Pointing-Pointer Method for NaBH{sub 4} reduced and BSA capped gold nanoparticle was standardized. Black-Right-Pointing-Pointer Nanoparticles were spherical and nearly monodispersed with a size of 7.8 nm. Black-Right-Pointing-Pointer Nanoparticles are extremely stable towards pH modification and electrolyte addition. Black

  9. Optimization and evaluation of pluronic lecithin organogels as a transdermal delivery vehicle for sinomenine. (United States)

    Ba, Wenqiang; Li, Zhou; Wang, Lisheng; Wang, Ding; Liao, Weiguo; Fan, Wentao; Wu, Yinai; Liao, Fengyun; Yu, Jianye


    The purpose of the present study was to prepare and optimize sinomenine (SIN) pluronic lecithin organogels system (PLO), and to evaluate the permeability of the optimized PLO in vitro and in vivo. Box-Behnken design was used to optimize the PLO and the optimized formulation was pluronic F127 of 19.61%, lecithin of 3.60% and SIN of 1.27%. The formulation was evaluated its skin permeation and drug deposition both in vitro and in vivo compared with gel. Permeation and deposition studies of PLO were carried out with Franz diffusion cells in vitro and with microdialysis in vivo. In vitro studies, permeation rate (Jss) of SIN from PLO was 146.55 ± 2.93 μg/cm(2)/h, significantly higher than that of gel (120.39 μg/cm(2)/h) and the amount of SIN deposited in skin from the PLO was 10.08 ± 0.86 μg/cm(2), significantly larger than that from gel (6.01 ± 0.04 μg/cm(2)). In vivo skin microdialysis studies showed that the maximum concentration (Cmax) of SIN from PLO in "permeation study" and "drug-deposition study" were 150.27 ± 20.85 μg/ml and 67.95 μg/ml, respectively, both significantly higher than that of SIN from gel (29.66 and 6.73 μg/ml). The results recommend that PLO can be used as an advantageous transdermal delivery vehicle to enhance the permeation and skin deposition of SIN.

  10. Pharmacologic sensitivity of paclitaxel to its delivery vehicles drives distinct clinical outcomes of paclitaxel formulations. (United States)

    Li, Yan; Chen, Nianhang; Palmisano, Maria; Zhou, Simon


    Paclitaxel, an effective antitumor agent, is formulated in various vehicles serving as carriers to deliver the hydrophobic paclitaxel to tissue. The approved formulations in the U.S. are paclitaxel formulated in Cremophor EL (currently known as Kolliphor EL) and nanoparticle albumin-bound paclitaxel (nab-paclitaxel). Despite having the same active ingredient (paclitaxel), different formulations produce distinct products with unique efficacy and safety profiles. A semimechanistic model was developed to describe the pharmacologic sensitivity of paclitaxel under different formulations. Circulating paclitaxel concentration data from patients treated with nab-paclitaxel or Cremophor EL-paclitaxel were analyzed in NONMEM using a semimechanistic model with simultaneous disposition of paclitaxel-carrier complexes and the total paclitaxel released from the complexes. The key factors driving paclitaxel exposure in circulation and peripheral tissues were explored via sensitivity analysis. The rapid decline of total paclitaxel concentration following intravenous administration of nab-paclitaxel and Cremophor EL-paclitaxel was attributed to rapid tissue distribution of the paclitaxel-carrier complexes, with minor contribution of free and protein-bound paclitaxel. Distribution of nab-paclitaxel to peripheral tissue was 4-fold faster and 10-fold more extensive than that of Cremophor EL-paclitaxel micelles, resulting in distinct tissue paclitaxel profiles. Sensitivity analyses showed the plasma paclitaxel-time profile was insensitive to the rapid rates of tissue distribution and decomposition of paclitaxel-carrier complexes but that the tissue distribution profile of paclitaxel was highly sensitive. Tissue distribution of paclitaxel is carrier complex system-dependent. Different delivery systems result in distinct tissue paclitaxel profiles but similar paclitaxel concentration-time profiles in plasma or blood, rendering the paclitaxel plasma profile a poor surrogate for its

  11. Finding optimal solutions for vehicle routing problem with pickup and delivery services with time windows: A dynamic programming approach based on state-space-time network representations



    Optimization of on-demand transportation systems and ride-sharing services involves solving a class of complex vehicle routing problems with pickup and delivery with time windows (VRPPDTW). This paper first proposes a new time-discretized multi-commodity network flow model for the VRPPDTW based on the integration of vehicles carrying states within space-time transportation networks, so as to allow a joint optimization of passenger-to-vehicle assignment and turn-by-turn routing in congested tr...

  12. Embedding Assignment Routing Constraints through Multi Dimensional Network Construction for Solving the Multi Vehicle Routing Problem with Pickup and Delivery with Time Windows



    The multi Vehicle Routing Problem with Pickup and Delivery with Time Windows is a challenging version of the Vehicle Routing Problem. In this paper, by embedding many complex assignment routing constraints through constructing a multi dimensional network, we intend to reach optimality for local clusters derived from a reasonably large set of passengers on real world transportation networks. More specifically, we introduce a multi vehicle state space time network representation in which only t...

  13. Air Vehicle Technology Integration Program (AVTIP) Delivery Order 0008: Open Control Platform (OCP) Software Enabled Control (SEC) Hardware in the Loop Simulation Program (United States)


    AFRL-VA-WP-TR-2006-3074 AIR VEHICLE TECHNOLOGY INTEGRATION PROGRAM (AVTIP) Delivery Order 0008: Open Control Platform (OCP) Software Enabled...especially the case since the NGC technology software for SEC was completely developed in the Simulink environment. The OCP middleware was put through...STANLEY H. PRUETT GARY K. HELLMANN, Chief Aerospace Vehicles Technology Aerospace Vehicles Technology Assessment & Simulation Branch Assessment

  14. In vitro permeability of round window membrane to transforming dexamethasone with delivery vehicles-a dosage estimation

    Institute of Scientific and Technical Information of China (English)

    SUN Jian-jun; LIU Ya; KONG Wei-jia; JIANG Ping; JIANG Wei


    Background In recent years the interest of sustained drug delivery into inner ear is promising,at the same time a great deal of novel oral drugs using biodegradable vehicles have been produced to achieve sustained drug release.The aim of this study was to use biodegradable vehicles to release dexamethasone in the round window membrane application.Methods Dexamethasone gels composed of alginate and chitin were prepared and the release-permeating profiles were studied using a reproducible in vitro apparatus.A longer-period time course was simulated using the parameters acquired in this study.The data obtained in this study was compared with those of other studies in intratympanic drug delivery,and an appropriate initial dosage was extrapolated.Results The combination of alginate and chitin could efficiently restrict dexamethasone diffusion and the time course suggested a sustained drug concentration within 24 hours.A higher initial dosage was estimated to achieve a stable therapeutic concentration in vivo.Conclusion The combination of alginate and chitin could be used as vehicle for sustained release of dexamethasone in intratympanic application.

  15. Novel multifunctional pH-sensitive nanoparticles loaded into microbubbles as drug delivery vehicles for enhanced tumor targeting. (United States)

    Lv, Yongjiu; Hao, Lan; Hu, Wenjing; Ran, Ya; Bai, Yan; Zhang, Liangke


    This study fabricated novel multifunctional pH-sensitive nanoparticles loaded into microbubbles (PNP-MB) with the combined advantages of two excellent drug delivery vehicles, namely, pH-sensitive nanoparticles and microbubbles. As an antitumor drug, resveratrol (RES) was loaded into acetylated β-cyclodextrin nanoparticles (RES-PNP). The drug-loaded nanoparticles were then encapsulated into the internal space of the microbubbles. The characterization and morphology of this vehicle were investigated through dynamic light scattering and confocal laser scanning microscopy, respectively. In vitro drug release was performed to investigate the pH sensitivity of RES-PNP. The antitumor property of RES-loaded PNP-MB (RES-PNP-MB) was also analyzed in vivo to evaluate the antitumor effect of RES-PNP-MB. Results suggested that PNP exhibited pH sensitivity, and was successfully encapsulated into the microbubbles. RES-PNP-MB exhibit effective tumor growth suppressing in vivo. Therefore, such drug delivery vehicle should be of great attention in tumor therapy.

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

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


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

  17. Bone Regeneration using an Alpha 2 Beta 1 Integrin-Specific Hydrogel as a BMP-2 Delivery Vehicle (United States)

    Shekaran, Asha; García, José R.; Clark, Amy Y.; Kavanaugh, Taylor E.; Lin, Angela S.; Guldberg, Robert E.; García, Andrés J.


    Non-healing bone defects present tremendous socioeconomic costs. Although successful in some clinical settings, bone morphogenetic protein (BMP) therapies require supraphysiological dose delivery for bone repair, raising treatment costs and risks of complications. We engineered a protease-degradable poly(ethylene glycol) (PEG) synthetic hydrogel functionalized with a triple helical, α2β1 integrin-specific peptide (GFOGER) as a BMP-2 delivery vehicle. GFOGER-functionalized hydrogels lacking BMP-2 directed human stem cell differentiation and produced significant enhancements in bone repair within a critical-sized bone defect compared to RGD hydrogels or empty defects. GFOGER functionalization was crucial to the BMP-2-dependent healing response. Importantly, these engineered hydrogels outperformed the current clinical carrier in repairing non-healing bone defects at low BMP-2 doses. GFOGER hydrogels provided sustained in vivo release of encapsulated BMP-2, increased osteoprogenitor localization in the defect site, enhanced bone formation and induced defect bridging and mechanically robust healing at low BMP-2 doses which stimulated almost no bone regeneration when delivered from collagen sponges. These findings demonstrate that GFOGER hydrogels promote bone regeneration in challenging defects with low delivered BMP-2 doses and represent an effective delivery vehicle for protein therapeutics with translational potential. PMID:24726536

  18. Lipid-shelled vehicles: engineering for ultrasound molecular imaging and drug delivery. (United States)

    Ferrara, Katherine W; Borden, Mark A; Zhang, Hua


    both nano- and microdiameter particles. Targeting affinity of the microbubble can be modulated by burying the ligand within a polymer brush layer; the application of ultrasound then reveals the ligand, enabling specific targeting of only the insonified region. Microbubbles and liposomes require different strategies for both drug loading and release. Microbubble loading is inhibited by the gas core and enhanced by layer-by-layer construction or conjugation of drug-entrapped particles to the surface. Liposome loading is typically internal and is enhanced by drug-specific loading techniques. Drug release from a microbubble results from the oscillation of the gas core diameter produced by the sound wave, whereas that from a liposome is enhanced by heat produced from the local absorption of acoustic energy within the tissue microenvironment. Biological effects induced by ultrasound, such as changes in cell membrane and vascular permeability, can enhance drug delivery. In particular, as microbubbles oscillate near a vessel wall, shock waves or liquid jets enhance drug transport. Mild heating induced by ultrasound, either before or after injection of the drug, facilitates the transport of liposomes from blood vessels to the tissue interstitium, thus increasing drug accumulation in the target region. Lipid-shelled vehicles offer many opportunities for chemists and engineers; ultrasound-based applications beyond the few currently in common use will undoubtedly soon multiply as molecular construction techniques are further refined.

  19. Surface engineering of macrophages with nanoparticles to generate a cell–nanoparticle hybrid vehicle for hypoxia-targeted drug delivery

    Directory of Open Access Journals (Sweden)

    Christopher A Holden


    Full Text Available Christopher A Holden1, Quan Yuan1, W Andrew Yeudall2,3, Deborah A Lebman3,4, Hu Yang11Department of Biomedical Engineering, School of Engineering, 2Philips Institute of Oral and Craniofacial Molecular Biology, School of Dentistry, 3Massey Cancer Center, 4Department of Microbiology and Immunology, School of Medicine, Virginia Commonwealth University, Richmond, VA, USAAbstract: Tumors frequently contain hypoxic regions that result from a shortage of oxygen due to poorly organized tumor vasculature. Cancer cells in these areas are resistant to radiation- and chemotherapy, limiting the treatment efficacy. Macrophages have inherent hypoxia-targeting ability and hold great advantages for targeted delivery of anticancer therapeutics to cancer cells in hypoxic areas. However, most anticancer drugs cannot be directly loaded into macrophages because of their toxicity. In this work, we designed a novel drug delivery vehicle by hybridizing macrophages with nanoparticles through cell surface modification. Nanoparticles immobilized on the cell surface provide numerous new sites for anticancer drug loading, hence potentially minimizing the toxic effect of anticancer drugs on the viability and hypoxia-targeting ability of the macrophage vehicles. In particular, quantum dots and 5-(aminoacetamido fluoresceinlabeled polyamidoamine dendrimer G4.5, both of which were coated with amine-derivatized polyethylene glycol, were immobilized to the sodium periodate-treated surface of RAW264.7 macrophages through a transient Schiff base linkage. Further, a reducing agent, sodium cyanoborohydride, was applied to reduce Schiff bases to stable secondary amine linkages. The distribution of nanoparticles on the cell surface was confirmed by fluorescence imaging, and it was found to be dependent on the stability of the linkages coupling nanoparticles to the cell surface.Keywords: anticancer drug, cellular vehicle, confocal microscopy, dendrimer, drug delivery, hypoxia

  20. Collagen-GAG Scaffolds Grafted Onto Myocardial Infarcts in a Rat Model: A Delivery Vehicle for Mesenchymal Stem Cells

    Institute of Scientific and Technical Information of China (English)



    @@ 1 Introduction The objective of the present study was to investigate the response of rat myocardial scar tissue to type Ⅰ collagen-glycosaminoglycan (GAG) tissue engineering scaffolds, and to assess the feasibility of using a collagenGAG scaffold as a delivery vehicle for bone marrow-derived mesenchymal stem cells. The benefits of employing the collagen-GAG scaffold for this application include the following: (1) the large surface area of the three-dimensional sponge-like material allows for the delivery of a high cell density to the infarct site; (2) the scaffold allows for the localization and retention of the cells at the site of implantation; (3) the tissue response to the scaffold may promote angiogenesis at the implant site.

  1. Exactly solving the Split Pickup and Split Delivery Vehicle Routing Problem on a bike-sharing system


    Casazza, Marco


    We propose an exact methodology to solve the Split Pickup and Split Delivery Vehicle Routing Problem arising in bike-sharing systems: a bike-sharing system is a public service in which bicycles are stored in rack stations and made available for shared use to individuals on a short term basis. However, during peak hours, flows along particular direction are registered, leading to high risk of empty racks in departure stations, and full racks at destination. One of the solutions chosen by many ...

  2. Cationic cell-penetrating peptides as vehicles for siRNA delivery. (United States)

    Beloor, Jagadish; Zeller, Skye; Choi, Chang Seon; Lee, Sang-Kyung; Kumar, Priti


    RNA interference mediated gene silencing has tremendous applicability in fields ranging from basic biological research to clinical therapy. However, delivery of siRNA across the cell membrane into the cytoplasm, where the RNA silencing machinery is located, is a significant hurdle in most primary cells. Cell-penetrating peptides (CPPs), peptides that possess an intrinsic ability to translocate across cell membranes, have been explored as a means to achieve cellular delivery of siRNA. Approaches using CPPs by themselves or through incorporation into other siRNA delivery platforms have been investigated with the intent of improving cytoplasmic delivery. Here, we review the utilization of CPPs for siRNA delivery with a focus on strategies developed to enhance cellular uptake, endosomal escape and cytoplasmic localization of CPP/siRNA complexes.

  3. Delivery-flow routing and scheduling subject to constraints imposed by vehicle flows in fractal-like networks

    Directory of Open Access Journals (Sweden)

    Bocewicz Grzegorz


    Full Text Available The problems of designing supply networks and traffic flow routing and scheduling are the subject of intensive research. The problems encompass the management of the supply of a variety of goods using multi-modal transportation. This research also takes into account the various constraints related to route topology, the parameters of the available fleet of vehicles, order values, delivery due dates, etc. Assuming that the structure of a supply network, constrained by a transport network topology that determines its behavior, we develop a declarative model which would enable the analysis of the relationships between the structure of a supply network and its potential behavior resulting in a set of desired delivery-flows. The problem in question can be reduced to determining sufficient conditions that ensure smooth flow in a transport network with a fractal structure. The proposed approach, which assumes a recursive, fractal network structure, enables the assessment of alternative delivery routes and associated schedules in polynomial time. An illustrative example showing the quantitative and qualitative relationships between the morphological characteristics of the investigated supply networks and the functional parameters of the assumed delivery-flows is provided.

  4. Development of Viral Capsid DNA Aptamer Conjugates as Cell-Targeted Delivery Vehicles (United States)

    Tong, Gary Jen-Wei

    cell-targeting delivery vehicles. These agents were generated by selectively functionalizing the interior and exterior surfaces of MS2 with functional molecules and DNA aptamers, respectively, using orthogonal bioconjugation reactions. Interior surface modification was achieved through the incorporation of a uniquely-reactive cysteine residue, while exterior modification occurred via the introduction of the non-natural amino acid p-aminophenylalanine. MS2 capsids possessing interior fluorophores and exterior DNA aptamers targeted to a Jurkat T cell surface receptor were synthesized using this strategy. In cell-binding experiments, these dual-surface modified capsids were shown to bind target cells in an aptamer-dependent manner. In addition, colocalization experiments using confocal microscopy elucidated their cellular internalization pathway. Following validation of the cell-targeting capabilities of aptamer-MS2 conjugates, a multivalent photodynamic agent was developed for targeted photodynamic therapy. This agent was synthesized by installing singlet oxygen-generating porphyrins on the interior of MS2 capsids possessing DNA aptamers on the exterior. Upon illumination with 415 nm light, these dual-modified capsids were shown to generate cytotoxic singlet oxygen. In cell experiments, these agents were shown to selectively kill Jurkat cells in a heterogeneous cell mixture.

  5. Synthesis and characterization of thiolated carboxymethyl chitosan-graft-cyclodextrin nanoparticles as a drug delivery vehicle for albendazole. (United States)

    Alamdarnejad, Ghazaleh; Sharif, Alireza; Taranejoo, Shahrouz; Janmaleki, Mohsen; Kalaee, Mohammad Reza; Dadgar, Mohsen; Khakpour, Mazyar


    A new strategy for the synthesis of thiolated carboxymethyl chitosan-g-cyclodextrin nanoparticles by an ionic-gelation method is presented. The synthetic approach was based on the utilization of 1,6-hexamethylene diisocyanate during cyclodextrin grafting onto carboxymethyl chitosan. The use of the 1,6-hexamethylene diisocyanate resulted in reactions between cyclodextrin and active sites at the C6-position of chitosan, and preserved amino groups of chitosan for subsequent reactions with thioglycolic acid, as the thiolating agent, and tripolyphosphate, as the gelling counterion. Various methods such as scanning electron microscopy, rheology and in vitro release studies were employed to exhibit significant features of the nanoparticles for mucosal albendazole delivery applications. It was found that the thiolated carboxymethyl chitosan-g-cyclodextrin nanoparticles prepared using an aqueous solution containing 1 wt% of tripolyphosphate and having 115.65 (μmol/g polymer) of grafted thiol groups show both the highest mucoadhesive properties and the highest albendazole entrapment efficiency. The latter was confirmed theoretically by calculating the enthalpy of mixing of albendazole in the above thiolated chitosan polymer.

  6. Biodegradable nanoparticles are excellent vehicle for site directed in-vivo delivery of drugs and vaccines

    National Research Council Canada - National Science Library

    Mahapatro, Anil; Singh, Dinesh K


    Biodegradable nanoparticles (NPs) are gaining increased attention for their ability to serve as a viable carrier for site specific delivery of vaccines, genes, drugs and other biomolecules in the body...

  7. Single-walled carbon nanotubes as delivery vehicles enhance the immunoprotective effects of a recombinant vaccine against Aeromonas hydrophila. (United States)

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


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

  8. Research of Delivery Towing methods for Metro Vehicles%地铁车辆回送方法的研究

    Institute of Scientific and Technical Information of China (English)

    厉砚磊; 何宝昌


    制动系统是城市轨道交通车辆的关键系统之一,其工作可靠性直接关系到列车的运行安全。回送试验是保证地铁车辆安全押运的重要环节,本文阐述了地铁车辆各个制动系统的回送工作原理、回送管路铺设和连接方法,并总结了地铁车辆在回送试验和押运过程中的注意事项。%As a critical system for urban rail transit vehicle, the brake system involves the reliable and safe operation of a train, and delivery towing testing is therefore a necessary step for the safe transportation of metro vehicles. This paper outlines the principles of various brake system used in metro cars, laying and connection of temporary brake pipes during the delivery towing operation, along with the precautions which should be taken for the transportation.

  9. Hyaluronidase enzyme core-5-fluorouracil-loaded chitosan-PEG-gelatin polymer nanocomposites as targeted and controlled drug delivery vehicles. (United States)

    Rajan, M; Raj, V; Al-Arfaj, Abdullah A; Murugan, A M


    This study examines the performance of novel hyaluronidase enzyme core-5-fluorouracil-loaded chitosan-polyethylene glycol-gelatin polymer nanocomposites, which were prepared using an ionic gelation technique, as targeted and controlled drug delivery vehicles. These hyaluronidase-loaded nanoparticles have recently been proposed as targeted and controlled drug delivery vehicle systems to tissues due to their ability to loosen the intercellular connective matrix of hyaluronic acid. The encapsulation efficiency and loading capacities of the nanoparticles demonstrated that these nanocomposites displayed sufficient binding ability, which depends on the pH and initial concentration of the drug. The cytotoxic effects of the chitosan-hyaluronidase-5-fluorouracil (CS-HYL-5-FU), chitosan-hyaluronidase-5-fluorouracil polyethylene glycol (CS-HYL-5-FU-PEG), and chitosan-hyaluronidase-5-fluorouracil polyethylene glycol-gelatin (CS-HYL-5-FU-PEG-G) nanoparticles were assessed using MTT assays, and the nanovectors were found to be less cytotoxic than the chemotherapeutic 5-FU after incubation for 3-12h. The particle sizes of the CS-HYL-5-FU, CS-HYL-5-FU-PEG and CS-HYL-5-FU-PEG-G polymer composites were between 300 and 580 nm, as determined by a Zetasizer. Scanning electron microscopy (SEM) analysis indicated that the nanocomposites exhibit a clear, smooth surface and fine morphology. Linkages of the polymers, enzyme, and drug were confirmed by FTIR spectroscopy. Atomic fluorescence microscopy (AFM) analysis confirmed the size of the polymer composite nanoparticles. Therefore, this work established that the drug can be successfully encapsulated in chitosan-polyethylene glycol-gelatin-accompanied hyaluronidase nanoparticles with a homogeneous distribution. These nanoparticles can be potential carriers for targeted and controlled drug delivery to cancer cells.

  10. Dendrimers: General Aspects, Applications and Structural Exploitations as Prodrug/ Drug-delivery Vehicles in Current Medicine. (United States)

    Mariyam, Merina; Ghosal, Kajal; George, Anne; Thomas, Sabu; Kalarikkal, Nandakumar; S Latha, Mahima


    Dendrimers are hyper branched macro molecules with well-defined structure and high degree of functionality on the surface. The dendrimer architecture allows control over properties such as shape, size, density, polarity, reactivity, solubility etc. This can be manipulated to design molecules with desired properties in biomedical applications. Recent advancement in correlating structure to biodegradability and invivo performance opens up new avenue for these molecules in biological applications like drug delivery and tissue engineering. The unique structure of dendrimers provides enough attachment sites for drugs in drug delivery applications. It is possible to tune the molecule in such a way as to encapsulate drug molecule outside target area and release in the local environment of targets. This review presents the general aspects of dendrimers and how these properties are exploited for drug delivery applications. Copyright© Bentham Science Publishers; For any queries, please email at

  11. An Ant Colony Optimization and Hybrid Metaheuristics Algorithm to Solve the Split Delivery Vehicle Routing Problem (United States)


    subsection 4 provides an overview of the benchmark data sets for the SDVRP. 3 2.1 SDVRP Formulation According to Aleman et al. (2010), the...variants of the vehicle routing problem. 24 References Aleman , R.E., Zhang, X., Hill, R. R., 2010. An adaptive memory algorithm for the split

  12. DNA origami as an in vivo drug delivery vehicle for cancer therapy. (United States)

    Zhang, Qian; Jiang, Qiao; Li, Na; Dai, Luru; Liu, Qing; Song, Linlin; Wang, Jinye; Li, Yaqian; Tian, Jie; Ding, Baoquan; Du, Yang


    Many chemotherapeutics used for cancer treatments encounter issues during delivery to tumors in vivo and may have high levels of systemic toxicity due to their nonspecific distribution. Various materials have been explored to fabricate nanoparticles as drug carriers to improve delivery efficiency. However, most of these materials suffer from multiple drawbacks, such as limited biocompatibility and inability to engineer spatially addressable surfaces that can be utilized for multifunctional activity. Here, we demonstrate that DNA origami possessed enhanced tumor passive targeting and long-lasting properties at the tumor region. Particularly, the triangle-shaped DNA origami exhibits optimal tumor passive targeting accumulation. The delivery of the known anticancer drug doxorubicin into tumors by self-assembled DNA origami nanostructures was performed, and this approach showed prominent therapeutic efficacy in vivo. The DNA origami carriers were prepared through the self-assembly of M13mp18 phage DNA and hundreds of complementary DNA helper strands; the doxorubicin was subsequently noncovalently intercalated into these nanostructures. After conducting fluorescence imaging and safety evaluation, the doxorubicin-containing DNA origami exhibited remarkable antitumor efficacy without observable systemic toxicity in nude mice bearing orthotopic breast tumors labeled with green fluorescent protein. Our results demonstrated the potential of DNA origami nanostructures as innovative platforms for the efficient and safe drug delivery of cancer therapeutics in vivo.

  13. Mucosal vaccines: a paradigm shift in the development of mucosal adjuvants and delivery vehicles. (United States)

    Srivastava, Atul; Gowda, Devegowda Vishakante; Madhunapantula, SubbaRao V; Shinde, Chetan G; Iyer, Meenakshi


    Mucosal immune responses are the first-line defensive mechanisms against a variety of infections. Therefore, immunizations of mucosal surfaces from which majority of infectious agents make their entry, helps to protect the body against infections. Hence, vaccinization of mucosal surfaces by using mucosal vaccines provides the basis for generating protective immunity both in the mucosal and systemic immune compartments. Mucosal vaccines offer several advantages over parenteral immunization. For example, (i) ease of administration; (ii) non-invasiveness; (iii) high-patient compliance; and (iv) suitability for mass vaccination. Despite these benefits, to date, only very few mucosal vaccines have been developed using whole microorganisms and approved for use in humans. This is due to various challenges associated with the development of an effective mucosal vaccine that can work against a variety of infections, and various problems concerned with the safe delivery of developed vaccine. For instance, protein antigen alone is not just sufficient enough for the optimal delivery of antigen(s) mucosally. Hence, efforts have been made to develop better prophylactic and therapeutic vaccines for improved mucosal Th1 and Th2 immune responses using an efficient and safe immunostimulatory molecule and novel delivery carriers. Therefore, in this review, we have made an attempt to cover the recent advancements in the development of adjuvants and delivery carriers for safe and effective mucosal vaccine production. © 2015 APMIS. Published by John Wiley & Sons Ltd.

  14. Liposomes : Vehicles for the targeted and controlled delivery of peptides and proteins

    NARCIS (Netherlands)

    Crommelin, DJA; Daemen, T; Scherphof, GL; Vingerhoeds, MH; Heeremans, JLM; Kluft, C; Storm, G


    Several approaches are presented that have been developed for the liposomal delivery of peptides and proteins. For a rational design of targeted liposomes, the anatomical and physiological constraints with respect to the distribution of liposomes in the body have to be taken into account. Target sit

  15. Pick-Up and Delivery Problem: Models and Single Vehicle Exact Procedures, (United States)


    appropriate Lagrangian ascent procedures (for example, see Bazaraa and Goode 18)). IMI 22 U r! ,.~ 4. A BRANCH AND BOUND ALGORITHM FOR THE SINGLE VEHICLE...B&B phase. For this purpose a subgradient optimization procedure, suggested by Bazaraa and Goode for the TSP, was utilized to improve the * value of F...Analysed by a Routing Heuristic", Working Paper #81-006, University of Maryland (February). 8 Bazaraa , M. and J. Goode (1977). "The Travelling Salesman

  16. Transdermal delivery of ondansetron hydrochloride: effects of vehicles and penetration enhancers. (United States)

    Gwak, Hye Sun; Oh, Ik Sang; Chun, In Koo


    The effects of vehicles and penetration enhancers on the in vitro permeation of ondansetron hydrochloride (OS) across dorsal hairless mouse skins were investigated. Various types of vehicles, including ester, alcohol, and ether and their mixtures were used, and then a series of fatty acids and fatty alcohols were employed as enhancers. Among pure vehicles used, water and ethanol showed high permeation fluxes, which were 48.2+/-23.7 and 41.9+/-17.9 microg/cm2 per h, respectively. Even though propylene glycol monocaprylate (PGMC) alone did not show a high permeation rate, the skin permeability of OS was increased by the addition of diethylene glycol monoethyl ether (DGME); the highest flux was achieved at 40% of DGME. Also, the combination of PGMC and ethanol (80:20) or PGMC and propylene glycol (PG) (60:40) increased the permeation flux by six- and two-fold, respectively, compared to PGMC alone. The synergistic enhancement was also obtained by using PG-oleyl alcohol (OAl) cosolvent. The greatest flux was attained by the addition of unsaturated fatty acids at 3% concentration to PG. The enhancement factors with the addition of oleic acid or linoleic acid to PG were about 1250 and 450, respectively. But saturated fatty acids failed to show a significant enhancing effect. When the PGMC-DGME (60:40) cosolvent system was used as a vehicle, all fatty acids, including unsaturated fatty acids, failed to show significant enhancing effects. The results indicate that the combinations of oleic acid, linoleic acid, or oleyl alcohol with PG, or PGMC-DGME (60:40) cosolvent could be used for the design of the OS transdermal system.

  17. Vehicle Minimization for the Multimodal Pickup and Delivery Problem with Time Windows (United States)


    problems for parallel machines. The VRP solved is subject to time windows and capacity constraints on vehicles and offloading. The VRP is multimodal. The...addresses a special case of the VRP . The VRP considered is multimodal with time constraints. It is also subject to capacity constraints, both on...Consequently, the problem can also be considered to be a special case of the Fleet Size and Mix Problem. The primary issue in solving any VRP is

  18. Conceptual Design of New Energy Delivery Vehicles%新能源递送车辆概念化设计

    Institute of Scientific and Technical Information of China (English)

    张建雄; 彭娟; 钮峥恺; 寇博


    New energy concept car in order to highlight the “new energy” and “concept”, locates in the shuttle in the city of roadway with the new concept of energy and delivery mode for the characteristics of small courier delivery vehicles. On the basis of the domestic current situation and prospect of new energy vehicles, it is combined with the existing technology and concepts, and puts forward the design concept of future delivery vehicles. Based on the existing automobile industry, new energy technology and contemporary art design style of investigation and study, to locate in the city logistics concept vehicles and their logistics scheme has carried on the technical aspects of unmanned aerial vehicle and the public demand side argument; Using the principle of bionics and car design process has carried on the conceptual design. Through this topic research design, the concept of new energy automotive design task. Modeling beauty and reached the expected use demand, has certain market potential and application promotion value.%新能源概念汽车以突出“新能源”与“概念”为主,定位于穿梭在城市巷道的以新能源和概念递送方式为特点的小型快递递送车辆。该种车辆以节能高效和具有未来概念造型为特点,依据目前国内新能源汽车的发展现状和前景,是以现有技术和概念技术结合,而提出的设计一种未来概念递送车辆的课题。通过对现有汽车工业技术、新能源技术和当代艺术设计风格的调查研究,对定位于城市物流车辆及其概念物流无人机的方案进行了技术方面和大众需求方面的论证;利用自然生长的有机结构形态原理完成了概念性设计;通过工业设计程序与方法中的提案方法进行方案评估。通过本课题研究设计,完成了新能源汽车概念化设计任务,达到了预想的造型美感和使用需求,具有一定的市场潜力和应用推广价值。

  19. Poly(ester amide-Poly(ethylene oxide Graft Copolymers: Towards Micellar Drug Delivery Vehicles

    Directory of Open Access Journals (Sweden)

    Gregory J. Zilinskas


    Full Text Available Micelles formed from amphiphilic copolymers are promising materials for the delivery of drug molecules, potentially leading to enhanced biological properties and efficacy. In this work, new poly(ester amide-poly(ethylene oxide (PEA-PEO graft copolymers were synthesized and their assembly into micelles in aqueous solution was investigated. It was possible to tune the sizes of the micelles by varying the PEO content of the polymers and the method of micelle preparation. Under optimized conditions, it was possible to obtain micelles with diameters less than 100 nm as measured by dynamic light scattering and transmission electron microscopy. These micelles were demonstrated to encapsulate and release a model drug, Nile Red, and were nontoxic to HeLa cells as measured by an MTT assay. Overall, the properties of these micelles suggest that they are promising new materials for drug delivery systems.

  20. Poly(Lactic Acid) Nanoparticles Targeting α5β1 Integrin as Vaccine Delivery Vehicle, a Prospective Study (United States)

    Gutjahr, Alice; Terrat, Céline; Exposito, Jean-Yves; Verrier, Bernard; Lethias, Claire


    Biodegradable polymeric nanoparticles are vehicles of choice for drug delivery and have the ability to encapsulate and present at their surface different molecules of interest. Among these bio-nanocarriers, poly(lactic acid) (PLA) nanoparticles have been used as adjuvant and vehicle for enhanced vaccine efficacy. In order to develop an approach to efficient vaccine delivery, we developed nanoparticles to target α5β1 positive cells. We first overproduced, in bacteria, human fibronectin FNIII9/10 recombinant proteins possessing an integrin α5β1 binding site, the RGDS sequence, or a mutated form of this site. After having confirmed the integrin binding properties of these recombinant proteins in cell culture assays, we were able to formulate PLA nanoparticles with these FNIII9/10 proteins at their surface. We then confirmed, by fluorescence and confocal microscopy, an enhanced cellular uptake by α5β1+ cells of RGDS-FNIII9/10 coated PLA nanoparticles, in comparison to KGES-FNIII9/10 coated or non-coated controls. As a first vaccination approach, we prepared PLA nanoparticles co-coated with p24 (an HIV antigen), and RGDS- or KGES-FNIII9/10 proteins, followed by subcutaneous vaccine administration, in mice. Although we did not detect improvements in the apparent humoral response to p24 antigen in the serum of RGDS/p24 nanoparticle-treated mice, the presence of the FNIII proteins increased significantly the avidity index of anti-p24 antibodies compared to p24-nanoparticle-injected control mice. Future developments of this innovative targeted vaccine are discussed. PMID:27973577

  1. Thiolated methylated dimethylaminobenzyl chitosan: A novel chitosan derivative as a potential delivery vehicle. (United States)

    Hakimi, Shirin; Mortazavian, Elaheh; Mohammadi, Zohreh; Samadi, Fatemeh Yazdi; Samadikhah, Hamidreza; Taheritarigh, Sadegh; Tehrani, Niyousha Rafiee; Rafiee-Tehrani, Morteza


    Chitosan is a natural mucoadhesive, biodegradable, biocompatible and nontoxic polymer which has been used in pharmaceutical industry for a lot of purposes such as dissolution enhancing, absorption enhancing, sustained releasing and protein, gene or drug delivery. Two major disadvantages of chitosan are poor solubility in physiological pH and low efficiency for protein and gene delivery. In this study thiolated methylated N-(4-N,N-dimethylaminobenzyl) chitosan was prepared for the first time in order to improve the solubility and delivery properties of chitosan. This novel chitosan derivative was characterized using (1)H NMR, Ellman test, TGA and Zetasizer. Cell toxicity studies were performed on Human Embryonic Kidney 293 (Hek293) cell line using XTT method, to investigate the potential effect of this new derivative on cell viability. (1)H NMR results showed that all substitution reactions were successfully carried out. Zeta potential of new derivative at acidic and physiological pHs was greater than chitosan and it revealed an increase in solubility of the derivative. Furthermore, it had no significant cytotoxicity against Hek293 cell line in comparison to chitosan. These findings confirm that this new derivative can be introduced as a suitable compound for biomedical purposes. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Functional Polymeric Systems as Delivery Vehicles for Methylene Blue in Photodynamic Therapy. (United States)

    Junqueira, Mariana V; Borghi-Pangoni, Fernanda B; Ferreira, Sabrina B S; Rabello, Bruno R; Hioka, Noboru; Bruschi, Marcos L


    Antibiotic-resistant microorganisms have become a global concern, and the search for alternative therapies is very important. Photodynamic therapy (PDT) consists of the use of a nontoxic photosensitizer (PS), light, and oxygen. This combination produces reactive oxygen species and singlet oxygen, which can alter cellular structures. Methylene blue (MB) is a substance from the phenothiazine class often used as a PS. In this work, to facilitate the PS contact within the wounds, we have used Design of Experiments 2(3) plus central point to develop functional polymeric systems. The formulations were composed by poloxamer 407 [15.0, 17.5, or 20.0% (w/w)], Carbopol 934P [0.15, 0.20, or 0.25% (w/w)], and MB [0.25, 0.50, or 0.75% (w/w)]. The sol-gel transition temperature, flow rheometry, in vitro MB release, and ex vivo study of MB cutaneous permeation and retention were investigated. Moreover, the evaluation of photodynamic activity was also analyzed by in vitro degradation of tryptophan by singlet oxygen and using Artemia salina. The determination of the gelation temperature displayed values within the range of 25-37 °C, and the systems with better characteristics were subjected to rheological analysis and in vitro release profiling. The 20/0.15/0.25 formulation showed the best release profile (42.57% at 24 h). This system displayed no significant skin permeation (0.38% at 24 h), and the photooxidation of tryptophan test showed the production of reactive species of oxygen. The toxicity test using A. salina revealed that the MB associated with the light increased the mortality rate by 61.29%. Therefore, investigating the PDT efficacy of the functional polymeric system containing MB will be necessary in the future.

  3. Concept for a Lunar Transfer Vehicle for Small Satellite Delivery to the Moon from the International Space Station (United States)

    Elliott, John; Alkalai, Leon


    The International Space Station (ISS) has developed as a very capable center for scientific research in Lower Earth Orbit. An additional potential of the ISS that has not thus far been exploited, is the use of this orbiting plat-form for the assembly and launching of vehicles that could be sent to more distant destinations. This paper reports the results of a recent study that looked at an architecture and conceptual flight system design for a lunar transfer vehicle (LTV) that could be delivered to the ISS in segments, assembled, loaded with payload and launched from the ISS with the objective of delivering multiple small and micro satellites to lunar orbit. The design of the LTV was optimized for low cost and high payload capability, as well as ease of assembly. The resulting design would use solar electric propulsion (SEP) to carry a total payload mass of 250 kg from the ISS to a 100 km lunar orbit. A preliminary concept of operations was developed considering currently available delivery options and ISS capabili-ties that should prove flexible enough to accommodate a variety of payloads and missions. This paper will present an overview of the study, including key trades, mission and flight system design, and notional operational concept.

  4. Assessing the Battery Cost at Which Plug-In Hybrid Medium-Duty Parcel Delivery Vehicles Become Cost-Effective

    Energy Technology Data Exchange (ETDEWEB)

    Ramroth, L. A.; Gonder, J. D.; Brooker, A. D.


    The National Renewable Energy Laboratory (NREL) validated diesel-conventional and diesel-hybrid medium-duty parcel delivery vehicle models to evaluate petroleum reductions and cost implications of hybrid and plug-in hybrid diesel variants. The hybrid and plug-in hybrid variants are run on a field data-derived design matrix to analyze the effect of drive cycle, distance, engine downsizing, battery replacements, and battery energy on fuel consumption and lifetime cost. For an array of diesel fuel costs, the battery cost per kilowatt-hour at which the hybridized configuration becomes cost-effective is calculated. This builds on a previous analysis that found the fuel savings from medium duty plug-in hybrids more than offset the vehicles' incremental price under future battery and fuel cost projections, but that they seldom did so under present day cost assumptions in the absence of purchase incentives. The results also highlight the importance of understanding the application's drive cycle specific daily distance and kinetic intensity.


    Institute of Scientific and Technical Information of China (English)

    WANG Enrong; YING Liang; WANG Wanjun; RAKHEJA Subhash; SU Chunyi


    The design and analysis of an intelligent vehicle suspension with MR dampers should address hybrid semi-active control goals, such as rejection of current-switching discontinuity and MR-damper hysteresis, asymmetric damping from the symmetric MR-damper design, robustness on the vehicle operation parameter uncertainties and consideration of essential multiple suspension goals. Following the proposed skyhook-based asymmetric semi-active controller (Part Ⅰ) for achieving the above goals, herein, a set of suspension performance measures and three kinds of varying amplitude harmonic, rounded pulse and really measured random excitations are systematically defined, and the sensitivity of quarter-vehicle MR-suspension performance to variations in operating conditions is thoroughly analyzed. The results illustrate that the proposed skyhook-based semi-active MR-suspension in the asymmetric mode yields relatively superior dynamic responses to meet the multiple suspension performances of ride, rattle space, road-holding and dynamic tire force transmitted to the pavement, and has desirable robustness on variations in operating conditions of vehicle load and speed and the road roughness.

  6. Inclusion bodies as potential vehicles for recombinant protein delivery into epithelial cells

    Directory of Open Access Journals (Sweden)

    Liovic Mirjana


    Full Text Available Abstract Background We present the potential of inclusion bodies (IBs as a protein delivery method for polymeric filamentous proteins. We used as cell factory a strain of E. coli, a conventional host organism, and keratin 14 (K14 as an example of a complex protein. Keratins build the intermediate filament cytoskeleton of all epithelial cells. In order to build filaments, monomeric K14 needs first to dimerize with its binding partner (keratin 5, K5, which is then followed by heterodimer assembly into filaments. Results K14 IBs were electroporated into SW13 cells grown in culture together with a “reporter” plasmid containing EYFP labeled keratin 5 (K5 cDNA. As SW13 cells do not normally express keratins, and keratin filaments are built exclusively of keratin heterodimers (i.e. K5/K14, the short filamentous structures we obtained in this study can only be the result of: a if both IBs and plasmid DNA are transfected simultaneously into the cell(s; b once inside the cells, K14 protein is being released from IBs; c released K14 is functional, able to form heterodimers with EYFP-K5. Conclusions Soluble IBs may be also developed for complex cytoskeletal proteins and used as nanoparticles for their delivery into epithelial cells.

  7. Dendrimer-magnetic nanoparticles as multiple stimuli responsive and enzymatic drug delivery vehicle

    Energy Technology Data Exchange (ETDEWEB)

    Chandra, Sudeshna; Noronha, Glen [Metallurgical and Materials Science Department, Indian Institute of Technology Bombay, Powai, Mumbai, 400076 (India); Dietrich, Sascha; Lang, Heinrich [Technische Universität Chemnitz, Institute of Chemistry, Straße der Nationen 62, d-09111 Chemnitz (Germany); Bahadur, Dhirendra, E-mail: [Metallurgical and Materials Science Department, Indian Institute of Technology Bombay, Powai, Mumbai, 400076 (India)


    Two different chain lengths of (poly)ethylene glycol-PAMAM dendrimers namely, L6-PEG-PAMAM and S6-PEG-PAMAM with six end-grafted ethylene glycol ether-tentacles of type CH{sub 2}CH{sub 2}C(O)O(CH{sub 2}CH{sub 2}O){sub 9}CH{sub 3} and CH{sub 2}CH{sub 2}C(O)O(CH{sub 2}CH{sub 2}O){sub 2}C{sub 2}H{sub 5}, respectively, were synthesized. These dendrimers have multiple σ-donor capabilities and therefore, were used for stabilizing the magnetite (Fe{sub 3}O{sub 4}) nanoparticles. Both the dendrimer-magnetic nanoparticles (L6-PEG-PAMAM-MNPs and S6-PEG-PAMAM-MNPs) were characterized by different spectroscopic and microstructural techniques. The nanoparticles were mesoporous and superparamagnetic and therefore, explored for their possible use in delivery of cancer drug, doxorubicin (DOX). In the developed drug delivery system, achieving high drug-loading efficiency with controllable release were the main challenges. The change in zeta potential and quenching of fluorescence intensity suggests chemical interaction between DOX and the nanoparticles. The loading efficiency was calculated to be over 95% with a sustained pH and temperature sensitive release. Further, enzyme cathepsin B has also been used to degrade the dendritic shell to trigger sustained drug release in the vicinity of tumor cells.

  8. Low-density lipoprotein peptide-combined DNA nanocomplex as an efficient anticancer drug delivery vehicle. (United States)

    Zhang, Nan; Tao, Jun; Hua, Haiying; Sun, Pengchao; Zhao, Yongxing


    DNA is a type of potential biomaterials for drug delivery due to its nanoscale geometry, loading capacity of therapeutics, biocompatibility, and biodegradability. Unfortunately, DNA is easily degraded by DNases in the body circulation and has low intracellular uptake. In the present study, we selected three cationic polymers polyethylenimine (PEI), hexadecyl trimethyl ammonium bromide (CTAB), and low-density lipoprotein (LDL) receptor targeted peptide (RLT), to modify DNA and improve the issues. A potent anti-tumor anthracycline-doxorubicin (DOX) was intercalated into DNA non-covalently and the DOX/DNA was then combined with PEI, CTAB, and RLT, respectively. Compact nanocomplexes were formed by electrostatic interaction and could potentially protect DNA from DNases. More importantly, RLT had the potential to enhance intracellular uptake by LDL receptor mediated endocytosis. In a series of in vitro experiments, RLT complexed DNA enhanced intracellular delivery of DOX, increased tumor cell death and intracellular ROS production, and reduced intracellular elimination of DOX. All results suggested that the easily prepared and targeted RLT/DNA nanocomplexes had great potential to be developed into a formulation for doxorubicin with enhanced anti-tumor activity.

  9. Inclusion bodies as potential vehicles for recombinant protein delivery into epithelial cells. (United States)

    Liovic, Mirjana; Ozir, Mateja; Zavec, Apolonija Bedina; Peternel, Spela; Komel, Radovan; Zupancic, Tina


    We present the potential of inclusion bodies (IBs) as a protein delivery method for polymeric filamentous proteins. We used as cell factory a strain of E. coli, a conventional host organism, and keratin 14 (K14) as an example of a complex protein. Keratins build the intermediate filament cytoskeleton of all epithelial cells. In order to build filaments, monomeric K14 needs first to dimerize with its binding partner (keratin 5, K5), which is then followed by heterodimer assembly into filaments. K14 IBs were electroporated into SW13 cells grown in culture together with a "reporter" plasmid containing EYFP labeled keratin 5 (K5) cDNA. As SW13 cells do not normally express keratins, and keratin filaments are built exclusively of keratin heterodimers (i.e. K5/K14), the short filamentous structures we obtained in this study can only be the result of: a) if both IBs and plasmid DNA are transfected simultaneously into the cell(s); b) once inside the cells, K14 protein is being released from IBs; c) released K14 is functional, able to form heterodimers with EYFP-K5. Soluble IBs may be also developed for complex cytoskeletal proteins and used as nanoparticles for their delivery into epithelial cells.

  10. Inclusion bodies as potential vehicles for recombinant protein delivery into epithelial cells (United States)


    Background We present the potential of inclusion bodies (IBs) as a protein delivery method for polymeric filamentous proteins. We used as cell factory a strain of E. coli, a conventional host organism, and keratin 14 (K14) as an example of a complex protein. Keratins build the intermediate filament cytoskeleton of all epithelial cells. In order to build filaments, monomeric K14 needs first to dimerize with its binding partner (keratin 5, K5), which is then followed by heterodimer assembly into filaments. Results K14 IBs were electroporated into SW13 cells grown in culture together with a “reporter” plasmid containing EYFP labeled keratin 5 (K5) cDNA. As SW13 cells do not normally express keratins, and keratin filaments are built exclusively of keratin heterodimers (i.e. K5/K14), the short filamentous structures we obtained in this study can only be the result of: a) if both IBs and plasmid DNA are transfected simultaneously into the cell(s); b) once inside the cells, K14 protein is being released from IBs; c) released K14 is functional, able to form heterodimers with EYFP-K5. Conclusions Soluble IBs may be also developed for complex cytoskeletal proteins and used as nanoparticles for their delivery into epithelial cells. PMID:22624805

  11. Lipid nano/submicron emulsions as vehicles for topical flurbiprofen delivery. (United States)

    Fang, Jia-You; Leu, Yann-Lii; Chang, Chia-Chun; Lin, Chia-Hsuan; Tsai, Yi-Hung


    The application of lipid nano/submicron emulsions as topical drug carrier systems for the percutaneous absorption of flurbiprofen was investigated. The lipid emulsions were made up of isopropyl myristate (IPM), soybean oil, or coconut oil as the oil phase, egg lecithin as the predominant emulsifier, and double-distilled water as the external phase. Stearylamine (SA) and deoxycholic acid (DA) also were used to produce positively and negatively charged emulsions. To evaluate the physicochemical properties of the lipid emulsions, particle size by laser light scattering, the image of atomic force microscopy, and relaxation time values by Nuclear Magnetic Resonance (NMR) were determined. The in vitro permeation data showed that incorporation of SA significantly reduced the topical delivery of flurbiprofen. On the other hand, incorporation of DA exhibited no or a negligible effect on drug permeation. Enhancement of drug absorption was observed when adding oleic acid as part of the oil phase. The in vivo topical application of flurbiprofen from selected lipid emulsions showed a similar trend to the in vitro status. Furthermore, the intersubject variability was considerably reduced by lipid emulsions than by aqueous suspensions in both the in vitro and in vivo experiments. The irritant profiles of lipid emulsions showed that IPM elicited higher irritation than soybean oil. The incorporation of oleic acid also produced skin disruption. The results in the present study suggest the feasibility of lipid emulsions for the topical delivery of flurbiprofen.

  12. Mesenchymal stem cells as novel micro-ribonucleic acid delivery vehicles in kidney disease. (United States)

    Yao, Kevin; Ricardo, Sharon D


    MicroRNAs (miRNAs) are short single strands of RNA responsible for post-transcriptional regulation of gene expression and have been implicated in the pathogenesis of chronic kidney disease (CKD). Emerging evidence reports that miRNAs can reduce kidney fibrosis through regulation of targets associated with collagen and extracellular matrix accumulation. However, the development of miRNA therapies has been hampered by the lack of targeted and sustainable methods of systemic miRNA delivery. Mesenchymal stem cells (MSCs) provide a promising miRNA delivery platform to overcome toxicity, the potential for insertional mutations and the low efficiency of previous methods. MSCs are endogenously immunoprivileged and home to sites of inflammation. They also release trophic growth factors to modulate the immune system, alter the polarization of macrophages and provide renal protection and repair. The potential to engineer MSCs to express or overexpress miRNAs, released by exosomes, may enhance their natural functions. Clinical studies are already being conducted individually for the use of miRNAs in cancer and MSCs in diseases associated with CKD. Hence, the combination of miRNAs and MSCs may provide an unparalleled cell-based therapy for treating CKD.

  13. Microencapsulated foods as a functional delivery vehicle for omega-3 fatty acids: a pilot study

    Directory of Open Access Journals (Sweden)

    David Robert M


    Full Text Available Abstract It is well established that the ingestion of the omega-3 (N3 fatty acids docosahexaenoic acid (DHA and eicosapentaenoic acid (EPA positively benefit a variety of health indices. Despite these benefits the actual intake of fish derived N3 is relatively small in the United States. The primary aim of our study was to examine a technology capable of delivering omega-3 fatty acids in common foods via microencapsulation (MicroN3 in young, healthy, active participants who are at low risk for cardiovascular disease. Accordingly, we randomized 20 participants (25.4 ± 6.2 y; 73.4 ± 5.1 kg to receive the double blind delivery of a placebo-matched breakfast meal (~2093 kJ containing MicroN3 (450–550 mg EPA/DHA during a 2-week pilot trial. Overall, we observed no differences in overall dietary macronutrient intake other than the N3 delivery during our treatment regimen. Post-test ANOVA analysis showed a significant elevation in mean (SE plasma DHA (91.18 ± 9.3 vs. 125.58 ± 11.3 umol/L; P

  14. Chitosan-Poly (I:C-PADRE Based Nanoparticles as Delivery Vehicles for Synthetic Peptide Vaccines

    Directory of Open Access Journals (Sweden)

    Jorge F. Correia-Pinto


    Full Text Available The safety and precision of peptide antigens has prompted the search for adjuvants capable of increasing the immune response against these intrinsically poorly immunogenic antigens. The integration of both immunostimulants and peptide antigens within nanometric delivery systems for their co-delivery to immune cells is a promising vaccination strategy. With this in mind, the potential synergistic effect of the immunostimulant poly (I:C (pIC and a T-Helper peptide (PADRE, integrated into a chitosan (CS based nanostructure, was explored. The value of this nanostructured combination of materials was assessed for a peptide antigen (1338aa derived from the HPV-16 L2 protein. These nanoparticles, produced by ionic gelation technique, exhibited a nanometric size (<300 nm, a high positive surface charge (>40 mV and high pIC association efficiency (>96%. They also showed capacity for the association of both the 1338aa and PADRE peptides. The influence of the presence of pIC and PADRE in the nanocomposition, as well as that of the peptide presentation form (encapsulated versus surface adsorbed on the antibody induction was evaluated in a preliminary in vivo study. The data obtained highlights the possibility to engineer nanoparticles through the rational combination of a number of adjuvant molecules together with the antigen.

  15. Poly methacrylic acid modified CDHA nanocomposites as potential pH responsive drug delivery vehicles. (United States)

    Victor, Sunita Prem; Sharma, Chandra P


    The objective of this study was to prepare pH sensitive polymethacrylic acid-calcium deficient hydroxyapatite (CDHA) nanocomposites. The CDHA nanoparticles were prepared by coprecipitation method. The modification of CDHA by methacrylic acid (MA) was achieved by AIBN initiated free radical polymerization with sodium bisulphite as catalyst followed by emulsion technique. These nanocomposites with a half life of 8h consisted of high aspect ratio, needle like particles and exhibited an increase in swelling behaviour with pH. The in vivo potential of the nanocomposites was evaluated in vitro by the results of cell aggregation, protein adsorption, MTT assay and haemolytic activity. The invitro loading and release studies using albumin as a model drug indicate that the nanocomposites gave better loading when compared to the CDHA nanoparticles and altered the drug release rates. The nanocomposites also exhibited good uptake on C6 glioma cells as studied by fluorescence microscopy. The results obtained suggest that these nanocomposites have great potential for oral controlled protein delivery and can be extended further for intracellular drug delivery applications.

  16. Polyethylenimine-grafted cellulose nanofibril aerogels as versatile vehicles for drug delivery. (United States)

    Zhao, Jiangqi; Lu, Canhui; He, Xu; Zhang, Xiaofang; Zhang, Wei; Zhang, Ximu


    Aerogels from polyethylenimine-grafted cellulose nanofibrils (CNFs-PEI) were developed for the first time as a novel drug delivery system. The morphology and structure of the CNFs before and after chemical modification were characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS). Water-soluble sodium salicylate (NaSA) was used as a model drug for the investigation of drug loading and release performance. The CNFs-PEI aerogels exhibited a high drug loading capability (287.39 mg/g), and the drug adsorption process could be well described by Langmuir isotherm and pseudo-second-order kinetics models. Drug release experiments demonstrated a sustained and controlled release behavior of the aerogels highly dependent on pH and temperature. This process followed quite well the pseudo-second-order release kinetics. Owing to the unique pH- and temperature-responsiveness together with their excellent biodegradability and biocompatibility, the CNFs-PEI aerogels were very promising as a new generation of controlled drug delivery carriers, offering simple and safe alternatives to the conventional systems from synthetic polymers.

  17. Chitosan-Poly (I:C)-PADRE Based Nanoparticles as Delivery Vehicles for Synthetic Peptide Vaccines. (United States)

    Correia-Pinto, Jorge F; Csaba, Noemi; Schiller, John T; Alonso, Maria J


    The safety and precision of peptide antigens has prompted the search for adjuvants capable of increasing the immune response against these intrinsically poorly immunogenic antigens. The integration of both immunostimulants and peptide antigens within nanometric delivery systems for their co-delivery to immune cells is a promising vaccination strategy. With this in mind, the potential synergistic effect of the immunostimulant poly (I:C) (pIC) and a T-Helper peptide (PADRE), integrated into a chitosan (CS) based nanostructure, was explored. The value of this nanostructured combination of materials was assessed for a peptide antigen (1338aa) derived from the HPV-16 L2 protein. These nanoparticles, produced by ionic gelation technique, exhibited a nanometric size (40 mV) and high pIC association efficiency (>96%). They also showed capacity for the association of both the 1338aa and PADRE peptides. The influence of the presence of pIC and PADRE in the nanocomposition, as well as that of the peptide presentation form (encapsulated versus surface adsorbed) on the antibody induction was evaluated in a preliminary in vivo study. The data obtained highlights the possibility to engineer nanoparticles through the rational combination of a number of adjuvant molecules together with the antigen.

  18. PNIPAAm-MAA nanoparticles as delivery vehicles for curcumin against MCF-7 breast cancer cells. (United States)

    Zeighamian, Vahideh; Darabi, Masoud; Akbarzadeh, Abolfazl; Rahmati-Yamchi, Mohammad; Zarghami, Nosratollah; Badrzadeh, Fariba; Salehi, Roya; Mirakabad, Fatemeh Sadat Tabatabaei; Taheri-Anganeh, Mortaza


    Breast cancer is the most frequently occurring cancer among women throughout the world. Natural compounds such as curcumin hold promise to treat a variety of cancers including breast cancer. However, curcumin's therapeutic application is limited, due to its rapid degradation and poor aqueous solubility. On the other hand, previous studies have stated that drug delivery using nanoparticles might improve the therapeutic response to anticancer drugs. Poly(N-isopropylacrylamide-co-methacrylic acid) (PNIPAAm-MAA) is one of the hydrogel copolymers utilized in the drug delivery system for cancer therapy. The aim of this study was to examine the cytotoxic potential of curcumin encapsulated within the NIPAAm-MAA nanoparticle, on the MCF-7 breast cancer cell line. In this work, polymeric nanoparticles were synthesized through the free radical mechanism, and curcumin was encapsulated into NIPAAm-MAA nanoparticles. Then, the cytotoxic effect of curcumin-loaded NIPAAm-MAA on the MCF-7 breast cancer cell line was measured by MTT assays. The evaluation of the results showed that curcumin-loaded NIPAAm-MAA has more cytotoxic effect on the MCF-7 cell line and efficiently inhibited the growth of the breast cancer cell population, compared with free curcumin. In conclusion, this study indicates that curcumin-loaded NIPAAm-MAA suppresses the growth of the MCF-7 cell line. Overall, it is concluded that encapsulating curcumin into the NIPAAm-MAA copolymer could open up new avenues for breast cancer treatment.

  19. Preparation and testing of quaternized chitosan nanoparticles as gene delivery vehicles. (United States)

    Li, Guang-Feng; Wang, Jing-Cheng; Feng, Xin-Min; Liu, Zhen-Dong; Jiang, Chao-Yong; Yang, Jian-Dong


    The aim of this study was to synthesize a chitosan (CS) derivative, a quaternary ammonium salt crystal called N-2-hydroxypropyl trimethyl ammonium chloride chitosan (HACC), and test a series of HACC and pEGFP-DNA complexes at different weight ratios for their efficiency of gene delivery into human cells. CS was modified with cationic etherifying agent to obtain the CS derivative. Fourier transform infrared spectra were recorded on KBr pellets with a spectrometer. (1)H nuclear magnetic resonance (NMR) spectra of HACC were obtained using a spectrometer. HACC was subsequently used to prepare HACC/DNA complexes at different weight ratios by coacervation method. The resulting particle size and surface charge were assessed by laser light scattering using a zeta potential analyzer. The HACC/DNA complex formation and DNA protection in the nanoparticle complex was investigated by gel mobility shift assay and DNase I protection assay, respectively. The cytotoxicity of HACC and HACC/DNA nanoparticles was evaluated by MTT assay using (mesenchymal stem cell) MSC lines. The nanoscale structure of the particles was obtained by transmission electron microscope (TEM). The FTIR spectrum of HACC showed the characteristic quaternary ammonium group absorption band at 1475 cm(-1), which indicated the presence of quaternary ammonium group. The successful synthesis of HACC was also confirmed by (1)H NMR spectrum. HACC showed good solubility in water and was electropositive. HACC efficiently packed and protected pEGFP-DNA at a weight ratio of 10. With increased weight ratios, the surface charge of the composite particle increased from negative to positive, the average particle size increased, and HACC nanoparticle had a higher carrying efficiency. The nanoparticles released DNA in two distinct phases, and 55 % was released within the first 20 h of solubilization. The nanoparticles under TEM showed circular or oval shapes. The particles exhibited no cytotoxicity against human cells. No

  20. Blood rheology in marine mammals

    Directory of Open Access Journals (Sweden)

    Michael Castellini


    Full Text Available The field of blood oxygen transport and delivery to tissues has been studied by comparative physiologists for many decades. Within this general area, the particular differences in oxygen delivery between marine and terrestrial mammals has focused mainly on oxygen supply differences and delivery to the tissues under low blood flow diving conditions. Yet, the study of the inherent flow properties of the blood itself (hemorheology is rarely discussed when addressing diving. However, hemorheology is important to the study of marine mammals because of the critical nature of the oxygen stores that are carried in the blood during diving periods. This review focuses on the essential elements of hemorheology, how they are defined and on fundamental rheological applications to marine mammals. While the comparative rationale used throughout the review is much broader than the particular problems associated with diving, the basic concepts focus on how changes in the flow properties of whole blood would be critical to oxygen delivery during diving. This review introduces the reader to most of the major rheological concepts that are relevant to the unique and unusual aspects of the diving physiology of marine mammals.

  1. RNAi-based therapeutic nanostrategy: IL-8 gene silencing in pancreatic cancer cells using gold nanorods delivery vehicles. (United States)

    Panwar, Nishtha; Yang, Chengbin; Yin, Feng; Yoon, Ho Sup; Chuan, Tjin Swee; Yong, Ken-Tye


    RNA interference (RNAi)-based gene silencing possesses great ability for therapeutic intervention in pancreatic cancer. Among various oncogene mutations, Interleukin-8 (IL-8) gene mutations are found to be overexpressed in many pancreatic cell lines. In this work, we demonstrate IL-8 gene silencing by employing an RNAi-based gene therapy approach and this is achieved by using gold nanorods (AuNRs) for efficient delivery of IL-8 small interfering RNA (siRNA) to the pancreatic cell lines of MiaPaCa-2 and Panc-1. Upon comparing to Panc-1 cells, we found that the dominant expression of the IL-8 gene in MiaPaCa-2 cells resulted in an aggressive behavior towards the processes of cell invasion and metastasis. We have hence investigated the suitability of using AuNRs as novel non-viral nanocarriers for the efficient uptake and delivery of IL-8 siRNA in realizing gene knockdown of both MiaPaCa-2 and Panc-1 cells. Flow cytometry and fluorescence imaging techniques have been applied to confirm transfection and release of IL-8 siRNA. The ratio of AuNRs and siRNA has been optimized and transfection efficiencies as high as 88.40 ± 2.14% have been achieved. Upon successful delivery of IL-8 siRNA into cancer cells, the effects of IL-8 gene knockdown are quantified in terms of gene expression, cell invasion, cell migration and cell apoptosis assays. Statistical comparative studies for both MiaPaCa-2 and Panc-1 cells are presented in this work. IL-8 gene silencing has been demonstrated with knockdown efficiencies of 81.02 ± 10.14% and 75.73 ± 6.41% in MiaPaCa-2 and Panc-1 cells, respectively. Our results are then compared with a commercial transfection reagent, Oligofectamine, serving as positive control. The gene knockdown results illustrate the potential role of AuNRs as non-viral gene delivery vehicles for RNAi-based targeted cancer therapy applications.

  2. An overview of drug delivery vehicles for cancer treatment: Nanocarriers and nanoparticles including photovoltaic nanoparticles. (United States)

    Chowdhury, Silvia; Yusof, Faridah; Salim, Wan Wardatul Amani Wan; Sulaiman, Nadzril; Faruck, Mohammad Omer


    Cancer is a complicated disease for which finding a cure presents challenges. In recent decades, new ways to treat cancer are being sought; one being nanomedicine, which manipulates nanoparticles to target a cancer and release drugs directly to the cancer cells. A number of cancer treatments based on nanomedicine are under way and mostly are in preclinical trials owing to challenges in administration, safety, and effectiveness. One alternative method for drug delivery is the use of photovoltaic nanoparticles, which has the potential to deliver drugs via light activation. The concepts are based on standard photovoltaic cell that holds opposite charges on its surfaces and releases drugs when charge intensity or polarity changes upon photo-stimulation such as from a laser source or sunlight. This review will cover some recent progress in cancer treatment using nanoparticles, including photovoltaic nanoparticles. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Use of Liposomes as Drug Delivery Vehicles for Treatment of Melanoma (United States)

    Tran, Melissa A.; Watts, Rebecca J.; Robertson, Gavin P.


    Melanoma is a progressive disease that claims many lives each year due to lack of therapeutics effective for the long-term treatment of patients. Currently, the best treatment option is early detection followed by surgical removal. Better melanoma therapies that are effectively delivered to tumors with minimal toxicity for patients are urgently needed. Nanotechnologies provide one approach to encapsulate therapeutic agents leading to improvements in circulation time, enhanced tumor uptake, avoidance of the reticulo-endothelial system, and minimization of toxicity. Liposomes in particular are a promising nanotechnology that can be used for more effective delivery of therapeutic agents to treat melanoma. Liposomes delivering chemotherapies, siRNA, asODNs, DNA, and radioactive particles are just some of the promising new nanotechnology based therapies under development for the treatment of melanoma that are discussed in this review. PMID:19493316

  4. Characterization and evaluation of nanostructured lipid carrier as a vehicle for oral delivery of etoposide. (United States)

    Zhang, Tiecheng; Chen, Jianian; Zhang, Yi; Shen, Qi; Pan, Weisan


    Nanostructured lipid carriers (NLCs) are a new generation of lipid nanoparticles, which have showed some advantages over traditional lipid nanoparticles, such as improved drug incorporation and release properties. The purpose of this study is to develop an optimized nanostructured lipid carrier formulation for etoposide (VP16), and to estimate the potential of NLCs as oral delivery system. VP16-NLCs were prepared by an emulsification and low-temperature solidification method. The average drug entrapment efficiency, particle size and zeta potential of VP16-NLCs, VP16-PEG40-St-modified NLCs (VP16-PEG40-NLCs) and VP16-DSPE-PE- modified NLCs (VP16-DSPE-NLCs) were 57.9-89.7%, 125.9-91.2 nm and -28.49 to -15.34 mV, respectively. The absorption of VP16-NLCs in the intestine was performed by the diffusion chamber. It was found that VP16-DSPE-NLCs with a smaller particle size made the drug transport easy from mucosal to serosal side. A pharmacokinetic study was conducted in rats. After oral administration of VP16 at a dose of 180 mg/kg in the form of either VP16-NLCs or suspension, the relative bioavailability of VP16-NLCs, VP16-PEG40-NLCs and VP16-DSPE-NLCs were enhanced about 1.8-, 3.0- and 3.5-fold, respectively, compared with VP16 suspension. Furthermore, VP16-DSPE-NLCs displayed the highest cytotoxicity against human epithelial-like lung carcinoma cells. The NLCs formulation remarkably improved the oral bioavailability of VP16 and demonstrated a promising perspective for oral delivery of VP16. Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.

  5. Preparation of cellular vehicles for delivery of gold nanorods to tumors (United States)

    Centi, S.; Borri, C.; Lai, S.; Tatini, F.; Colagrande, S.; Ratto, F.; Pini, R.


    Over recent years, gold nanorods (GNRs) have emerged as a promising material in biomedical optics and have been proposed as contrast agents for the photothermal therapy and the photoacoustic imaging of tumors. A pioneering approach to target tumors is the use of cellular vehicles, i.e. cells of the immune system that exhibit an innate tropism to tumors and that can be serve as Trojan horses. This strategy relies on cell types, such as tumor-associated macrophages or T cells, that are recruited by or naturally traffic to the microenvironment of tumors and that can be isolated from a patient and loaded with plasmonic particles in vitro. In this work, GNRs were synthesized and designed to combine high optical and photo-stability and the ability to accumulate into cells of the immuno system. Particles were silanized, PEGylated and conjugated with cationic moieties. Different cationic compounds were tested and the cell viability and uptake of the particles were studied on complementary cell types. The cytotoxicity test was based on a colorimetric WST-8 assay while the intracellular amount of gold and the optical absorbance of the cells were quantified by spectrophotometry. Moreover, we investigated the effect of GNRs on the cell migration and the production of cytokines in the presence of pro-inflammatory stimuli, which provide a functional overview on the feasibility of this approach to target.

  6. Human embryonic stem cell-derived endothelial cells as cellular delivery vehicles for treatment of metastatic breast cancer. (United States)

    Su, Weijun; Wang, Lina; Zhou, Manqian; Liu, Ze; Hu, Shijun; Tong, Lingling; Liu, Yanhua; Fan, Yan; Kong, Deling; Zheng, Yizhou; Han, Zhongchao; Wu, Joseph C; Xiang, Rong; Li, Zongjin


    Endothelial progenitor cells (EPCs) have shown tropism towards primary tumors or metastases and are thus potential vehicles for targeting tumor therapy. However, the source of adult EPCs is limited, which highlights the need for a consistent and renewable source of endothelial cells for clinical applications. Here, we investigated the potential of human embryonic stem cell-derived endothelial cells (hESC-ECs) as cellular delivery vehicles for therapy of metastatic breast cancer. In order to provide an initial assessment of the therapeutic potency of hESC-ECs, we treated human breast cancer MDA-MB-231 cells with hESC-EC conditioned medium (EC-CM) in vitro. The results showed that hESC-ECs could suppress the Wnt/β-catenin signaling pathway and thereby inhibit the proliferation and migration of MDA-MB-231 cells. To track and evaluate the possibility of hESC-EC-employed therapy, we employed the bioluminescence imaging (BLI) technology. To study the therapeutic potential of hESC-ECs, we established lung metastasis models by intravenous injection of MDA-MB-231 cells labeled with firefly luciferase (Fluc) and green fluorescent protein (GFP) to NOD/SCID mice. In mice with lung metastases, we injected hESC-ECs armed with herpes simplex virus truncated thymidine kinase (HSV-ttk) intravenously on days 11, 16, 21, and 26 after MDA-MB-231 cell injection. The NOD/SCID mice were subsequently treated with ganciclovir (GCV), and the growth status of tumor was monitored by Fluc imaging. We found that MDA-MB-231 tumors were significantly inhibited by intravenously injected hESC-ECs. The tumor-suppressive effects of the hESC-ECs, by inhibiting Wnt/β-catenin signaling pathway and inducing tumor cell death through bystander effect in human metastatic breast cancer model, provide previously unexplored therapeutic modalities for cancer treatment.

  7. pH sensitive silica nanotubes as rationally designed vehicles for NSAIDs delivery. (United States)

    Sousa, Célia T; Nunes, Cláudia; Proença, Mariana P; Leitão, Diana C; Lima, José L F C; Reis, Salette; Araújo, João P; Lúcio, Marlene


    A novel pH-sensitive drug delivery system based on functionalized silica nanotubes was developed for the incorporation of non-steroidal anti-inflammatory drugs (NSAIDs), aimed at a tailored drug release in acidic conditions characteristic of inflamed tissues. Silica nanotubes (SNTs) were synthesized by a nanoporous alumina template assisted sol-gel method. Inner surfaces were physically and chemically modified to improve both the functionalization and subsequent incorporation of the drug. Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS) and transmission electron microscopy (TEM) were used to characterize the designed nanocarriers and their functionalization. To achieve the highest degree of functionalization, three types of aminosilanes were tested and calcination conditions were optimized. APTES was shown to be the most effective aminosilane regarding the functionalization of the SNTs' inner surface and an adequate calcination temperature (220°C) was found to attain mechanical stability without compromising functionalization efficiency. Finally, the incorporation of naproxen into the nanotubes was accessed by fluorescence measurements and drug release studies were performed, revealing that the electrostatic linkage ensures effective release of the drug in the acidic pH typical of inflamed cells, while maintaining the SNT-drug conjugates stable at the typical bloodstream pH.

  8. Small-Angle Neutron Scattering and Spontaneous Formation of Unilamellar Vesicles: Potential Vehicles for Drug Delivery (United States)

    Katsaras, John


    Unilamellar vesicles (ULVs) are single-bilayer shells with radii commonly between 10 and 100 nm, and are widely used as model membranes, drug delivery systems, microreactors and substrates for a variety of enzymes and proteins. A common method of making ULVs is the extrusion of multilamellar vesicles (MLVs) through synthetic membranes of known pore size. These extruded ULVs are invariably unstable and in due time, revert back to MLVs. Over the years there have been reports of the spontaneous formation of stable ULVs in surfactant, lipid, and lipid/detergent mixtures. These ULVs have sometimes been shown to be monodisperse and their radii were found, almost without exception, to vary with concentration. We have carried-out small-angle neutron scattering (SANS) experiments on a biomimetic system composed of the phospholipids dimyristoyl and dihexanoyl phosphorylcholine (DMPC and DHPC, respectively). Doping DMPC/DHPC multilamellar vesicles with either the negatively charged lipid dimyristoyl phosphorylglycerol (DMPG, net charge -1) or the divalent cation, calcium (Ca2+) leads to the spontaneous formation of monodisperse unilamellar vesicles whose radii are concentration independent, in contrast to previous experimental observations.

  9. Bio-reducible polycations from ring-opening polymerization as potential gene delivery vehicles. (United States)

    Yu, Qing-Ying; Liu, Yan-Hong; Huang, Zheng; Zhang, Ji; Luan, Chao-Ran; Zhang, Qin-Fang; Yu, Xiao-Qi


    Synthetic polycations show great potential for the construction of ideal non-viral gene delivery systems. Several cationic polymers were synthesized by the epoxide ring-opening polymerization between diepoxide and various polyamines. Disulfide bonds were introduced to afford the polymers bio-reducibility, while the oxygen-rich structure might enhance the serum tolerance and biocompatibility. The polycations have much lower molecular weights than PEI 25 kDa, but still could well bind and condense DNA into nano-sized particles. DNA could be released from the polyplexes by addition of reductive DTT. Compared to PEI, the polycations have less cytotoxicity possibly due to their lower molecular weights and oxygen-rich structure. More significantly, these materials exhibit excellent serum tolerance than PEI, and up to 6 times higher transfection efficiency than PEI could be obtained in the presence of serum. The transfection mediated by was seldom affected even at a high concentration of serum. Much lower protein adsorption of polycations than PEI was proved by bovine serum albumin adsorption experiments. Flow cytometry also demonstrates their good serum resistance ability.

  10. Role of gold nanoparticles as drug delivery vehicles for chondroitin sulfate in the treatment of osteoarthritis. (United States)

    Dwivedi, Priyanka; Nayak, Vijayashree; Kowshik, Meenal


    Osteoarthritis is a disease which is characterized by joint pain, swelling and stiffness. Articular cartilage has limited self-repair capacity due to its avascular and aneural nature. In this work, we show the use of gold nanoparticles (AuNps) for enhancing the delivery of chondroitin sulfate (CS), a drug used in the treatment of osteoarthritis (OA). AuNps were synthesized and were characterized by transmission electron microscopy (TEM), ultraviolet-visible (UV-Vis) spectroscopy, Fourier transform infrared spectroscopy (FTIR), and X-Ray diffraction analysis. AuNps were combined with CS (AuNps-CS) and their effect on primary goat chondrocytes was studied using MTT assay, Hoechst staining, production of glycosaminoglycan and collagen. Cell viability studies by MTT revealed that AuNps-CS stimulate cell proliferation. A two-fold increase in GAG and collagen production was observed in presence of AuNps-CS combination as compared to native CS, indicating that this combination stimulates chondrocyte proliferation and enhances extracellular matrix production (ECM). Hence, this study exhibits the potential of AuNps as a carrier of CS for treatment of osteoarthritis.

  11. Engineering Virus Capsids Into Biomedical Delivery Vehicles: Structural Engineering Problems in Nanoscale. (United States)

    Bajaj, Saumya; Banerjee, Manidipa


    Virus capsids have evolved to protect the genome sequestered in their interior from harsh environmental conditions, and to deliver it safely and precisely to the host cell of choice. This characteristic makes them naturally perfect containers for delivering therapeutic molecules to specific locations. Development of an ideal virus-based nano-container for medical usage requires that the capsid be converted into a targetable protein cage which retains the original stability, flexibility and host cell penetrating properties of the native particles, without the associated immunogenicity, and is able to encapsulate large quantities of therapeutic or diagnostic material. In the last few years, several icosahedral, non-enveloped viruses, with a diameter of 25-90 nm-a size which conveniently falls within the 10-100 nm range desirable for biomedical nanoparticles-have been chemically or genetically engineered towards partial fulfilment of the above criteria. This review summarizes the approaches taken towards engineering viruses into biomedical delivery devices and discusses the challenges involved in achieving this goal.

  12. Bacterial Growth Kinetics under a Novel Flexible Methacrylate Dressing Serving as a Drug Delivery Vehicle for Antiseptics

    Directory of Open Access Journals (Sweden)

    Ojan Assadian


    Full Text Available A flexible methacrylate powder dressing (Altrazeal® transforms into a wound contour conforming matrix once in contact with wound exudate. We hypothesised that it may also serve as a drug delivery vehicle for antiseptics. The antimicrobial efficacy and influence on bacterial growth kinetics in combination with three antiseptics was investigated in an in vitro porcine wound model. Standardized in vitro wounds were contaminated with Staphylococcus aureus (MRSA; ATCC 33591 and divided into six groups: no dressing (negative control, methacrylate dressing alone, and combinations with application of 0.02% Polyhexamethylene Biguanide (PHMB, 0.4% PHMB, 0.1% PHMB + 0.1% betaine, 7.7 mg/mL Povidone-iodine (PVP-iodine, and 0.1% Octenidine-dihydrochloride (OCT + 2% phenoxyethanol. Bacterial load per gram tissue was measured over five days. The highest reduction was observed with PVP-iodine at 24 h to log10 1.43 cfu/g, followed by OCT at 48 h to log10 2.41 cfu/g. Whilst 0.02% PHMB resulted in a stable bacterial load over 120 h to log10 4.00 cfu/g over 120 h, 0.1% PHMB + 0.1% betaine inhibited growth during the first 48 h, with slightly increasing bacterial numbers up to log10 5.38 cfu/g at 120 h. These results indicate that this flexible methacrylate dressing can be loaded with various antiseptics serving as drug delivery system. Depending on the selected combination, an individually shaped and controlled antibacterial effect may be achieved using the same type of wound dressing.

  13. Bacterial Growth Kinetics under a Novel Flexible Methacrylate Dressing Serving as a Drug Delivery Vehicle for Antiseptics (United States)

    Forstner, Christina; Leitgeb, Johannes; Schuster, Rupert; Dosch, Verena; Kramer, Axel; Cutting, Keith F.; Leaper, David J.; Assadian, Ojan


    A flexible methacrylate powder dressing (Altrazeal®) transforms into a wound contour conforming matrix once in contact with wound exudate. We hypothesised that it may also serve as a drug delivery vehicle for antiseptics. The antimicrobial efficacy and influence on bacterial growth kinetics in combination with three antiseptics was investigated in an in vitro porcine wound model. Standardized in vitro wounds were contaminated with Staphylococcus aureus (MRSA; ATCC 33591) and divided into six groups: no dressing (negative control), methacrylate dressing alone, and combinations with application of 0.02% Polyhexamethylene Biguanide (PHMB), 0.4% PHMB, 0.1% PHMB + 0.1% betaine, 7.7 mg/mL Povidone-iodine (PVP-iodine), and 0.1% Octenidine-dihydrochloride (OCT) + 2% phenoxyethanol. Bacterial load per gram tissue was measured over five days. The highest reduction was observed with PVP-iodine at 24 h to log10 1.43 cfu/g, followed by OCT at 48 h to log10 2.41 cfu/g. Whilst 0.02% PHMB resulted in a stable bacterial load over 120 h to log10 4.00 cfu/g over 120 h, 0.1% PHMB + 0.1% betaine inhibited growth during the first 48 h, with slightly increasing bacterial numbers up to log10 5.38 cfu/g at 120 h. These results indicate that this flexible methacrylate dressing can be loaded with various antiseptics serving as drug delivery system. Depending on the selected combination, an individually shaped and controlled antibacterial effect may be achieved using the same type of wound dressing. PMID:23698780

  14. Entrapment of ketorolac tromethamine in polymeric vehicle for controlled drug delivery

    Directory of Open Access Journals (Sweden)

    Paliwal S


    Full Text Available The most common method for applying a drug in to the eye is to formulate the drug in the form of an eye drop, but this method is not considered ideal for ocular delivery of drug because of poor bioavailability arising from precorneal loss processes, this loss of drug from the precorneal area is a net effect of drainage, tear secretion and noncorneal absorption. Following the above lead we tried to improve the ocular bioavailability by increasing the corneal contact time and the feasible way was to formulate a drug with mucoadhesive/viscosity imparting agents. The adhesive strength of various polymers on corneal surface was studied with the help of self modified Franz diffusion cell and freshly excised goat/bovine cornea. The polymers hydroxypropylmethylcellulose, carboxymethylcellulose sodium, Eudragit type E/RL/RS, Carbopol ETD 2020 and Carbopol 934 National Formulary were formulated with drug, ketorolac tromethamine. The adhesive strength of polymers on corneal surface and permeation characteristics of drug through cornea were investigated by using above said formulations. Eudragit type E/RL/RS did not show any improvement in mucoadhesion, but the formulations containing Carbopol ETD 2020 and Carbopol 934 national formulary showed good mucoadhesion on corneal surface in the concentration as low as 0.75%. The mucoadhesive strength was also evaluated using the combination of Carbopol acrylates/C 10-30 alkylacrylate with allylpentaerithrital and preservative benzalkonium chloride, which also resulted in good mucoadhesion with improved corneal permeation. Observations made in this study indicate the potentiality of the ophthalmic formulations containing mucoadhesive/viscosity imparting agents.

  15. RGD-conjugated albumin nanoparticles as a novel delivery vehicle in pancreatic cancer therapy. (United States)

    Ji, Shunrong; Xu, Jin; Zhang, Bo; Yao, Wantong; Xu, Wenyan; Wu, Wenzhe; Xu, Yongfeng; Wang, Hao; Ni, Quanxing; Hou, Huimin; Yu, Xianjun


    Integrin αvβ3 receptor is expressed on several types of cancer cells, including pancreatic cancer cells, and plays an important role in tumor growth and metastasis. The ability to target the integrin αvβ3 receptor on cancer cells increases the efficacy of targeted therapy and reduces the side effects. The aim of this study is to develop a novel arginine-glycine-aspartic acid (RGD) peptide -conjugated albumin nanoparticle to enhance the intracellular uptake of anticancer drug into the pancreatic cancer cells through receptor-mediated endocytosis. In the cellular uptake studies, the fluorescent signal of RGD-conjugated BSANPs in BxPC3 cells was higher than that of BSANPs without RGD conjugation as determined by fluorescence spectrophotometer. We also found that BSANPs bound to BxPC3 cells in a time- and concentration-dependent manner. The uptake of RGD-conjugated BSANPs by pancreatic cancer cells was inhibited by an excess amount of free RGD peptide, indicating that the binding and/or uptake were mediated by the αvβ3 receptor. Furthermore, the nanoparticles were found to be located close to the nuclei by using laser scanning confocal microscopy. Besides, no significant in vitro cytotoxicity was observed as measured with MTT assay. Both in vitro and in vivo antitumor efficacy was improved by targeting gemcitabine-loaded nanoparticles to BxPC-3 cells using RGD peptides. Therefore, the RGD-conjugated BSANPs hold great potential as an effective drug delivery system to deliver therapeutic agents to pancreatic cancer.

  16. Evidence of nose-to-brain delivery of nanoemulsions: cargoes but not vehicles. (United States)

    Ahmad, Ejaj; Feng, Yunhai; Qi, Jianping; Fan, Wufa; Ma, Yuhua; He, Haisheng; Xia, Fei; Dong, Xiaochun; Zhao, Weili; Lu, Yi; Wu, Wei


    The nose-to-brain pathway has been proven to be a shortcut for direct drug delivery to the brain. However, whether and to what extent nanoparticles can be delivered through this passage is still awaiting validation with evidence. In this study, nose-to-brain transportation of nanoparticles is tracked via fluorescence bioimaging strategies using nanoemulsions (NEs) as model carriers. Identification of NEs in biological tissues is based on the on → off signal switching of a new type of environment-responsive embedded dyes, P2 and P4, and two conventional probes, DiR and coumarin-6 (C6), are embedded to represent the cargoes. Evidence for the translocation of NEs was collected either via live imaging or ex vivo histological examination in rats after nasal administration. Results suggest that NEs with a particle size of about 100 nm, either naked or coated with chitosan, have longer retention duration in nostrils and slower mucociliary clearance than larger ones. P2 signals, representing integral NEs, can be found in mucosa and trigeminal nerves for all size groups, whereas only weak P2 signals are detected in the olfactory bulb for chitosan-coated NEs of 100 nm. Confocal microscopy further confirms the translocation of integral 100 nm NEs in nasal mucosa and along the trigeminal nerve in decremental intensity. Weak signals of the P4 probe, also representing integral NEs, can be detected in the olfactory bulb but few in the brain. NEs as large as 900 nm cannot be transported to the olfactory bulb. However, the DiR or C6 signals that represent the cargoes can be found in significant amounts along the nose-to-brain pathway and finally reach the brain. Evidence shows that integral NEs can be delivered to the olfactory bulb, but few to the brain, whereas the cargoes can be released and permeated into the brain in greater amounts.

  17. Chitosan-genipin nanohydrogel as a vehicle for sustained delivery of alpha-1 antitrypsin. (United States)

    Ghasemi, Ahmad; Mohtashami, Mahnaz; Sheijani, Samaneh Sotoudeh; Aliakbari, Kamelya


    Alpha-1antitrypsin (A1AT) deficiency, an inherited disorder, has been shown to be the cause of lung diseases such as emphysema and chronic obstructive pulmonary disease. One of the treatment strategies to provide appropriate and adequate concentrations of A1AT in the lungsis the application of nanoparticles (NPs) in pulmonary drug delivery. In the current study, biocompatible nanohydrogels were prepared using chemically cross-linked chitosan with ginepin, a natural cross linker reagent, and used as a carrier to deposit A1AT into the lung tissue. Colloidal and monodispersed NPs were synthesized through reverse microemulsion. Nanohydrogels were characterized with TEM, LLS, FTIR, ZTEA potential, UV spectrum, and swelling test. Encapsulation efficacy was determined at different concentrations of A1AT using Bradford assay. Effect of processing variables such as pH, loading efficiency, and release media components on drug release profile was determined in simulated lung fluids. To evaluate the inhibitory activity of the A1AT after release from NPs, trypsin inhibitory capacity assay was carried out. Results from FTIR and UV spectrum confirmed the development of chitosan cross linkage. Spherical chitosan-genipin NPs were sized from 30-100 nm. NPs exhibited the ability to release 49% of the drug within 12-dayperiodatpH 7. However, there were variations with the drug release profile due to pH variations and loading efficacy. Drug release was higher in pseudo alveolar fluid in comparison with saline solution. These data indicate that application of chitosan nanohydrogels can be a useful tool for sustained release of A1AT in the lung tissue.

  18. Disc-shaped polyoxyethylene glycol glycerides gel nanoparticles as novel protein delivery vehicles. (United States)

    Codoni, Doroty; Cowan, Jonathan; Bradley, Jenna; McAuley, William J; O'Connell, Maria A; Qi, Sheng


    Disc-shaped nanoparticles with high aspect ratios have been reported to show preferential cellular uptake in vitro by mammalian cells. However, engineering and producing such disc-shaped nanoparticles are often complex. This study reports for the first time the use of a single, approved pharmaceutical excipient to prepare stable disc-shaped nanoparticles with a high aspect ratio via a simple, organic solvent free process. These disc-shaped nanoparticles were formed by fragmentation of stearoyl macrogol-32 glycerides (Gelucire 50/13) hydrogels. The nanoparticles showed good physical stability as a result of their outer coating of polyethylene glycol (PEG) that is a part of Gelucire composition. Using lysozyme as a model hydrophilic protein, these nanoparticles demonstrated a good loading capacity for hydrophilic macromolecules, mainly via surface adsorption. As a result of the higher hydrophobicity of the core of the nano-discs, the loading efficiency of hydrophobic model components, such as Coumarin-6, was significantly increased in comparison to the model hydrophilic compound. These Gelucire nano-discs exhibited no cytotoxicity at the tested level of 600μg/ml for Caco-2 cells. Rapid in vitro cellular uptake of the disc-shaped nanoparticles by Caco-2 cells was observed. This rapid internalisation was attributed to the high aspect ratio of the disc-shape nanoparticles which provides a high contact surface area between the particles and cells and may lower the strain energy required for membrane deformation during uptake. The results of this study demonstrate the promising potential of Gelucire nano-discs as effective nanocarriers for drug delivery and which can be manufactured using a simple solvent-free process.

  19. Preference for gel over suppository as delivery vehicle for a rectal microbicide: Results of a randomized, crossover acceptability trial among men who have sex with men (United States)

    Carballo-Diéguez, A.; Dolezal, C.; Bauermeister, J.A.; O’Brien, B.; Ventuneac, A.; Mayer, K.


    Objective To assess whether men who have sex with men (MSM) prefer a gel or a suppository as a delivery vehicle for a rectal microbicide. Methods 77 HIV-negative MSM with recent history of inconsistent condom use during receptive anal intercourse (RAI) who acknowledged being at risk of contracting HIV were enrolled in a randomized, crossover acceptability trial. They compared 35 ml of placebo gel with 8 g placebo rectal suppositories used in up to three RAI occasions each. Results Participants preferred the gel over the suppository (75% vs. 25%, p suppository as a potential microbicide vehicle. PMID:19028952

  20. Introducing the MCHF/OVRP/SDMP: Multicapacitated/Heterogeneous Fleet/Open Vehicle Routing Problems with Split Deliveries and Multiproducts

    Directory of Open Access Journals (Sweden)

    Duygu Yilmaz Eroglu


    Full Text Available In this paper, we analyze a real-world OVRP problem for a production company. Considering real-world constrains, we classify our problem as multicapacitated/heterogeneous fleet/open vehicle routing problem with split deliveries and multiproduct (MCHF/OVRP/SDMP which is a novel classification of an OVRP. We have developed a mixed integer programming (MIP model for the problem and generated test problems in different size (10–90 customers considering real-world parameters. Although MIP is able to find optimal solutions of small size (10 customers problems, when the number of customers increases, the problem gets harder to solve, and thus MIP could not find optimal solutions for problems that contain more than 10 customers. Moreover, MIP fails to find any feasible solution of large-scale problems (50–90 customers within time limits (7200 seconds. Therefore, we have developed a genetic algorithm (GA based solution approach for large-scale problems. The experimental results show that the GA based approach reaches successful solutions with 9.66% gap in 392.8 s on average instead of 7200 s for the problems that contain 10–50 customers. For large-scale problems (50–90 customers, GA reaches feasible solutions of problems within time limits. In conclusion, for the real-world applications, GA is preferable rather than MIP to reach feasible solutions in short time periods.

  1. Introducing the MCHF/OVRP/SDMP: multicapacitated/heterogeneous fleet/open vehicle routing problems with split deliveries and multiproducts. (United States)

    Eroglu, Duygu Yilmaz; Gencosman, Burcu Caglar; Cavdur, Fatih; Ozmutlu, H Cenk


    In this paper, we analyze a real-world OVRP problem for a production company. Considering real-world constrains, we classify our problem as multicapacitated/heterogeneous fleet/open vehicle routing problem with split deliveries and multiproduct (MCHF/OVRP/SDMP) which is a novel classification of an OVRP. We have developed a mixed integer programming (MIP) model for the problem and generated test problems in different size (10-90 customers) considering real-world parameters. Although MIP is able to find optimal solutions of small size (10 customers) problems, when the number of customers increases, the problem gets harder to solve, and thus MIP could not find optimal solutions for problems that contain more than 10 customers. Moreover, MIP fails to find any feasible solution of large-scale problems (50-90 customers) within time limits (7200 seconds). Therefore, we have developed a genetic algorithm (GA) based solution approach for large-scale problems. The experimental results show that the GA based approach reaches successful solutions with 9.66% gap in 392.8 s on average instead of 7200 s for the problems that contain 10-50 customers. For large-scale problems (50-90 customers), GA reaches feasible solutions of problems within time limits. In conclusion, for the real-world applications, GA is preferable rather than MIP to reach feasible solutions in short time periods.

  2. Integrated Testing, Simulation and Analysis of Electric Drive Options for Medium-Duty Parcel Delivery Vehicles: Preprint

    Energy Technology Data Exchange (ETDEWEB)

    Ramroth, L. A.; Gonder, J.; Brooker, A.


    The National Renewable Energy Laboratory verified diesel-conventional and diesel-hybrid parcel delivery vehicle models to evaluate petroleum reduction and cost implications of plug-in hybrid gasoline and diesel variants. These variants are run on a field-data-derived design matrix to analyze the effects of drive cycle, distance, battery replacements, battery capacity, and motor power on fuel consumption and lifetime cost. Two cost scenarios using fuel prices corresponding to forecasted highs for 2011 and 2030 and battery costs per kilowatt-hour representing current and long-term targets compare plug-in hybrid lifetime costs with diesel conventional lifetime costs. Under a future cost scenario of $100/kWh battery energy and $5/gal fuel, plug-in hybrids are cost effective. Assuming a current cost of $700/kWh and $3/gal fuel, they rarely recoup the additional motor and battery cost. The results highlight the importance of understanding the application's drive cycle, daily driving distance, and kinetic intensity. For instances in the current-cost scenario where the additional plug-in hybrid cost is regained in fuel savings, the combination of kinetic intensity and daily distance travelled does not coincide with the usage patterns observed in the field data. If the usage patterns were adjusted, the hybrids could become cost effective.

  3. Biodirected synthesis of Miconazole-conjugated bacterial silver nanoparticles and their application as antifungal agents and drug delivery vehicles. (United States)

    Kumar, C Ganesh; Poornachandra, Y


    The recent strategy to improve the efficacy of drugs is to combine them with metal nanoparticles for the control of microbial infections. Considering this fact, we developed a low cost and eco-friendly method for silver nanoparticles synthesis using the cell free supernatant of Delftia sp. strain KCM-006 and their application as antifungal agents and as a drug carrier. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) analysis revealed the formation of spherical and monodispersed silver nanoparticles with an average size of 9.8 nm. The synthesized nanoparticles were found to be photoluminescent, highly stable and crystalline in nature having a zeta potential of -31 mV. The silver nanoparticles exhibited very good antifungal activity against various pathogenic Candida strains. Furthermore, the efficacy of nanoparticles was increased by conjugating the antifungal drug Miconazole to silver nanoparticles which exhibited significant fungicidal activity, inhibition of ergosterol biosynthesis and biofilm inhibition by increasing ROS levels. In addition, the cell viability and immunocytochemistry analysis against different normal cell lines including Chinese hamster ovary cells (CHO), human lung cell line (MRC5) and human vascular endothelial cells (HUVEC) demonstrated that these nanoparticles were non-toxic up to a concentration of 20 μM. In conclusion, these results suggest that the synthesized nanoparticles find application as both antifungal agents and drug delivery vehicles. This is a first report on the preparation of silver nanoparticles using culture supernatant from Delftia sp. and also on the conjugation of Miconazole, an antifungal drug, to the bacterial silver nanoparticles.

  4. Liposomal systems as viable drug delivery technology for skin cancer sites with an outlook on lipid-based delivery vehicles and diagnostic imaging inputs for skin conditions'. (United States)

    Akhtar, Naseem; Khan, Riaz A


    Skin cancer is among one of the most common human malignancies wide-spread world-over with mortality statistics rising continuously at an alarming rate. The increasing frequency of these malignancies has marked the need for adopting effective treatment plan coupled with better and site-specific delivery options for the desired therapeutic agent's availability at the affected site. The concurrent delivery approaches to cancerous tissues are under constant challenge and, as a result, are evolving and gaining advancements in terms of delivery modes, therapeutic agents and site-specificity of the therapeutics delivery. The lipid-based liposomal drug delivery is an attractive and emerging option, and which is meticulously shaping up beyond a threshold level to a promising, and viable route for the effective delivery of therapeutic agents and other required injuctions to the skin cancer. An update on liposomal delivery of chemotherapeutic agents, natural-origin compounds, photosensitizer, and DNA repair enzymes as well as other desirable and typical delivery modes employed in drug delivery and in the treatment of skin cancers is discussed in details. Moreover, liposomal delivery of nucleic acid-based therapeutics, i.e., small interfering RNA (siRNA), mRNA therapy, and RGD-linked liposomes are among the other promising novel technology under constant development. The current clinical applicability, viable clinical plans, future prospects including transport feasibility of delivery vesicles and imaging techniques in conjunction with the therapeutic agents is also discussed. The ongoing innovations in liposomal drug delivery technology for skin cancers hold promise for further development of the methodology for better, more effective and site-specific delivery as part of the better treatment plan by ensuring faster drug transport, better and full payload delivery with enough and required concentration of the dose. Copyright © 2016 Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Dong X


    Full Text Available Xia Dong, Lanxia Liu, Dunwan Zhu, Hailing Zhang, Xigang Leng Laboratory of Bioengineering, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin Key Laboratory of Biomedical Materials, Tianjin, People’s Republic of China Abstract: Carbon nanotube (CNT-based drug delivery vehicles might find great potential in cancer therapy via the combination of chemotherapy with photothermal therapy due to the strong optical absorbance of CNTs in the near-infrared region. However, the application of CNTs in cancer therapy was considerably constrained by their lack of solubility in aqueous medium, as well as the cytotoxicity caused by their hydrophobic surface. Intracellular delivery efficiency is another factor determining the application potential of CNTs in cancer therapy. In the present study, low-molecular-weight chitosan conjugated with transactivator of transcription (TAT peptide was used for noncovalent functionalization of multiwalled carbon nanotubes (MWCNTs, aiming at providing a more efficient drug delivery vehicle for cancer therapy. The TAT–chitosan-conjugated MWCNTs (MWCNTs-TC were further investigated for their water solubility, cytotoxicity, cell-penetrating capability, and accumulation in tumor. It was found that MWCNTs-TC were essentially nontoxic with satisfying water solubility, and they were more efficient in terms of cancer-targeted intracellular transport both in vitro and in vivo as compared with chitosan-modified MWCNTs (MWCNTs-CS, suggesting the great application potential of MWCNTs-TC in cancer therapy. Keywords: carbon nanotube, TAT, chitosan, drug delivery

  6. Rheology in Pharmaceutical Sciences

    DEFF Research Database (Denmark)

    Aho, Johanna; Hvidt, Søren; Baldursdottir, Stefania


    Rheology is the science of flow and deformation of matter. Particularly gels and non-Newtonian fluids, which exhibit complex flow behavior, are frequently encountered in pharmaceutical engineering and manufacturing, or when dealing with various in vivo fluids. Therefore understanding rheology...... is important, and the ability to use rheological characterization tools is of great importance for any pharmaceutical scientist involved in the field. Flow can be generated by shear or extensional deformations, or a combination of both. This chapter introduces the basics of both shear and extensional rheology...

  7. Role of different vehicles in carotenoids delivery and their influence on cell viability, cell cycle progression, and induction of apoptosis in HeLa cells. (United States)

    Sowmya, Poorigali Raghavendra-Rao; Arathi, Bangalore Prabhashankar; Vijay, Kariyappa; Baskaran, Vallikannan; Lakshminarayana, Rangaswamy


    The objective of the present study was to determine the role of different vehicles in carotenoids delivery and their influence on cell viability, cell cycle progression and induction of apoptosis in HeLa cells. Cells (5 × 10(3)) were treated with different concentrations (25-100 µM) of β-carotene (BC) or lutein (L) or astaxanthin (AST) dissolved in 0.5% of tetrahydrofuran (THF), dimethylsulfoxide (DMSO), and fetal bovine serum (FBS), respectively. The effect of delivery vehicle on carotenoids uptake, cytotoxicity, oxidative status, cell cycle distribution, and apoptosis was examined after 48 h of incubation. The results shown that, cell viability reduced significantly in a dose- and time-dependent manner irrespective of carotenoid delivered in vehicles. Cellular uptake of BC delivered in THF was higher by 49.1, 29.7% and L delivered through THF was higher by 41.7 and 37.5% than DMSO and FBS, respectively. While, AST delivered through DMSO was higher by 36.1 and 43.7% than the THF and FBS, respectively. In case of cells treated either with BC or L delivered through THF and AST in DMSO decreased the glutathione and increased the malondialdehyde levels. The net increase in the G 2/M phase percentage of cell cycle progression was observed in carotenoid-treated cells. The % induction of apoptosis by BC or L delivered with THF and AST in DMSO was higher than other treated groups. In conclusion, choice of suitable vehicle for specific carotenoids delivery is essential that in turn may influence on cell proliferation and cell-based assays.

  8. Feedback Drug Delivery Vehicles (United States)


    protect it from metabolism while inside the nanogels. Morphine and naloxone blood concentrations are also detected independently shown in Figure 7...presence of naloxone nanogel does not effect the metabolism of morphine . Naloxone concentration was higher than injection with free naloxone and... morphine causes hypoventilation, an inadequate 1. REPORT DATE (DD-MM-YYYY) 4. TITLE AND SUBTITLE 28-06-2012 13. SUPPLEMENTARY NOTES The views

  9. Rheology and structure of thermoreversible hydrogels (United States)

    Jiang, Jun


    Highly concentrated solutions of non-ionic amphiphilic triblock copolymer poly(ethylene oxide)99-poly(propylene oxide)67-poly(ethylene oxide)99 (Pluronic F127) are widely used in numerous biomedical applications, such as drug delivery vehicles, and surfactants for emulsification of food and personal care products. The Pluronic copolymers are popular for these applications, since their gelation properties are thermoreversible and easily controlled by varying the concentration. They are liquid below room temperature and gel at body temperature. Hence they are great injectable biomaterials for tissue engineering and implantation. In this dissertation, thermal gelation and structure of high concentration triblock copolymer Pluronic F127-clay (Cloisite Na+ and Lucentite SWN) aqueous solutions were characterized by rheological measurements, differential scanning calorimetry (DSC) and small angle X-ray/neutron scattering. Small angle neutron scattering (SANS), under shear using a Couette cell in radial and tangential scattering geometry, was performed to examine the structural evolution of the polymeric micellar macro-lattice formed by concentrated aqueous solutions of triblock copolymer-Pluronic F127, as a function of the shear rate. The micellar gel showed a shear thinning, i.e., a reduction of the resistance to shear, by forming a layered stacking of two-dimensional hexagonally close packed (HCP) polymer micelles. A theoretical model was developed to calculate 2D SANS scattering patterns that can be compared with the experimental data. In order to improve the mechanical properties of the gel, while still maintaining the thermo-reversibility, we synthesized multiblock structures, where the F127 construct would be repeated several times. In this manner, physical interconnections between the micelles could occur as the multiblock copolymers formed interlocking loops and tails, thereby greatly increasing the mechanical strength of the gels. The rheological and structural

  10. Rheology of organoclay suspension

    CSIR Research Space (South Africa)

    Hato, MJ


    Full Text Available -1 Colloid & Polymer Science Volume 289, Number 10, 1119-1125, DOI: 10.1007/s00396-011-2438-4 Rheology of organoclay suspension Mpitloane Joseph Hato, Ke Zhang, Suprakas Sinha Ray and Hyoung Jin Choi Abstract We have studied the rheological...

  11. Penerapan Algoritma Genetika Untuk Penyelesaian Vehicle Routing Problem With Delivery And Pick-Up (VRP-DP)


    Simanullang, Herlin


    Vehicle Routing Problem (VRP) is a problem of combinatorial optimization complexeses that has essential role in management distribution system which is aimed to minimize the needed cost, the cost is determined in relationship with the distance of route which is taken by the distribution vehicle. The characteristic from VRP is the use of vehicle in certain capacity and its activity is centralized in one depot to serve the customer on certain locations with certain known demand. ...

  12. Rheology and deep tectonics

    Directory of Open Access Journals (Sweden)

    G. Ranalli


    Full Text Available The distribution of the rheological properties of the lithosphere in space, and their variations in time, have a profound effect on the resulting tectonic deformation. A classical way of estimating these properties makes use of rheological profiles (strength envelopes. Although rheological profiles are based on assumptions and approximations which limit their resolving power, they are an efficient first-order tool for the study of lithosphere rheology, and their application clarifies the dynamics of tectonic processes. Two examples of the interaction of rheology and tectonics are discussed, namely, the post-orogenic relaxation of Moho topography (which is an additional factor to be considered in tectonic inversion, and the strength control on the level of necking in extension (which may lead to apparent local isostasy at passive continental margins and in sedimentary basins.

  13. An Experimental Study on the Dynamic Characteristics of Vehicle Semi-active Seat Suspension with Magneto-rheological Damper%汽车磁流变半主动座椅悬架动态特性的试验研究

    Institute of Scientific and Technical Information of China (English)



    For further improving vehicle ride comfort,a magneto-rheological damper for vehicle semi-active seat suspension is developed with its damping characteristic test conducted. After analyzing its force bearing condi-tion, a dynamics model for vehicle semi-active seat suspension is built, a corresponding skyhook control strategy is devised, and a simulation is performed on the skyhook control of seat under both random and sinusoidal excitation inputs. Meanwhile a physical prototype of semi-active seat suspension with magneto-rheological damper and its test bench system are developed with corresponding bench test carried out. The results indicate that the results of simu-lation basically well agree with test data and the magneto-rheological damper developed has a good damping control-lability. Compared to original passive seat suspension, the dynamic performances of vehicle semi-active seat with magneto-rheological damper are improved by some 30% with a significant effect of vibration attenuation.%为进一步提高汽车的乘坐舒适性,研发了一种汽车座椅半主动悬架用磁流变减振器,并对其进行阻尼特性试验,通过分析其受力情况,建立了汽车半主动座椅悬架动力学模型,设计了用于座椅磁流变半主动悬架的天棚控制策略,并在随机和正弦激励输入下进行了座椅天棚控制仿真计算,试制了磁流变半主动座椅物理样机及试验台架系统,开展了磁流变半主动座椅悬架的台架试验研究。结果表明,理论仿真和试验结果基本吻合,磁流变减振器阻尼可控性好;相对于被动座椅悬架,采用磁流变半主动座椅悬架后,座椅动态性能改善了30%左右,磁流变半主动座椅悬架减振效果显著。

  14. 需求可拆分的开放式车辆路径问题研究%Research on Split Delivery Open Vehicle Routing Problem

    Institute of Scientific and Technical Information of China (English)

    李三彬; 柴玉梅; 王黎明


    The traditional Open Vehicle Routing Problem(OVRP) assumes that the demand of the clients can not be split and the type of vehicles is the same, but in the practical logistics distribution, the type of vehicles is not exactly the same, sometimes the transportation cost can be reduced by splitting the demand of clients to make the best of the loading capacity of vehicles.This paper proposes the Split Delivery Open Vehicle Routing Problem with Heterogeneous Vehicles(SDOVRPHV), presents mathematic model of the integer programming of the problem, solves it with Tabu search algorithm and improves the generation of the initial solution and neighborhood structure in the algorithm.By experiments, the validity of the model is validated, and the results are compared with the traditional OVRP which indicates that the algorithm can reduce effectively the transportation cost.%传统的开放式车辆路径问题假设客户的需求不可拆分、车辆类型相同,但在实际的物流配送中,车辆类型不完全相同,对需求的拆分能充分利用车辆的装载能力,降低运输成本.为此,提出需求可拆分的不同种车辆的开放式车辆路径问题,给出整数规划的数学模型,利用禁忌搜索算法对该问题求解,改进算法中初始解和邻域结构的产生过程.通过实验验证模型的有效性,并将结果与传统的开放式车辆路径问题进行比较,表明该算法可有效减少运输成本.

  15. Improving Transportation Services for the University of the Thai Chamber of Commerce: A Case Study on Solving the Mixed-Fleet Vehicle Routing Problem with Split Deliveries (United States)

    Suthikarnnarunai, N.; Olinick, E.


    We present a case study on the application of techniques for solving the Vehicle Routing Problem (VRP) to improve the transportation service provided by the University of The Thai Chamber of Commerce to its staff. The problem is modeled as VRP with time windows, split deliveries, and a mixed fleet. An exact algorithm and a heuristic solution procedure are developed to solve the problem and implemented in the AMPL modeling language and CPLEX Integer Programming solver. Empirical results indicate that the heuristic can find relatively good solutions in a small fraction of the time required by the exact method. We also perform sensitivity analysis and find that a savings in outsourcing cost can be achieved with a small increase in vehicle capacity.

  16. Self-assembled PEG-b-PDPA-b-PGEM copolymer nanoparticles as protein antigen delivery vehicles to dendritic cells: preparation, characterization and cellular uptake (United States)

    Li, Pan; Zhou, Junhui; Huang, Pingsheng; Zhang, Chuangnian; Wang, Weiwei; Li, Chen; Kong, Deling


    Antigen uptake by dendritic cells (DCs) is a key step for initiating antigen-specific T cell immunity. In the present study, novel synthetic polymeric nanoparticles were prepared as antigen delivery vehicles to improve the antigen uptake by DCs. Well-defined cationic and acid-responsive copolymers, monomethoxy poly(ethylene glycol)-block-poly(2-(diisopropyl amino) ethyl methacrylate)-block-poly(2-(guanidyl) ethyl methacrylate) (mPEG-b-PDPA-b-PGEM, PEDG) were synthesized by reversible addition-fragmentation chain transfer polymerization of 2-(diisopropylamino)ethyl methacrylate) and N-(tert-butoxycarbonyl) amino ethyl methacrylate monomers, followed by deprotection of tert-butyl protective groups and guanidinylation of obtained primary amines. 1H NMR, 13C NMR and GPC results indicated the successful synthesis of well-defined PEDG copolymers. PEDG copolymers could self-assemble into nanoparticles in aqueous solution, which were of cationic surface charges and showed acid-triggered disassembly contributed by PGEM and PDPA moieties, respectively. Significantly, PEDG nanoparticles could effectively condense with negatively charged model antigen ovalbumin (OVA) to form OVA/PEDG nanoparticle formulations with no influence on its secondary and tertiary structures demonstrating by far-UV circular dichroism and UV–vis spectra. In vitro antigen cellular uptake by bone marrow DCs (BMDCs) indicated using PEDG nanoparticles as antigen delivery vehicles could significantly improve the antigen uptake efficiency of OVA compared with free OVA or the commercialized Alum adjuvant. Moreover, as the surface cationic charges of OVA/PEDG nanoparticle formulations reduced, the uptake efficiency decreased correspondingly. Collectively, our work suggests that guanidinylated, cationic and acid-responsive PEDG nanoparticles represent a new kind of promising antigen delivery vehicle to DCs and hold great potential to serve as immunoadjuvants in the development of vaccines. PMID:28149525

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

    Directory of Open Access Journals (Sweden)

    Sebastian O Wendel

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

  18. Cell Based Drug Delivery: Micrococcus luteus Loaded Neutrophils as Chlorhexidine Delivery Vehicles in a Mouse Model of Liver Abscesses in Cattle. (United States)

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


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

  19. Clustering algorithm for split delivery vehicle routing problem%需求可拆分车辆路径问题的聚类求解算法

    Institute of Scientific and Technical Information of China (English)

    刘旺盛; 杨帆; 李茂青; 陈培芝


    In the traditional vehicle routing problems, customer demands are usually assumed that they can not be split. That is to say, a customer can only be severed by a vehicle. In fact, split delivery requires fewer vehicles, which reduces transportation costs. This paper analyzes the solution's characteristics of split delivery vehicle routing problem, and also proves the situations that customers' demands can not be split. A clustering algorithm meeting the solution's characteristics is designed to solve this problem. Compared with ant colony algorithm and tabu search algorithm, the proposed algorithm is demonstrated to obtain optimal solution more effectively through the simulation, and it is an effective method to solve split delivery vehicle routing problem.%针对传统的车辆路径问题通常假设客户的需求不能拆分,即客户的需求由一辆车满足,而实际上通过需求的拆分可使需要的车辆数更少,从而降低配送成本的问题,分析了需求可拆分的车辆路径问题的解的特征,证明了客户需求不宜拆分应满足的条件,设计了符合解的特征的聚类算法,并对其求解.通过实验仿真,将所提出的聚类算法与蚁群算法和禁忌搜索算法进行比较,所得结果表明了所提出的算法可以更有效地求得需求可拆分车辆路径问题的优化解,是解决需求町拆分车辆路径问题的有效方法.

  20. In-Use and Vehicle Dynamometer Evaluation and Comparison of Class 7 Hybrid Electric and Conventional Diesel Delivery Trucks

    Energy Technology Data Exchange (ETDEWEB)

    Burton, J.; Walkowicz, K.; Sindler, P.; Duran, A.


    This study compared fuel economy and emissions between heavy-duty hybrid electric vehicles (HEVs) and equivalent conventional diesel vehicles. In-use field data were collected from daily fleet operations carried out at a FedEx facility in California on six HEV and six conventional 2010 Freightliner M2-106 straight box trucks. Field data collection primarily focused on route assessment and vehicle fuel consumption over a six-month period. Chassis dynamometer testing was also carried out on one conventional vehicle and one HEV to determine differences in fuel consumption and emissions. Route data from the field study was analyzed to determine the selection of dynamometer test cycles. From this analysis, the New York Composite (NYComp), Hybrid Truck Users Forum Class 6 (HTUF 6), and California Air Resource Board (CARB) Heavy Heavy-Duty Diesel Truck (HHDDT) drive cycles were chosen. The HEV showed 31% better fuel economy on the NYComp cycle, 25% better on the HTUF 6 cycle and 4% worse on the CARB HHDDT cycle when compared to the conventional vehicle. The in-use field data indicates that the HEVs had around 16% better fuel economy than the conventional vehicles. Dynamometer testing also showed that the HEV generally emitted higher levels of nitric oxides than the conventional vehicle over the drive cycles, up to 77% higher on the NYComp cycle (though this may at least in part be attributed to the different engine certification levels in the vehicles tested). The conventional vehicle was found to accelerate up to freeway speeds over ten seconds faster than the HEV.

  1. Retargeting Clostridium difficile Toxin B to Neuronal Cells as a Potential Vehicle for Cytosolic Delivery of Therapeutic Biomolecules to Treat Botulism

    Directory of Open Access Journals (Sweden)

    Greice Krautz-Peterson


    Full Text Available Botulinum neurotoxins (BoNTs deliver a protease to neurons which can cause a flaccid paralysis called botulism. Development of botulism antidotes will require neuronal delivery of agents that inhibit or destroy the BoNT protease. Here, we investigated the potential of engineering Clostridium difficile toxin B (TcdB as a neuronal delivery vehicle by testing two recombinant TcdB chimeras. For AGT-TcdB chimera, an alkyltransferase (AGT was appended to the N-terminal glucosyltransferase (GT of TcdB. Recombinant AGT-TcdB had alkyltransferase activity, and the chimera was nearly as toxic to Vero cells as wild-type TcdB, suggesting efficient cytosolic delivery of the AGT/GT fusion. For AGT-TcdB-BoNT/A-Hc, the receptor-binding domain (RBD of TcdB was replaced by the equivalent RBD from BoNT/A (BoNT/A-Hc. AGT-TcdB-BoNT/A-Hc was >25-fold more toxic to neuronal cells and >25-fold less toxic to Vero cells than AGT-TcdB. Thus, TcdB can be engineered for cytosolic delivery of biomolecules and improved targeting of neuronal cells.

  2. Rheological phenomena in focus

    CERN Document Server

    Boger, DV


    More than possibly any other scientific discipline, rheology is easily visualized and the relevant literature contains many excellent photographs of unusual and often bizarre phenomena. The present book brings together these photographs for the first time. They are supported by a full explanatory text. Rheological Phenomena in Focus will be an indispensable support manual to all those who teach rheology or have to convince colleagues of the practical relevance of the subject within an industrial setting. For those who teach fluid mechanics, the book clearly illustrates the difference be

  3. Theory of rheology (United States)

    Hutton, J. F.


    The structure of the modern theory of rheology is discussed to show the assumptions and limitations. Rheology is discussed as a branch of continuum mechanics to determine the relationships between stress, strain, and strain rate which will give a closer representation of lubricant properties than the Newtonian flow equation. Rheology is also investigated as a branch of chemical physics. Consideration is limited to those theories of nonpolymeric and polymeric fluids which can represent viscoelasticity in terms of identifiable and measureable molecular characteristics. The possibility that elastic liquids may rupture in shear and linear tension analogous to the failure of solids is proposed.

  4. Hydraulic Hybrid Vehicles (United States)

    EPA and the United Parcel Service (UPS) have developed a hydraulic hybrid delivery vehicle to explore and demonstrate the environmental benefits of the hydraulic hybrid for urban pick-up and delivery fleets.

  5. Rheology of Structured Oils (United States)

    Kelbaliev, G. I.; Rasulov, S. R.; Rzaev, A. G.; Mustafaeva, G. R.


    Rheological models of structured oils are proposed and compared with available experimental data on oils from different deposits. It is shown that structured oils can possess properties of Bingham and power-law non-Newtonian fluids.

  6. Rheology of waxy oils

    Energy Technology Data Exchange (ETDEWEB)

    Alicke, Alexandra A.; Marchesini, Flavio H.; Mendes, Paulo R. de Souza [Pontificia Universidade Catolica do Rio de Janeiro (PUC-Rio), RJ (Brazil)], e-mails:,; Ziglio, Claudio [Petrobras Research Center, Rio de Janeiro, RJ (Brazil)], e-mail:


    It is well known that below the crystallization temperature the rheology of waxy oils changes from Newtonian to an extremely complex non-Newtonian behavior, which is shear-rate and temperature-history dependent. Along the last decades a lot of effort has been put into obtaining reliable rheological measurements from different oils so as to understand the yielding of waxy oils as well as the effects of shear and temperature histories on rheological properties, such as viscosity, yield stress, storage and loss moduli. In this paper we examine in detail the related literature, discussing the main reasons for some disagreements concerning the history effects on the flow properties of waxy oils. In addition, we performed temperature ramps and stress-amplitude-sweep tests and compared the results obtained with the main trends observed, highlighting the effects of cooling and shear on the microstructure and consequently on the rheological properties of these oils. (author)

  7. Polyelectrolytes thermodynamics and rheology

    CERN Document Server

    P M, Visakh; Picó, Guillermo Alfredo


    This book discusses current development of theoretical models and experimental findings on the thermodynamics of polyelectrolytes. Particular emphasis is placed on the rheological description of polyelectrolyte solutions and hydrogels.

  8. 最小化车辆数的供应商直接配送策略%Strategy for supplier's direct delivery to minimize the number of vehicles

    Institute of Scientific and Technical Information of China (English)

    余海燕; 徐寅峰


    研究零售商具有周期性需求,供应商采用直接配送策略情形下以最小化车辆数为目标的供应商配送问题.给出并证明了一辆车存在可行日程安排时零售商最大配送周期满足的充分条件,在此基础上,运用将零售商集合划分成尽量少的子集合的思想,保证每个子集合中零售商都可用一辆车配送货物,设计了子集划分策略.证明在任何情况下,子集划分策略给出的车辆数都不会超过最少需要的车辆数的2.29倍.%We present a replenishment scheduling problem to minimize the number of vehicles, when the retailers face a periodic demand and the supplier adopts direct delivery strategy. First, we prove a sufficient condition of one vehicle to replenish several retailers. Based on this sufficient condition, we design a subsets dividing strategy, which divides the set of all the retailers into several subsets and ensures one vehicle can replenish the entire retailers in any one subset. Further, we prove the number of vehicles which is given by our strategy would not exceed 2.29 times of the minimal number of vehicles.

  9. Rheology of Superplastic Ceramics

    Institute of Scientific and Technical Information of China (English)


    Constitutive equation of rheglogy describing a phenomenological level of superplastic deformation as functional correlation between tensor components of stress and strain rate has been analyzed for the case of superplastic ceramic flow. Rheological properties of material are taken into account by means of scalar rheological coefficients of shear and volume viscosity, which are functions of temperature, effective stress (or strain rate) and density of material.

  10. Synthetic surfactant- and cross-linker-free preparation of highly stable lipid-polymer hybrid nanoparticles as potential oral delivery vehicles. (United States)

    Wang, Taoran; Xue, Jingyi; Hu, Qiaobin; Zhou, Mingyong; Chang, Chao; Luo, Yangchao


    The toxicity associated with concentrated synthetic surfactants and the poor stability at gastrointestinal condition are two major constraints for practical applications of solid lipid nanoparticles (SLN) as oral delivery vehicles. In this study, a synthetic surfactant-free and cross-linker-free method was developed to fabricate effective, safe, and ultra-stable lipid-polymer hybrid nanoparticles (LPN). Bovine serum albumin (BSA) and dextran varying in molecular weights were first conjugated through Maillard reaction and the conjugates were exploited to emulsify solid lipid by a solvent diffusion and sonication method. The multilayer structure was formed by self-assembly of BSA-dextran micelles to envelope solid lipid via a pH- and heating-induced facile process with simultaneous surface deposition of pectin. The efficiency of different BSA-dextran conjugates was systematically studied to prepare LPN with the smallest size, the most homogeneous distribution and the greatest stability. The molecular interactions were characterized by Fourier transform infrared and fluorescence spectroscopies. Both nano spray drying and freeze-drying methods were tested to produce spherical and uniform pectin-coated LPN powders that were able to re-assemble nanoscale structure when redispersed in water. The results demonstrated the promise of a synthetic surfactant- and cross-linker-free technique to prepare highly stable pectin-coated LPN from all natural biomaterials as potential oral delivery vehicles.

  11. Carboxymethylcellulose (CMC) formed nanogels with branched poly(ethyleneimine) (bPEI) for inhibition of cytotoxicity in human MSCs as a gene delivery vehicles. (United States)

    Yang, Han Na; Park, Ji Sun; Jeon, Su Yeon; Park, Keun-Hong


    Specific vehicles are necessary for safe and efficient gene transfection into cells. Nano-type hydrogels (nanogel) comprising carboxymethylcellulose (CMC) complexed with branched type cationic poly(ethleneimine) (bPEI) were used as gene delivery vehicles. When complexes of CMC and bPEI were used in vitro, CMC showed nano-gel type properties, as shown by the results of a viscosity test, and bPEI showed low cytotoxicity comparing to bPEI alone. Together, these properties are shown to maintain high gene transfection efficiency. In viability experiments using three types of adult stem cells, cell viability varied depending on the branch form of PEI and whether or not it is in a complex with CMC. The gene delivery efficacy showed that the CMC nanogel complexed with bPEI (CMC-bPEI) showed more uptaking and gene transfection ability in hMSCs comparing to bPEI alone. In osteogenesis, the CMC-bPEI complexed with OSX pDNA showed more easy internalization than bPEI alone complexed with OSX pDNA in hMSCs. Specific genes and proteins related in osteogenic differentiation were expressed in hMSCs when the CMC-bPEI complexed with OSX pDNA was used.

  12. Bottlebrush Polymers: Synthesis, Rheology, and Self-Assembly (United States)

    Dalsin, Samuel J.

    Bottlebrush polymers are comb-like molecules with a high density of side chains grafted along a central backbone. Due to their unique conformational properties, bottlebrush polymers have become attractive candidates for developing new photonic bandgap materials, nanotubes and nanowires, or drug delivery vehicles, to name a few. This dissertation primarily investigates the rheological properties and self-assembly behavior of bottlebrush polymer molecules made using a variety of different polymerization routes. A considerable portion of the work is directed towards the linear rheology of model, polyolefin-based bottlebrush polymers with independently varied branch and backbone lengths. These studies demonstrate how the tight spacing between branch points effectively precludes backbone entanglement in the polymer melts, but it does not inhibit the formation of entanglements among the branched side chains. Furthermore, the relaxation profiles reveal transient scaling behavior in which the dynamics transition from Zimm-like to Rouse-like at increasing relaxation times. These results highlight the distinct conformational character of bottlebrushes at different length scales. The latter parts of this work report on the self-assembly behavior of bottlebrush diblock polymers composed of atactic polypropylene and polystyrene side chains. The diblock samples are analyzed using small-angle X-ray scattering and atomic force microscopy. Nearly all of the samples display strong segregation between the two blocks, owing to the large molar mass of typical bottlebrush polymers. Consequently, only one experimental sample displays an accessible order-disorder transition temperature. The strong segregation is also shown to affect the ability of large bottlebrush diblocks to readily achieve well-ordered nanostructures by self-assembly. Finally, results of the most symmetric (by volume fraction) diblock samples are compared with predictions of a newly developed self-consistent field

  13. Delivery of esomeprazole magnesium through nasogastric and gastrostomy tubes using an oral liquid vehicle as a suspending agent in vitro. (United States)

    Shah, Sachin A; Sander, Stephen; Coleman, Craig I; White, C Michael


    The optimal delivery medium for esomeprazole magnesium enteric-coated pellets dispersed in various concentrations of Ora-Plus suspension through commonly used nasogastric and gastrostomy tubes using a previously used standardized in vitro protocol was studied. The study was conducted in two phases. In phase A, 60 size 14 French nasogastric tubes were used to compare esomeprazole pellet delivery via tap water or 30, 50, or 70% Ora-Plus concentrations (15 tubes for each). In phase B, tap water and the concentration that yielded the best pellet delivery from phase A were used with the narrower size 8 and shorter size 20 French tubes. In both phases, the appropriate volume of water was added. All capsules were assumed to have 1,240 pellets. At the end of each administration, pellet retention counts were performed. The results showed excellent delivery of esomeprazole pellets using water as a medium for tube delivery. When compared with tap water as a delivery medium, no differences in pellet retention were observed when 30% and 50% Ora-Plus were used; thus, these Ora-Plus concentrations are feasible alternatives to tap water for nasogastric tube delivery of esomeprazole pellets. Administration of esomeprazole magnesium enteric-coated pellets dispersed in tap water or Ora-Plus through size 14 French nasogastric tubes in vitro delivered over 99% of capsule contents, regardless of the Ora-Plus concentration used. For immediate bedside administration, Ora-Plus at 50% concentration is a feasible alternative to water when delivering the pellets through size 14 French tubes, while 30% Ora-Plus is an alternative to water for all tubes studied.

  14. Structured triglyceride vehicles for oral delivery of halofantrine: examination of intestinal lymphatic transport and bioavailability in conscious rats

    DEFF Research Database (Denmark)

    Holm, René; Porter, Christopher J H; Müllertz, Anette


    animals, and this was most pronounced for the animals dosed with the structured triglycerides. CONCLUSIONS: Using MLM as vehicle increases the portal absorption of halofantrine and results in similar lymphatic transport levels when compared to sunflower oil. Total absorption when assessed as absorption...... in the blood plus lymphatic transport for halofantrine after administration in the MLM triglyceride was higher than after administration in sunflower oil.......PURPOSE: To compare the influence of triglyceride vehicle intramolecular structure on the intestinal lymphatic transport and systemic absorption of halofantrine in conscious rats. METHODS: Conscious, lymph cannulated and nonlymph cannulated rats were dosed orally with three structurally different...

  15. Synthesis and characterization of novel water-soluble polyamide based on spermine and aspartic acid as a potential gene delivery vehicle

    Directory of Open Access Journals (Sweden)


    Full Text Available We developed a novel and convenient method for the synthesis of a potentially safe non-viral gene delivery vehicle based on the cationic block copolymer of spermine and aspartic acid (ASSP and coupled it with polyethylene glycol (PEG. The copolymer ASSP was prepared by direct polycondensation in the ionic liquid, butylmethylimidazolium hexafluorophosphate, using triphenyl phosphite as the condensing agent under mild reaction conditions. The highly hydrophobic ASSP was transformed into a water soluble hydrophilic micelle by coupling ASSP with polyethylene glycol (PEG using the same ionic liquid and 1,1-carbonyl diimidazole as the condensing agent without harsh conditions. The polycationic ASSP-PEG was then used to condense calf thymus and plasmid deoxyribonuclceic acids (DNAs in Tris-HCl buffer (pH 7.4 to get a series of block ionomer complexes with various charge ratios. The physicochemical properties of the copolymer micelle and the DNA polyplexes were studied using fourier transform-infrared (FTIR, nuclear magnetic resonance (NMR and circular dichroism (CD spectroscopy, matrix assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS, differential scanning calorimetry (DSC, transmission electron microscopy (TEM and particle size measurements. It was observed that the DNA was condensed to compact particles by its interaction with the copolymer. Since DNA condensation to nano/micrometer sized particles is essential for gene delivery, our results indicate a potential use of the copolymer for gene delivery applications.

  16. PEGylated dendritic diaminocyclohexyl-platinum (II) conjugates as pH-responsive drug delivery vehicles with enhanced tumor accumulation and antitumor efficacy. (United States)

    Pan, Dayi; She, Wenchuan; Guo, Chunhua; Luo, Kui; Yi, Qiangying; Gu, Zhongwei


    Environmentally responsive peptide dendrimers loaded with drugs are suitable candidates for cancer therapy. In this study, we report the preparation and characterization of mPEGylated peptide dendrimer-linked diaminocyclohexyl platinum (II) (dendrimer-DACHPt) conjugates as pH-responsive drug delivery vehicles for tumor suppression in mice. The DACHPt has a molecular structure, is and activity closely related to oxaliplatin and was linked to dendrimer via N,O-chelate coordination. The products were pH-responsive and released drug significantly faster in acidic environments (pH 5.0) than pH 7.4. Consequently, the conjugates suppressed tumor growth better than clinical oxaliplatin(®) without inducing toxicity in an SKOV-3 human ovarian cancer xenograft. Through the systemic delivery of conjugates, 25-fold higher tumor platinum uptake at 36 h post-injection was seen observed due to the enhanced permeability and retention (EPR) effect thereby remarkably enhancing the therapeutic indexes of this small-molecule drug. Thus, the mPEGylated peptide dendrimer-linked DACH-platinum conjugates are novel potential drug delivery systems with implications in future ovarian cancer therapy.

  17. Virosome, a hybrid vehicle for efficient and safe drug delivery and its emerging application in cancer treatment

    Directory of Open Access Journals (Sweden)

    Liu Hanqing


    Full Text Available A virosome is an innovative hybrid drug delivery system with advantages of both viral and non-viral vectors. Studies have shown that a virosome can carry various biologically active molecules, such as nucleic acids, peptides, proteins and small organic molecules. Targeted drug delivery using virosome-based systems can be achieved through surface modifications of virosomes. A number of virosome- -based prophylactic and therapeutic products with high safety profiles are currently available in the market. Cancer treatment is a big battlefield for virosome-based drug delivery systems. This review provides an overview of the general concept, preparation procedures, working mechanisms, preclinical studies and clinical applications of virosomes in cancer treatment.

  18. Nanocarriers for treatment of ocular neovascularization in the back of the eye: new vehicles for ophthalmic drug delivery. (United States)

    Shen, Hsin-Hui; Chan, Elsa C; Lee, Jia Hui; Bee, Youn-Shen; Lin, Tsung-Wu; Dusting, Gregory J; Liu, Guei-Sheung


    Pathologic neovascularization of the retina is a major cause of substantial and irreversible loss of vision. Drugs are difficult to deliver to the lesions in the back of the eye and this is a major obstacle for the therapeutics. Current pharmacological approach involves an intravitreal injection of anti-VEGF agents to prevent aberrant growth of blood vessels, but it has limitations including therapeutic efficacy and side-effects associated with systemic exposure and invasive surgery. Nanotechnology provides novel opportunities to overcome the limitations of conventional delivery system to reach the back of the eye through fabrication of nanostructures capable of encapsulating and delivering small molecules. This review article introduces various forms of nanocarrier that can be adopted by ocular drug delivery systems to improve current therapy. The application of nanotechnology in medicine brings new hope for ocular drug delivery in the back of the eye to manage the major causes of blindness associated with ocular neovascularization.

  19. Microemulsions as vehicles for topical administration of voriconazole: formulation and in vitro evaluation. (United States)

    El-Hadidy, Gladious Naguib; Ibrahim, Howida Kamal; Mohamed, Magdi Ibrahim; El-Milligi, Mohamed Farid


    This work was undertaken to investigate microemulsion (ME) as a topical delivery system for the poorly water-soluble voriconazole. Different ME components were selected for the preparation of plain ME systems with suitable rheological properties for topical use. Two permeation enhancers were incorporated, namely sodium deoxycholate or oleic acid. Drug-loaded MEs were evaluated for their physical appearance, pH, rheological properties and in vitro permeation studies using guinea pig skin. MEs based on polyoxyethylene(10)oleyl ether (Brij 97) as the surfactant showed pseudoplastic flow with thixotropic behavior and were loaded with voriconazole. Jojoba oil-based MEs successfully prolonged voriconazole release up to 4 h. No significant changes in physical or rheological properties were recorded on storage for 12 months at ambient conditions. The presence of permeation enhancers favored transdermal rather than dermal delivery. Sodium deoxycholate was more effective than oleic acid for enhancing the voriconazole permeation. Voriconazole-loaded MEs, with and without enhancers, showed significantly better antifungal activity against Candida albicans than voriconazole supersaturated solution. In conclusion, the studied ME formulae could be promising vehicles for topical delivery of voriconazole.

  20. Rheology of Supramolecular Polymers

    DEFF Research Database (Denmark)

    Shabbir, Aamir

    efficient processes or biomedical areas. Design and development of supramolecular polymers using ionic, hydrogen bonding or transition metal complexes with tailored properties requires deep understanding of dynamics both in linear and non-linear deformations. While linear rheology is important to understand......) hydrogen bonding polymers, and (b) ionic bonding polymers (hereafter termed as ionomers). We study linear and non-linear rheology fora model system of entangled pure poly(n-butyl acrylate), PnBA, homopolymer andfour poly(acrylic acid), PnBA-PAA, copolymers with varying AA side groups synthesizedvia...

  1. Polydopamine-based surface modification of mesoporous silica nanoparticles as pH-sensitive drug delivery vehicles for cancer therapy. (United States)

    Chang, Danfeng; Gao, Yongfeng; Wang, Lijun; Liu, Gan; Chen, Yuhan; Wang, Teng; Tao, Wei; Mei, Lin; Huang, Laiqiang; Zeng, Xiaowei


    A novel pH-sensitive drug delivery system of mesoporous silica nanoparticles (MSNs) which were modified by polydopamine (PDA) for controlled release of cationic amphiphilic drug desipramine (DES) was prepared. MSNs-DES-PDA were characterized in terms of size, size distribution, surface morphology, BET surface area, mesoporous size and pore volume, drug loading content and in vitro drug release profile. MSNs-DES-PDA had high drug loading content and pH sensitivity. The DES release profiles of MSNs-DES and MSNs-DES-PDA were totally different, and the drug release of MSNs-DES-PDA accelerated with increasing acidity. MSNs-DES-PDA can be internalized into cells. In vitro experiments demonstrated that MSNs-DES-PDA had higher cytotoxicity and inhibitory effects on acid sphingomyelinase than those of free DES. This drug delivery system was beneficial for controlled release and cancer therapy.

  2. 物流配送车辆调度问题算法综述%Research on Algorithm of Delivery Vehicle Routing Problems

    Institute of Scientific and Technical Information of China (English)

    陈君兰; 叶春明


    Delivery vehicle routing problems (VRP) is a kind of optimization problems, aiming at solving the vehicle routing problems in delivery section. And they have been a focus of research in logistics control optimization recently. After summarize different kinds of VRP, the article gives the relevant general models. The character and the application of genetic algorithm, simulated annealing, tabu search, ant colony algorithm, particle swarm optimization are analyzed and the current possibilities to solve VRP are also discussed. Finally, the development of VRP solution is presented, and point out that improved combined algorithm as well as new algorithm will be important measures to solve VRP.%配送车辆调度优化问题旨在解决配送中路径和车辆调度问题的一类组合优化问题,是近年来物流控制优化领域的研究热点。文章对运输调度问题进行了分类总结,给出总体模型的概括描述,分析遗传算法、模拟退火算法、禁忌搜索算法、蚁群算法和微粒群算法的特点及其在求解配送车辆调度优化问题中的求解思路,并讨论了其求解现状,对未来研究方向进行展望,指出改进混合现有算法,开拓新算法将是更有效解决配送车辆调度问题的好方法。

  3. 间充质干细胞作为载体用于肿瘤治疗%Mesenchymal stem cells: a delivery vehicle for cancer therapy

    Institute of Scientific and Technical Information of China (English)

    徐应龙; 王坚


    干细胞有无限制自我更新以及分化成多种祖细胞的能力.间充质干细胞( MSCs)能特异地向多种肿瘤以及它们的转移灶迁移,并且它们的迁移是遍及全身的.借助这一特性,基因修饰MSCs可用作特异性靶向药物的载体并表达抗癌因子以抑制肿瘤生长.然而,许多问题和确切的机制尚待解答.本文主要回顾MSCs归巢的机制、MSCs作为载体用于肿瘤治疗以及MSCs与无活性药物载体相比的优缺点.MSCs作为载体可能成为一种细胞治疗,在未来的肿瘤治疗中发挥作用.%Stem cells possess unlimited self-renewal properties and the ability to produce multiple differentiation progenitors. Mesenchymal stem cells (MSCs) can specifically migrate to multiple kinds of tumors and their metastases in a systemic manner(to all parts of the body). Therefore genetically modified MSCs can serve as vehicle of anticancer factors to inhibit growth of tumor. But many questions remain to be answered and the precise mechanisms remain unclear. This paper reviews the mechanism of MSC homing, MSCs as delivery vectors for cancer therapy and its advantages over traditional drug vehicle. MSCs as delivery vectors can be used for cellular therapy in future cancer treatment.

  4. Assesment of mucoadhesion using small deformation rheology revisited

    DEFF Research Database (Denmark)

    Harloff-Helleberg, Stine; Vissing, Karina Juul; Nielsen, Hanne Mørck


    This work revisits the commonly used approach to assess mucoadhesion in drug delivery by small deformation rheology. The results show that biosimilar mucus serves as a more predictive mucus model system when compared to mucin suspensions. Data is fitted including error propagation, different from...

  5. BNNTs under the influence of external electric field as potential new drug delivery vehicle of Glu, Lys, Gly and Ser amino acids: A first-principles study (United States)

    Farmanzadeh, Davood; Ghazanfary, Samereh


    The interaction of Glu (Glutamic acid), Lys (Lysine), Gly (Glycine) and Ser (Serine) amino acids with different polarities and (9, 0) zigzag single-wall boron nitride nanotubes (BNNTs) with various lengths in the presence and absence of external electric field (EF) in gas and solvent phases, are studied using density functional theory. It is found that interaction of Glu, Lys, Gly and Ser amino acids with BNNTs in both phases is energetically favorable. From solvation energy calculations, it can be seen that the BNNTs/amino acid complex dissolution in water is spontaneous. The adsorption energies and quantum molecular descriptors changed in the presence of external EF. Therefore, the study of BNNTs/amino acid complex under influence of external electric field is very important in proposing or designing new drug delivery systems in the presence of external EF. Results indicate that Glu, Lys, Gly and Ser amino acids can be adsorbed considerably on the BNNTs in the existence of external electric field. Our results showed that the BNNTs can act as a suitable drug delivery vehicle of Glu, Lys, Gly and Ser amino acids within biological systems and strength of adsorption and rate of drug release can be controlled by the external EF.

  6. BNNTs under the influence of external electric field as potential new drug delivery vehicle of Glu, Lys, Gly and Ser amino acids: A first-principles study

    Energy Technology Data Exchange (ETDEWEB)

    Farmanzadeh, Davood, E-mail:; Ghazanfary, Samereh


    Graphical abstract: - Highlights: • Solvation energies show that the BNNTs/amino acids complex stabilizes in presence of solvent. • The adsorption process is sensitive to the external electric field. • The electric field is a suitable method for adsorption and storage of amino acids on BNNTs. - Abstract: The interaction of Glu (Glutamic acid), Lys (Lysine), Gly (Glycine) and Ser (Serine) amino acids with different polarities and (9, 0) zigzag single-wall boron nitride nanotubes (BNNTs) with various lengths in the presence and absence of external electric field (EF) in gas and solvent phases, are studied using density functional theory. It is found that interaction of Glu, Lys, Gly and Ser amino acids with BNNTs in both phases is energetically favorable. From solvation energy calculations, it can be seen that the BNNTs/amino acid complex dissolution in water is spontaneous. The adsorption energies and quantum molecular descriptors changed in the presence of external EF. Therefore, the study of BNNTs/amino acid complex under influence of external electric field is very important in proposing or designing new drug delivery systems in the presence of external EF. Results indicate that Glu, Lys, Gly and Ser amino acids can be adsorbed considerably on the BNNTs in the existence of external electric field. Our results showed that the BNNTs can act as a suitable drug delivery vehicle of Glu, Lys, Gly and Ser amino acids within biological systems and strength of adsorption and rate of drug release can be controlled by the external EF.

  7. Therapeutic Use of 3β-[N-(N',N'-Dimethylaminoethane) Carbamoyl] Cholesterol-Modified PLGA Nanospheres as Gene Delivery Vehicles for Spinal Cord Injury. (United States)

    Gwak, So-Jung; Yun, Yeomin; Yoon, Do Heum; Kim, Keung Nyun; Ha, Yoon


    Gene delivery holds therapeutic promise for the treatment of neurological diseases and spinal cord injury. Although several studies have investigated the use of non-viral vectors, such as polyethylenimine (PEI), their clinical value is limited by their cytotoxicity. Recently, biodegradable poly (lactide-co-glycolide) (PLGA) nanospheres have been explored as non-viral vectors. Here, we show that modification of PLGA nanospheres with 3β-[N-(N',N'-dimethylaminoethane) carbamoyl] cholesterol (DC-Chol) enhances gene transfection efficiency. PLGA/DC-Chol nanospheres encapsulating DNA were prepared using a double emulsion-solvent evaporation method. PLGA/DC-Chol nanospheres were less cytotoxic than PEI both in vitro and in vivo. DC-Chol modification improved the uptake of nanospheres, thereby increasing their transfection efficiency in mouse neural stem cells in vitro and rat spinal cord in vivo. Also, transgene expression induced by PLGA nanospheres was higher and longer-lasting than that induced by PEI. In a rat model of spinal cord injury, PLGA/DC-Chol nanospheres loaded with vascular endothelial growth factor gene increased angiogenesis at the injury site, improved tissue regeneration, and resulted in better recovery of locomotor function. These results suggest that DC-Chol-modified PLGA nanospheres could serve as therapeutic gene delivery vehicles for spinal cord injury.

  8. Activated Sludge Rheology

    DEFF Research Database (Denmark)

    Ratkovich, Nicolas Rios; Horn, Willi; Helmus, Frank


    Rheological behaviour is an important fluid property that severely impacts its flow behaviour and many aspects related to this. In the case of activated sludge, the apparent viscosity has an influence on e.g. pumping, hydrodynamics, mass transfer rates, sludge-water separation (settling and filtr...

  9. Rheology of concentrated biomass (United States)

    J.R. Samaniuk; J. Wang; T.W. Root; C.T. Scott; D.J. Klingenberg


    Economic processing of lignocellulosic biomass requires handling the biomass at high solids concentration. This creates challenges because concentrated biomass behaves as a Bingham-like material with large yield stresses. Here we employ torque rheometry to measure the rheological properties of concentrated lignocellulosic biomass (corn stover). Yield stresses obtained...

  10. Patient-derived mesenchymal stem cells as delivery vehicles for oncolytic virotherapy: novel state-of-the-art technology. (United States)

    Ramírez, Manuel; García-Castro, Javier; Melen, Gustavo J; González-Murillo, África; Franco-Luzón, Lidia


    Oncolytic virotherapy is gaining interest in the clinic as a new weapon against cancer. In vivo administration of oncolytic viruses showed important limitations that decrease their effectiveness very significantly: the antiviral immune response causes the elimination of the therapeutic effect, and the poor natural ability of oncolytic viruses to infect micrometastatic lesions significantly minimizes the effective dose of virus. This review will focus on updating the technical and scientific foundations of one of the strategies developed to overcome these limitations, ie, using cells as vehicles for oncolytic viruses. Among many candidates, a special type of adult stem cell, mesenchymal stem cells (MSCs), have already been used in the clinic as cell vehicles for oncolytic viruses, partly due to the fact that these cells are actively being evaluated for other indications. MSC carrier cells are used as Trojan horses loaded with oncoviruses, are administered systemically, and release their cargos at the right places. MSCs are equipped with an array of molecules involved in cell arrest in the capillaries (integrins and selectins), migration toward specific parenchymal locations within tissues (chemokine receptors), and invasion and degradation of the extracellular matrix (proteases). In addition to anatomical targeting capacity, MSCs have a well-recognized role in modulating immune responses by affecting cells of the innate (antigen-presenting cells, natural killer cells) and adaptive immune system (effector and regulatory lymphocytes). Therefore, carrier MSCs may also modulate the immune responses taking place after therapy, ie, the antiviral and the antitumor immune responses.

  11. Brain-derived neurotrophic factor (BDNF) gene delivery into the CNS using bone marrow cells as vehicles in mice. (United States)

    Makar, T K; Trisler, D; Eglitis, M A; Mouradian, M M; Dhib-Jalbut, S


    Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, is protective in animal models of neurodegenerative diseases. However, BDNF has a short half-life and its efficacy in the CNS when delivered peripherally is limited due to the blood-brain barrier. In the present study, bone marrow cells were used as vehicles to deliver the BDNF gene into the CNS. Marrow cells obtained from 6 to 8 week-old SJL/J mice were transduced with BDNF expressing pro-virus. RT-PCR analysis revealed that BDNF mRNA was expressed in transduced but not in non-transduced marrow cells. Additionally, virus transduced marrow cells expressed the BDNF protein (296+/-1.2 unit/ml). BDNF-transduced marrow cells were then transplanted into irradiated mice through the tail vein. Three months post-transplantation, significant increases in BDNF as well as glutamic acid decarboxylase (GAD(67)) mRNA were detected in the brains of BDNF transplanted mice compared to untransplanted animals, indicating biological activity of the BDNF transgene. Thus, bone marrow cells can be used as vehicles to deliver the BDNF gene into the brain with implications for the treatment of neurological diseases.

  12. Nanodiamond decorated liposomes as highly biocompatible delivery vehicles and a comparison with carbon nanotubes and graphene oxide (United States)

    Wang, Feng; Liu, Juewen


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

  13. Smart materials on the way to theranostic nanorobots: Molecular machines and nanomotors, advanced biosensors, and intelligent vehicles for drug delivery. (United States)

    Sokolov, Ilya L; Cherkasov, Vladimir R; Tregubov, Andrey A; Buiucli, Sveatoslav R; Nikitin, Maxim P


    Theranostics, a fusion of two key parts of modern medicine - diagnostics and therapy of the organism's disorders, promises to bring the efficacy of medical treatment to a fundamentally new level and to become the basis of personalized medicine. Extrapolating today's progress in the field of smart materials to the long-run prospect, we can imagine future intelligent agents capable of performing complex analysis of different physiological factors inside the living organism and implementing a built-in program thereby triggering a series of therapeutic actions. These agents, by analogy with their macroscopic counterparts, can be called nanorobots. It is quite obscure what these devices are going to look like but they will be more or less based on today's achievements in nanobiotechnology. The present Review is an attempt to systematize highly diverse nanomaterials, which may potentially serve as modules for theranostic nanorobotics, e.g., nanomotors, sensing units, and payload carriers. Biocomputing-based sensing, externally actuated or chemically "fueled" autonomous movement, swarm inter-agent communication behavior are just a few inspiring examples that nanobiotechnology can offer today for construction of truly intelligent drug delivery systems. The progress of smart nanomaterials toward fully autonomous drug delivery nanorobots is an exciting prospect for disease treatment. Synergistic combination of the available approaches and their further development may produce intelligent drugs of unmatched functionality. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Patient-derived mesenchymal stem cells as delivery vehicles for oncolytic virotherapy: novel state-of-the-art technology

    Directory of Open Access Journals (Sweden)

    Ramírez M


    Full Text Available Manuel Ramírez,1 Javier García-Castro,2 Gustavo J Melen,1 África González-Murillo,1 Lidia Franco-Luzón1 1Oncohematología, Hospital Universitario Niño Jesús, 2Unidad de Biotecnología Celular, Instituto de Salud Carlos III, Madrid, Spain Abstract: Oncolytic virotherapy is gaining interest in the clinic as a new weapon against cancer. In vivo administration of oncolytic viruses showed important limitations that decrease their effectiveness very significantly: the antiviral immune response causes the elimination of the therapeutic effect, and the poor natural ability of oncolytic viruses to infect micrometastatic lesions significantly minimizes the effective dose of virus. This review will focus on updating the technical and scientific foundations of one of the strategies developed to overcome these limitations, ie, using cells as vehicles for oncolytic viruses. Among many candidates, a special type of adult stem cell, mesenchymal stem cells (MSCs, have already been used in the clinic as cell vehicles for oncolytic viruses, partly due to the fact that these cells are actively being evaluated for other indications. MSC carrier cells are used as Trojan horses loaded with oncoviruses, are administered systemically, and release their cargos at the right places. MSCs are equipped with an array of molecules involved in cell arrest in the capillaries (integrins and selectins, migration toward specific parenchymal locations within tissues (chemokine receptors, and invasion and degradation of the extracellular matrix (proteases. In addition to anatomical targeting capacity, MSCs have a well-recognized role in modulating immune responses by affecting cells of the innate (antigen-presenting cells, natural killer cells and adaptive immune system (effector and regulatory lymphocytes. Therefore, carrier MSCs may also modulate the immune responses taking place after therapy, ie, the antiviral and the antitumor immune responses. Keywords: virotherapy

  15. Attenuated Bordetella pertussis BPZE1 as a live vehicle for heterologous vaccine antigens delivery through the nasal route. (United States)

    Li, Rui; Lim, Annabelle; Alonso, Sylvie


    Whereas the great majority of the current vaccines are delivered through the parenteral route, mucosal administration has been increasingly considered for controlling infection and preventing disease. Mucosal vaccination can trigger both humoral and cell-mediated protection, not only at the targeted mucosal surface, but also systemically. In this regard, nasal vaccination has shown great potential. The live attenuated strain of Bordetella pertussis, BPZE1, is particularly attractive and promising as a nasal vaccine delivery vector of heterologous antigen vaccine candidates. BPZE1 was originally developed as a live nasal pertussis vaccine candidate, and is currently undergoing phase I clinical trial in human ( Highly adapted to the human respiratory tract and offering several potential protein carriers for presentation of the heterologous antigen vaccine candidates, BPZE1 represents an appealing platform for the development of live recombinant vaccines delivered via the nasal route that would confer simultaneous protection against pertussis and the targeted infectious disease(s).

  16. Delivery of completed irradiation vehicles and the quality assurance document to the High Flux Isotope Reactor for irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Petrie, Christian M. [Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States); McDuffee, Joel Lee [Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States); Katoh, Yutai [Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States); Terrani, Kurt A. [Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)


    This report details the initial fabrication and delivery of two Fuel Cycle Research and Development (FCRD) irradiation capsules (ATFSC01 and ATFSC02), with associated quality assurance documentation, to the High Flux Isotope Reactor (HFIR). The capsules and documentation were delivered by September 30, 2015, thus meeting the deadline for milestone M3FT-15OR0202268. These irradiation experiments are testing silicon carbide composite tubes in order to obtain experimental validation of thermo-mechanical models of stress states in SiC cladding irradiated under a prototypic high heat flux. This document contains a copy of the completed capsule fabrication request sheets, which detail all constituent components, pertinent drawings, etc., along with a detailed summary of the capsule assembly process performed by the Thermal Hydraulics and Irradiation Engineering Group (THIEG) in the Reactor and Nuclear Systems Division (RNSD). A complete fabrication package record is maintained by the THIEG and is available upon request.

  17. Lipid nanoparticles as vehicles for topical psoralen delivery: solid lipid nanoparticles (SLN) versus nanostructured lipid carriers (NLC). (United States)

    Fang, Jia-You; Fang, Chia-Lang; Liu, Chi-Hsien; Su, Yu-Han


    Solid lipid nanoparticles (SLN) were developed by using Precirol ATO 5 as the solid core of the particles for topical psoralen delivery. Nanostructured lipid carriers (NLC) consisting of Precirol and squalene, a liquid lipid, were also prepared for comparison. SLN and NLC showed respective mean particle sizes of approximately 300 and 200nm, respectively. Viscosity, polarity, and differential scanning calorimetry (DSC) studies were performed to characterize the physicochemical properties of the SLN and NLC. The viscosity of all nanoparticulate systems exhibited Newtonian behavior except the NLC with Tween 80 and soybean phospholipids as the emulsifiers (NLC-Tw). According to the DSC thermograms, the melting peak of Precirol shifted from 58 to 55 degrees C after incorporating squalene into the solid lipid cores (of NLC), which suggests defects in the crystalline lattice of the lipid cores and smaller particle sizes. Three psoralen derivatives for psoriasis treatments were loaded in SLN and NLC to examine their ability to permeate skin. The permeability of psoralens increased in the order of 8-methoxypsoralen (8-MOP)>5-methoxypsoralen (5-MOP)>4,5,8-trimethylpsoralen (TMP). Enhanced permeation and controlled release of psoralen delivery were both achieved using the NLC. The in vitro permeation results showed that NLC-Tw increased the 8-MOP flux 2.8 times over that of a conventional emulsion. Hyperproliferative or psoriasis-like skin produced by repeated strippings in the dorsal skin of nude mouse was also used as a permeation barrier. The results showed that the entrapment of 8-MOP in nanoparticulate systems could minimize the permeation differentiation between normal and hyperproliferative skin compared to the free drug in an aqueous control.

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

    Directory of Open Access Journals (Sweden)

    Naghmeh Naderi


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

  19. Rheological approach to targeting phenomena of lipoplexes. (United States)

    Sun, Yan


    Lipoplexes, the complexes of plasmid DNA with cationic lipids, are considered as an attractive alternative to viral delivery systems. However, synthesized lipoplexes showed several limitations including insufficient transfection, low reproducibility and low stability. Here we attempt to delineate the relationships between the synthesis process, morphology (e.g., shape and liquid crystal structure), and the transfection efficiency of lipoplexes with rheological technology. Mini-capillary viscometers with automatic measurement and control components were designed and used to study the morphology of lipoplexes at a macroscopical scale. In such a dilute macromolecule suspension system, the shape factor of lipoplex was correlated with the viscosity measurement. The results showed that the shape factors of lipoplexes were different with various molecular structures of cationic lipid and helper lipid. A quantitative relation was set up between the shape factors and the length of DNA/polyelectrolytes, which may help better explain lipoplexes formation. To improve the stability and reproducibility of lipoplexes, an incubation period was suggested before the use of lipoplex. A rheological method was introduced to fix the hydromechanical parameters so that the entire preparation and incubation process was carried out consistently. A laminar flow incubation environment was showed suitable for lipoplex preparation and helped improve lipoplex stability and minimize aggregation. Other flow incubations, such as turbulent flow or impinging flow, were more complicated and further study is necessary to fully understand them. In brief, the rheological methods can help reveal the mechanisms of lipoplex formation and advance the rational design of lipoplexes for pharmaceutical applications.

  20. Rheological properties of Cubic colloidal suspensions (United States)

    Boromand, Arman; Maia, Joao


    Colloidal and non-colloidal suspensions are ubiquitous in many industrial application. There are numerous studies on these systems to understand and relate their complex rheological properties to their microstructural evolution under deformation. Although most of the experimental and simulation studies are centered on spherical particles, in most of the industrial applications the geometry of the colloidal particles deviate from the simple hard sphere and more complex geometries exist. Recent advances in microfabrication paved the way to fabricate colloidal particles with complex geometries for applications in different areas such as drug delivery where the fundamental understanding of their dynamics has remained unexplored. In this study, using dissipative particle dynamics, we investigate the rheological properties of cubic (superball) particles which are modeled as the cluster of core-modified DPD particles. Explicit representation of solvent particles in the DPD scheme will conserve the full hydrodynamic interactions between colloidal particles. Rheological properties of these cubic suspensions are investigated in the dilute and semi-dilute regimes. The Einstein and Huggins coefficients for these particles with different superball exponent will be calculate which represent the effect of single particle's geometry and multibody interactions on viscosity, respectively. The response of these suspensions is investigated under simple shear and oscillatory shear where it is shown that under oscillation these particles tend to form crystalline structure giving rise to stronger shear-thinning behavior recently measured experimentally.

  1. Physicochemical effects of terpenes on organogel for transdermal drug delivery. (United States)

    Lim, Perry Fung Chye; Liu, Xiang Yang; Kang, Lifeng; Ho, Paul Chi Lui; Chan, Sui Yung


    It is accepted that terpenes are effective penetration enhancers to promote the passage of drugs or chemicals through the human skin barrier. However the physical and chemical changes of a pharmaceutical vehicle induced by the incorporation of terpenes have not been explored. Thus, this study examines the effects of three terpenes (linalool, cineole, limonene) on the rheology and chemical stability of an organogel composed of dibutyllauroylglutamide (GP1) and propylene glycol (PG). At a given GP1 concentration, oxygen-containing linalool and cineole decreased gel moduli (elastic and viscous) and brittleness, and the reverse was obtained for hydrocarbon limonene. Probably, linalool and cineole interfered with hydrogen bonding between GP1 molecules while limonene could have initiated a phase separation-mediated gelation, changing the gel morphology. Microcalorimetry detected minute heat endotherms for gels (with and without terpenes) subjected to accelerated heat testing. These heat changes could arise from a small degree of structural disruption of the gel network. Heat endotherms normalized with respect to GP1 content were used to assess gel chemical stability. Although the terpenes altered rheology, they did not significantly affect the chemical stability of the gels. This is the first in the literature that reports the effect of penetration enhancers, such as terpenes, on the physical, rheological and chemical characteristics of a model pharmaceutical formulation for topical and transdermal drug delivery.

  2. Rheology in lubrication (United States)

    Cheng, H. S.


    The rheological effects on lubrication are discussed. The types of lubrication considered are thick film hydrodynamic lubrication and thin film elastohydrodynamic lubrication. The temperature-viscosity, viscoelastic, shear-thinning, and normal stess effects on the lubrication of journal bearings are analyzed. A graph of the pressure distribution of viscoelastic liquids in journal bearings is provided. Mathematical models are developed to define the effects of various properties of the lubricants on friction reduction.

  3. Blood rheology and aging


    Oğuz K. Başkurt; Simmonds, Michael J. ; Meiselman, Herbert J.


    Journal of Geriatric Cardiology (2013) 10: 291301 ©2013 JGC All rights reserved;; | Journal of Geriatric Cardiology Review  Open Access  Blood rheology and aging Michael J. Simmonds1, Herbert J. Meiselman2, Oguz K. Baskurt3 1Heart Foundation Research Centre, Griffith Health Institute, Griffith University, Gold Coast, QLD 4222, Australia 2Department of Physiology and Biophysics, Keck School of Medicine, University of S...

  4. Experiments on Paint Rheology (United States)

    Hartranft, Thomas J.; Settles, Gary S.


    We seek a better understanding of the atomization of paints for purposes of limiting the environmental impact of spray painting. However, to do so one must confront both the shear and extensional rheology of mobile non-Newtonian fluids whose very composition is often complex and even unknown. A conventional Couette rheometer yields data on paint shear behavior, but no commercial instrument is available to measure the extensional viscosity, which is believed to govern ligamentary breakup in spray painting. Here a converging-flow extensional rheometer has been built for this purpose. Flow rate and orifice pressure drop are measured and related to the rheological properties of the fluid. At first, experience was gained by visualizing in this device the flow of clear aqueous solutions of both Newtonian (glycerol) and non-Newtonian (polyacrylamide) thickeners. Commercial latex and marine paints were then tested, with the goal of characterizing their extensional behavior and the hope that they might be replaceable by simpler aqueous rheological "substitute" fluids insofar as their atomization behavior is concerned. (Research supported by the US Navy via the Penn State Applied Research Laboratory.)

  5. Human embryonic stem cell-derived mesenchymal stem cells as cellular delivery vehicles for prodrug gene therapy of glioblastoma. (United States)

    Bak, Xiao Ying; Lam, Dang Hoang; Yang, Jingye; Ye, Kai; Wei, Esther Lee Xing; Lim, Sai Kiang; Wang, Shu


    Mesenchymal stem cells (MSCs) possess tumor-tropic properties and consequently have been used to deliver therapeutic agents for cancer treatment. Their potential in cancer therapy highlights the need for a consistent and renewable source for the production of uniform human MSCs suitable for clinical applications. In this study, we seek to investigate whether human embryonic stem cells can be used as a cell source to fulfill this goal. We generated MSC-like cells from two human embryonic stem cell lines, HuES9 and H1, and observed that MSC-like cells derived from human embryonic stem cells were able to migrate into human glioma intracranial xenografts after being injected into the cerebral hemisphere contralateral to the tumor inoculation site. We engineered these cells with baculoviral and lentiviral vectors, respectively, for transient and stable expression of the herpes simplex virus thymidine kinase gene. In tumor-bearing mice the engineered MSC-like cells were capable of inhibiting tumor growth and prolonging survival in the presence of ganciclovir after they were injected either directly into the xenografts or into the opposite hemisphere. Our findings suggest that human embryonic stem cell-derived MSCs may be a viable and attractive alternative for large-scale derivation of targeting vehicles for cancer therapy.

  6. Biodegradable PLGA85/15 nanoparticles as a delivery vehicle for Chlamydia trachomatis recombinant MOMP-187 peptide (United States)

    Taha, Murtada A.; Singh, Shree R.; Dennis, Vida A.


    Development of a Chlamydia trachomatis vaccine has been a formidable task partly because of an ineffective delivery system. Our laboratory has generated a recombinant peptide of C. trachomatis major outer membrane protein (MOMP) (rMOMP-187) and demonstrated that it induced at 20 μg ml-1 maximal interleukin (IL)-6 and IL-12p40 Th1 cytokines in mouse J774 macrophages. In a continuous pursuit of a C. trachomatis effective vaccine-delivery system, we encapsulated rMOMP-187 in poly(d,l-lactic-co-glycolic acid) (PLGA, 85:15 PLA/PGA ratio) to serve as a nanovaccine candidate. Physiochemical characterizations were assessed by Fourier transform-infrared spectroscopy, atomic force microscopy, Zetasizer, Zeta potential, transmission electron microcopy and differential scanning calorimetry. The encapsulated rMOMP-187 was small (˜200 nm) with an apparently smooth uniform oval structure, thermally stable (54 °C), negatively charged ( - 27.00 mV) and exhibited minimal toxicity at concentrations 95% viable cells) over a 24-72 h period. We achieved a high encapsulation efficiency of rMOMP-187 (˜98%) in PLGA, a loading peptide capacity of 2.7% and a slow release of the encapsulated peptide. Stimulation of J774 macrophages with a concentration as low as 1 μg ml -1 of encapsulated rMOMP-187 evoked high production levels of the Th1 cytokines IL-6 (874 pg ml-1) and IL-12p40 (674 pg ml-1) as well as nitric oxide (8 μM) at 24 h post-stimulation, and in a dose-response and time-kinetics manner. Our data indicate the successful encapsulation and characterization of rMOMP-187 in PLGA and, more importantly, that PLGA enhanced the capacity of the peptide to induce Th1 cytokines and NO in vitro. These findings make this nanovaccine an attractive candidate in pursuit of an efficacious vaccine against C. trachomatis.

  7. Brain-derived neurotrophic factor gene delivery in an animal model of multiple sclerosis using bone marrow stem cells as a vehicle. (United States)

    Makar, Tapas K; Bever, Christopher T; Singh, Ishwar S; Royal, Walter; Sahu, Surasri Nandan; Sura, Tushar P; Sultana, Shireen; Sura, Karna T; Patel, Niraj; Dhib-Jalbut, Suhayl; Trisler, David


    Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, is neuroprotective in animal models of neurodegenerative diseases. However, BDNF has a short half-life and its efficacy in the central nervous system (CNS), when delivered peripherally, is limited due to the blood-brain barrier (BBB). We have developed a means of delivering BDNF into the CNS using genetically engineered bone marrow stem cells (BMSCs) as a vehicle, and have explored the clinical effects of BDNF on outcomes in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). BDNF-engineered-BMSCs were transplanted (i.v.) into irradiated 2-week-old SJL/J female mice. Eight weeks after transplantation, mice were immunized with a peptide of proteolipid protein (PLP(139-151)). Mice, which had received BDNFengineered BMSCs, showed a significant delay in EAE onset and a reduction in overall clinical severity compared to mice receiving BMSC transfected with an empty vector lacking the BDNF gene. In addition, pathological examination showed that BDNF delivery reduced demyelination and increased remyelination. Inhibition of pro-inflammatory cytokines TNF-alpha and IFN-gamma and enhanced expression of the antiinflammatory cytokines IL-4, IL-10, and IL-11 were found in the CNS tissues of the BDNF transplanted group. These results support the use of BMSCs as vehicles to deliver BDNF into the CNS of EAE animals. This is a potentially novel therapeutic approach that might be used to deliver BDNF gene or genes for other therapeutic proteins into the CNS in MS or in other diseases of the CNS in which accessibility of therapeutic proteins is limited due to the BBB.

  8. Development of novel carboxymethyl cellulose/k-carrageenan blends as an enteric delivery vehicle for probiotic bacteria. (United States)

    Dafe, Alireza; Etemadi, Hossein; Zarredar, Habib; Mahdavinia, Gholam Reza


    This study reports a novel carrier based on blends of carboxymethyl cellulose (CMC) and k-carrageenan (k-Carr) for probiotic colon delivery. Lactobacillus plantarum ATCC:13643 (L. plantarum) cells were encapsulated in CMC/k-Carr blends by extrusion method. k-Carrageenan was used as a coating agent to improve encapsulation of L. plantarum cells in carboxymethyl cellulose biopolymer. K-Carrageenan and carboxymethyl cellulose were ionically cross-linked with K(+) and Ca(2+) ions, respectively. Optical and scanning electron microscopy obviously showed the random distribution of L. plantarum cells throughout the blend network. The viability of encapsulated cells in simulated gastric fluid (SGF) and bile salt solution were conducted. Results indicated that CMC/k-Carr blends could successfully protect L. plantarum cells against adverse conditions of the gastro-intestinal tract and bile salt solution. After sequential exposure to SGF for 2h almost complete death of free cells was observed. However, the number of surviving cells was 5.20 and 7.30 Log CFU/g for uncoated free CMC and CMC/k-Carr blends, respectively. Cumulatively the results of this research offer a suitable media to potentially deliver probiotics to colon site. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. In vitro antioxidant activity and in vivo antifatigue effect of layered double hydroxide nanoparticles as delivery vehicles for folic acid

    Directory of Open Access Journals (Sweden)

    Qin LL


    Full Text Available Lili Qin,1,* Wenrui Wang,2,* Songhui You,1 Jingmei Dong,1 Yunhe Zhou,1 Jibing Wang1 1Department of Physical Education, 2School of Life Science and Technology, Tongji University, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: Folic acid antioxidants were successfully intercalated into layered double hydroxides (LDH nanoparticles according to a previous method with minor modification. The resultant folic acid-LDH constructs were then characterized by X-ray powder diffraction and transmission electron microscopy. The in vitro antioxidant activities, cytotoxicity effect, and in vivo anti­fatigue were examined by a series of assays. The results showed that folic acid-LDH antioxidant system can scavenge 1,1-diphenyl-2-picrylhydrazyl and hydroxyl free radicals and chelate pro-oxidative Cu2+. The in vitro cytotoxicity assays indicated that folic acid-LDH antioxidant system had no significant cytotoxic effect or obvious toxicity to normal cells. It also prolonged the forced swimming time of the mice by 32% and 51% compared to folic acid and control groups, respectively. It had an obvious effect on decreasing the blood urea nitrogen and blood lactic acid, while increasing muscle and hepatic glycogen levels. Therefore, folic acid-LDH might be used as a novel antioxidant and antifatigue nutritional supplement. Keywords: antioxidant supplementation, free radicals, biomaterials, drug delivery

  10. Kafirin Nanoparticle-Stabilized Pickering Emulsions as Oral Delivery Vehicles: Physicochemical Stability and in Vitro Digestion Profile. (United States)

    Xiao, Jie; Li, Chao; Huang, Qingrong


    Kafirin nanoparticle-stabilized Pickering emulsions (KPEs) were used to encapsulate curcumin. The stability of KPEs under processing conditions and their protective effects against photo-oxidation of curcumin and lipid oxidation of oil in emulsions, as well as the digestion profiles in gastrointestinal tract, were investigated. KPEs were found to be more stable under acidic than basic environment, and elevated temperature induced their structural instability. The protective effect of KPEs on the chemical stability of curcumin was manifested when subjected to UV radiation as compared to other comparable formulations, such as bulk oil or Tween 80 stabilized emulsions (TEs). Meanwhile, the lipid oxidation rate was retarded in KPEs as compared to those of TEs. Due to hydrolysis of pepsin, KPEs could not survive through the gastric digestion process. After the intestinal digestion process, the extent of lipolysis of KPEs and the curcumin bioaccessibility fell between those of TEs and bulk oil. These results will fill the gap between the physicochemical properties of protein particle-based Pickering emulsions and their realistic applications in the oral delivery of functional food ingredients.

  11. Sequence-defined cMET/HGFR-targeted Polymers as Gene Delivery Vehicles for the Theranostic Sodium Iodide Symporter (NIS) Gene. (United States)

    Urnauer, Sarah; Morys, Stephan; Krhac Levacic, Ana; Müller, Andrea M; Schug, Christina; Schmohl, Kathrin A; Schwenk, Nathalie; Zach, Christian; Carlsen, Janette; Bartenstein, Peter; Wagner, Ernst; Spitzweg, Christine


    The sodium iodide symporter (NIS) as well-characterized theranostic gene represents an outstanding tool to target different cancer types allowing noninvasive imaging of functional NIS expression and therapeutic radioiodide application. Based on its overexpression on the surface of most cancer types, the cMET/hepatocyte growth factor receptor serves as ideal target for tumor-selective gene delivery. Sequence-defined polymers as nonviral gene delivery vehicles comprising polyethylene glycol (PEG) and cationic (oligoethanoamino) amide cores coupled with a cMET-binding peptide (cMBP2) were complexed with NIS-DNA and tested for receptor-specificity, transduction efficiency, and therapeutic efficacy in hepatocellular cancer cells HuH7. In vitro iodide uptake studies demonstrated high transduction efficiency and cMET-specificity of NIS-encoding polyplexes (cMBP2-PEG-Stp/NIS) compared to polyplexes without targeting ligand (Ala-PEG-Stp/NIS) and without coding DNA (cMBP2-PEG-Stp/Antisense-NIS). Tumor recruitment and vector biodistribution were investigated in vivo in a subcutaneous xenograft mouse model showing high tumor-selective iodide accumulation in cMBP2-PEG-Stp/NIS-treated mice (6.6 ± 1.6% ID/g (123)I, biological half-life 3 hours) by (123)I-scintigraphy. Therapy studies with three cycles of polyplexes and (131)I application resulted in significant delay in tumor growth and prolonged survival. These data demonstrate the enormous potential of cMET-targeted sequence-defined polymers combined with the unique theranostic function of NIS allowing for optimized transfection efficiency while eliminating toxicity.

  12. Rheological properties of soil: a review (United States)

    Zhu, Guangli; Zhu, Long; Yu, Chao


    Recently rheological methods have been applied to investigate the mechanical properties of soil micro-structure. Rheological techniques have a number of quantitative physically based measurements and offer a better understanding of how soil micro-structure behaves when subject to stress. Rheological material is refers to deformation properties similar to the solid and flow properties similar to the liquid of bound water and colloidal substances under stress. Soil rheology is divided into fluid rheology and plasticity rheology. Fluid rheology is produced by rheological material. Plasticity rheology mainly refers to the sliding and peristaltic between soil solid particles under shear stress. It is generally believed that the soft soil rheology mainly belongs to fluid rheology, while the rheology of sand and other coarse grained soil mainly belongs to plasticity rheology. Thus, rheology mechanisms of soft soil and sand are different. This paper introduces the methods of the research progress on the rheology of soil, in the soil rheological mechanism, rheological model and rheological numerical aspects of the research at home and abroad were summarized and analysed, discussed the problems existed in related research, and puts forward some suggestions for the future study on the rheology of soil.

  13. Rheology of nanofluids: a review. (United States)

    Wang, Liang; Chen, Haisheng; Witharana, Sanjeeva


    The rheological behavior of nanofluids published in recent research papers and the relevant patents are reviewed in this article. Effects of various factors such as preparation, nanoparticle and base fluid properties, concentration, temperature, surface charge, and aggregation etc. on the rheological behavior of nanofluids are discussed. Brownian motion and nanoparticle aggregation are found to be the major mechanisms for rheological properties of nanofluids compared to the micro-sized suspensions. The importance of microstructure as means of understanding the mechanisms behind the rheological and heat transfer behavior of nanofluids is also disclosed.

  14. Atoxic derivative of botulinum neurotoxin A as a prototype molecular vehicle for targeted delivery to the neuronal cytoplasm.

    Directory of Open Access Journals (Sweden)

    Edwin J Vazquez-Cintron

    Full Text Available We have previously described genetic constructs and expression systems that enable facile production of recombinant derivatives of botulinum neurotoxins (BoNTs that retain the structural and trafficking properties of wt BoNTs. In this report we describe the properties of one such derivative, BoNT/A ad, which was rendered atoxic by introducing two amino acid mutations to the light chain (LC of wt BoNT/A, and which is being developed as a molecular vehicle for delivering drugs to the neuronal cytoplasm. The neuronal binding, internalization, and intracellular trafficking of BoNT/A ad in primary hippocampal cultures was evaluated using three complimentary techniques: flow cytometry, immunohistochemistry, and Western blotting. Neuronal binding of BoNT ad was significantly increased when neurons were incubated in depolarizing medium. Flow cytometry demonstrated that BoNT/A ad internalized into neurons but not glia. After 24 hours, the majority of the neuron-bound BoNT/A ad became internalized, as determined by its resistance to pronase E-induced proteolytic degradation of proteins associated with the plasma membrane of intact cells. Significant amounts of the atoxic LC accumulated in a Triton X-100-extractable fraction of the neurons, and persisted as such for at least 11 days with no evidence of degradation. Immunocytochemical analysis demonstrated that the LC of BoNT/A ad was translocated to the neuronal cytoplasm after uptake and was specifically targeted to SNARE proteins. The atoxic LC consistently co-localized with synaptic markers SNAP-25 and VAMP-2, but was rarely co-localized with markers for early or late endosomes. These data demonstrate that BoNT/A ad mimics the trafficking properties of wt BoNT/A, confirming that our platform for designing and expressing BoNT derivatives provides an accessible system for elucidating the molecular details of BoNT trafficking, and can potentially be used to address multiple medical and biodefense needs.

  15. Hydrogen-bonding layer-by-layer-assembled biodegradable polymeric micelles as drug delivery vehicles from surfaces. (United States)

    Kim, Byeong-Su; Park, Sang Wook; Hammond, Paula T


    We present the integration of amphiphilic block copolymer micelles as nanometer-sized vehicles for hydrophobic drugs within layer-by-layer (LbL) films using alternating hydrogen bond interactions as the driving force for assembly for the first time, thus enabling the incorporation of drugs and pH-sensitive release. The film was constructed based on the hydrogen bonding between poly(acrylic acid) (PAA) as an H-bond donor and biodegradable poly(ethylene oxide)-block-poly(epsilon-caprolactone) (PEO-b-PCL) micelles as the H-bond acceptor when assembled under acidic conditions. By taking advantage of the weak interactions of the hydrogen-bonded film on hydrophobic surfaces, it is possible to generate flexible free-standing films of these materials. A free-standing micelle LbL film of (PEO-b-PCL/PAA)60 with a thickness of 3.1 microm was isolated, allowing further characterization of the bulk film properties, including morphology and phase transitions, using transmission electron microscopy and differential scanning calorimetry. Because of the sensitive nature of the hydrogen bonding employed to build the multilayers, the film can be rapidly deconstructed to release micelles upon exposure to physiological conditions. However, we could also successfully control the rate of film deconstruction by cross-linking carboxylic acid groups in PAA through thermally induced anhydride linkages, which retard the drug release to the surrounding medium to enable sustained release over multiple days. To demonstrate efficacy in delivering active therapeutics, in vitro Kirby-Bauer assays against Staphylococcus aureus were used to illustrate that the drug-loaded micelle LbL film can release significant amounts of an active antibacterial drug, triclosan, to inhibit the growth of bacteria. Because the micellar encapsulation of hydrophobic therapeutics does not require specific chemical interactions, we believe this noncovalent approach provides a new route to integrating active small

  16. Solid lipid nanoparticles as a vehicle for brain-targeted drug delivery: two new strategies of functionalization with apolipoprotein E (United States)

    Rute Neves, Ana; Fontes Queiroz, Joana; Weksler, Babette; Romero, Ignacio A.; Couraud, Pierre-Olivier; Reis, Salette


    Nanotechnology can be an important tool to improve the permeability of some drugs for the blood-brain barrier. In this work we created a new system to enter the brain by functionalizing solid lipid nanoparticles with apolipoprotein E, aiming to enhance their binding to low-density lipoprotein receptors on the blood-brain barrier endothelial cells. Solid lipid nanoparticles were successfully functionalized with apolipoprotein E using two distinct strategies that took advantage of the strong interaction between biotin and avidin. Transmission electron microscopy images revealed spherical nanoparticles, and dynamic light scattering gave a Z-average under 200 nm, a polydispersity index below 0.2, and a zeta potential between -10 mV and -15 mV. The functionalization of solid lipid nanoparticles with apolipoprotein E was demonstrated by infrared spectroscopy and fluorimetric assays. In vitro cytotoxic effects were evaluated by MTT and LDH assays in the human cerebral microvascular endothelial cells (hCMEC/D3) cell line, a human blood-brain barrier model, and revealed no toxicity up to 1.5 mg ml-1 over 4 h of incubation. The brain permeability was evaluated in transwell devices with hCMEC/D3 monolayers, and a 1.5-fold increment in barrier transit was verified for functionalized nanoparticles when compared with non-functionalized ones. The results suggested that these novel apolipoprotein E-functionalized nanoparticles resulted in dynamic stable systems capable of being used for an improved and specialized brain delivery of drugs through the blood-brain barrier.

  17. Taboo search algorithm of split delivery vehicle routing problem%需求可拆分车辆路径问题的禁忌搜索算法

    Institute of Scientific and Technical Information of China (English)

    孟凡超; 陆志强; 孙小明


    为解决实际配送运输中的车辆路径问题(Vehicle Routing Problem,VRP),通过改进传统的数学模型,解除每个客户需求只能由1辆车配送的约束,建立改进的可拆分车辆路径问题(SplitDelivery VRP,SDVRP)数学模型,并利用禁忌搜索算法(Taboo Search Algorithm,TSA)进行求解.在TSA的设计中,根据SDVRP模型的特点对初始解、邻域搜索和解的评价等进行特殊处理.算例表明,该模型不仅可以解决VRP模型中不允许配送点需求量超出装载量的限制,而且通过相应配送点需求量的拆分和重新组合,可节省车辆数目、缩短路线长度、提高车辆装载率.

  18. Self-aggregated nanoparticles of linoleic acid-modified glycol chitosan conjugate as delivery vehicles for paclitaxel: preparation, characterization and evaluation. (United States)

    Yu, Jingmou; Liu, Yonghua; Zhang, Lei; Zhao, Jianguo; Ren, Jin; Zhang, Lifang; Jin, Yi


    A series of linoleic acid-modified glycol chitosan (LAGC) conjugates were synthesized and characterized by FTIR and (1)H NMR. The effect of the amount of linoleic acid (LA) on the physicochemical properties of LAGC conjugates was investigated. The mean diameters of three LAGC nanoparticles determined by dynamic light scattering ranged from 204 to 289 nm. The critical aggregation concentration values of LAGC conjugates in aqueous solution were 0.0148, 0.0348, and 0.0807 mg/ml, respectively. Paclitaxel (PTX) was physically loaded into the LAGC nanoparticles by a dialysis method. The drug loading content and encapsulation efficiency of PTX-loaded LAGC (PTX-LAGC) nanoparticles increased with an increasing ratio of the hydrophobic LA to hydrophilic glycol chitosan in the conjugates. PTX-LAGC nanoparticles were almost spherical in shape observed by transmission electron microscopy. In vitro release revealed that PTX release from the nanoparticles was reduced as the LA substitution degree of LAGC conjugates increased. Compared with the commercial formulation Taxol, PTX-LAGC-1 nanoparticles exhibited comparable cellular uptake and cytotoxicity against HepG2 cells in vitro. Importantly, PTX-LAGC-1 nanoparticles demonstrated the stronger antitumor efficacy against hepatic H22 tumor-bearing mice than Taxol (p delivery vehicles for tumor therapy.

  19. DNA-based aptamer fails as a simultaneous cancer targeting agent and drug delivery vehicle for a phenanthroline-based platinum(II) complex. (United States)

    McGinely, Nicola L; Plumb, Jane A; Wheate, Nial J


    The sgc8c aptamer is a 41-base DNA oligonucleotide that binds to leukaemia cells with high affinity and specificity. In this work we examined the utility of this aptamer as both a delivery vehicle and an active targeting agent for an inert platinum complex [(1,10-phenathroline)(ethylenediamine)platinum(II)](2+). The aptamer forms a stem-and-loop confirmation as determined by circular dichroism. This conformation is adopted in both water and phosphate buffered saline solutions. The metal complex binds through intercalation into the aptamer's double helical stem with a binding constant of approximately 4.3 × 10(4) M(-1). Binding of the metal complex to the aptamer had a significant effect on the aptamer's global conformation, and increased its melting temperature by 28°C possibly through lengthening and stiffening of the aptamer stem. The effect of the aptamer on the metal complex's cytotoxicity and cellular uptake was determined using in vitro assays with the target leukaemia cell line CCRF-CEM and the off-target ovarian cancer cell lines A2780 and A2780cp70. The aptamer has little inherent cytotoxicity and when used to deliver the metal complex results in a significant decrease in the metal complex's cytotoxicity and uptake. The reason(s) for the poor uptake and activity may be due to the change in aptamer conformation which affects its ability to recognise leukaemia cells.

  20. Self-assembly of core-polyethylene glycol-lipid shell (CPLS) nanoparticles and their potential as drug delivery vehicles (United States)

    Shen, Zhiqiang; Loe, David T.; Awino, Joseph K.; Kröger, Martin; Rouge, Jessica L.; Li, Ying


    potential of simulation-driven approaches for guiding the design of more efficient nanomaterial delivery platforms.Herein a new multifunctional formulation, referred to as a core-polyethylene glycol-lipid shell (CPLS) nanoparticle, has been proposed and studied in silico via large scale coarse-grained molecular dynamics simulations. A PEGylated core with surface tethered polyethylene glycol (PEG) chains is used as the starting configuration, where the free ends of the PEG chains are covalently bonded with lipid molecules (lipid heads). A complete lipid bilayer is formed at the surface of the PEGylated particle core upon addition of free lipids, driven by the hydrophobic properties of the lipid tails, leading to the formation of a CPLS nanoparticle. The self-assembly process is found to be sensitive to the grafting density and molecular weight of the tethered PEG chains, as well as the amount of free lipids added. At low grafting densities the assembly of CPLS nanoparticles cannot be accomplished. As demonstrated by simulations, a lipid bud/vesicle can be formed on the surface when an excess amount of free lipids is added at high grafting density. Therefore, the CPLS nanoparticles can only be formed under appropriate conditions of both PEG and free lipids. The CPLS nanoparticle has been recognized to be able to store a large quantity of water molecules, particularly with high molecular weight of PEG chains, indicating its capacity for carrying hydrophilic molecules such as therapeutic biomolecules or imaging agents. Under identical size and surface chemistry conditions of a liposome, it has been observed that the CPLS particle can be more efficiently wrapped by the lipid membrane, indicating its potential for a greater efficiency in delivering its hydrophilic cargo. As a proof-of-concept, the experimental realization of CPLS nanoparticles is explicitly demonstrated in this study. To test the capacity of the CPLS to store small molecule cargo a hydrophilic dye was

  1. 5th European Rheology Conference

    CERN Document Server


    Global sustainable development of the world economy requires better understanding and utilization of natural recourses. In this endeavor rheology has an indispensable role. The Rheology Conferences are therefore always an important event for science and technology. The Fifth European Rheology Conference, held from September 6 to 11 in the Portoro-z, Slovenia, will be the first AlI-European rheology meeting after the formal constitution of the European Society ofRheology. As such it will be a special historical event. At this meeting the European Society of Rheology will introduce the Weissenberg Medal, to be bestowed every four years to an individual for hislhers contribution to the field of Rheology. The recipient ofthe first award will be professor G. Marrucci ofthe Universita degli Studi di Napoli, Italy. Two mini Symposia will be part of the Conference. The first, on Industrial Rheology, will commemorate the late professor G. Astarita. The second will honor the eightieth birthday of professor N.W. Tschoeg...

  2. Molecule-Based Rheology Switching

    NARCIS (Netherlands)

    Paulusse, Jos M.J.; Sijbesma, Rint P.


    Sound-activated switching: The rheological behavior of fluids can be affected by external stimuli, as demonstrated by electrochemically and photochemically induced changes in viscosity and sol–gel transitions. Recently, ultrasound has emerged as a novel rheology switch for supramolecular polymers an

  3. Transdermal drug delivery using microemulsion and aqueous systems: influence of skin storage conditions on the in vitro permeability of diclofenac from aqueous vehicle systems. (United States)

    Sintov, Amnon C; Botner, Shafir


    The objective of this study was to evaluate the transdermal delivery potential of diclofenac-containing microemulsion system in vivo and in vitro. It was found that the transdermal administration of the microemulsion to rats resulted in 8-fold higher drug plasma levels than those obtained after application of Voltaren Emulgel. After s.c. administration (3.5 mg/kg), the plasma levels of diclofenac reached a peak of 0.94 microg/ml at t=1 h and decreased rapidly to 0.19 microg/ml at t=6 h, while transdermal administration of the drug in microemulsion maintained constant levels of 0.7-0.9 microg/ml for at least 8 h. The transdermal fluxes of diclofenac were measured in vitro using skin excised from different animal species. In three rodent species, penetration fluxes of 53.35+/-8.19 (furry mouse), 31.70+/-3.83 (hairless mouse), 31.66+/-4.45 (rat), and 22.89+/-6.23 microg/cm(2)/h (hairless guinea pig) were obtained following the application of the microemulsion. These fluxes were significantly higher than those obtained by application of the drug in aqueous solution. In contrast to these results, a 'flip-flop' phenomenon was observed when frozen porcine skin (but not fresh skin) was significantly more permeable to diclofenac-in-water than to the drug-in-microemulsion. In fact, the drug penetration from the microemulsion was not affected by the skin storage conditions, but it was increased when an aqueous solution was applied. However, this unusual phenomenon observed in non-freshly used porcine skin places a question mark on its relevancy for in vitro penetration studies involving aqueous vehicle systems.

  4. Etoposide-loaded biodegradable amphiphilic methoxy (poly ethylene glycol) and poly (epsilon caprolactone) copolymeric micelles as drug delivery vehicle for cancer therapy. (United States)

    Mohanty, Anjan K; Dilnawaz, Fahima; Mohanty, Chandana; Sahoo, Sanjeeb K


    Amphiphilic diblock copolymers composed of methoxy poly ethylene glycol (MePEG) and poly epsilon caprolactone (PCL) were synthesized for the formation of micelles by ring opening mechanism using stannous octoate as a catalyst. The effects of the molecular weight of MePEG and the copolymer ratio on the properties of micelles were investigated by Nuclear Magnetic Resonance ((1)H-NMR), Fourier Transform Infrared Spectroscopy (FT-IR), and Gel Permeation Chromatography (GPC). The diblock copolymers were self-assembled to form micelles and their hydrophobic core was used for the encapsulation of the anti-cancer drug (etoposide) in aqueous solution. The sizes of micelles were less than 250 nm with a narrow size distribution with monodispersed unimodal pattern. Differential Scanning Calorimetric (DSC) thermogram was done for etoposide-loaded micelles to understand the crystalline nature of the drug after entrapment. A drug loading capacity up to 60% (w/w) with an entrapment efficiency of 68% was achieved as determined by reverse phase high performance liquid chromatography (RP-HPLC). In vitro release kinetics showed a biphasic release pattern of etoposide for 2 weeks. The cytotoxic efficacy of the etoposide-loaded micelles demonstrated greater anti-proliferative activity (IC(50) = 1.1 microg/ml) as compared to native drug (IC(50) = 6.3 microg/ml) in pancreatic cancer cell line MIA-PaCa-2. Thus, etoposide-loaded MePEG/PCL block copolymeric micelles can be used as an efficient drug delivery vehicle for pancreatic cancer therapy.

  5. Unifying suspension and granular rheology. (United States)

    Boyer, François; Guazzelli, Élisabeth; Pouliquen, Olivier


    Using an original pressure-imposed shear cell, we study the rheology of dense suspensions. We show that they exhibit a viscoplastic behavior similarly to granular media successfully described by a frictional rheology and fully characterized by the evolution of the friction coefficient μ and the volume fraction ϕ with a dimensionless viscous number I(v). Dense suspension and granular media are thus unified under a common framework. These results are shown to be compatible with classical empirical models of suspension rheology and provide a clear determination of constitutive laws close to the jamming transition.

  6. Correlation of rheological parameters in maternal and fetal blood at term. (United States)

    Csorba, Roland; Soliman, Amr A; Wieg, Christian; Tsikouras, Panagiotis; Rath, Werner; von Tempelhoff, Georg-Friedrich


    An association between maternal and fetal blood rheology has not yet been investigated nor is it known whether and to what extent fetal blood rheology may be affected by maternal conditions. At delivery, blood was drawn from the cubital vein of 4985 consecutive mothers and from the umbilical cord during birth for determination of blood rheological parameters (erythrocyte aggregation stasis [E0], low shear [E1], plasma viscosity [Pv]) in addition to hemoglobin (Hb) values and hematocrit (Hct). Maternal and newborn Pv (r = 0.2; p delivery time-points refers to a more gaining protein synthesis by the fetal liver and thus maturity of the fetus. Iron supplementation as well as smoking during pregnancy is associated with a relative hyper-viscosity in the fetus at delivery.

  7. Rheological characterization of dental waxes


    Zhang, Kehao


    Objectives The purpose of this study was to evaluate the rheological behaviour of new experimental dental waxes in dependent on temperature. Material and method Seven experimental dental waxes, provided by Dentaurum GmbH, were tested. No.018 was chosen as a control. Rheological experiments were performed at different temperatures using a Paar Physica Rheometer UDS200 equiped with a parallel plate cell. The temperature was regulated with a Peltier system (TEK130P) and a thermostat un...

  8. Influence of MR damper modeling on vehicle dynamics (United States)

    de-J Lozoya-Santos, Jorge; Morales-Menendez, Ruben; Ramirez-Mendoza, Ricardo A.; Vivas-Lopez, Carlos A.


    The influence of magneto-rheological damper modeling in vehicle dynamics analysis is studied. Several tests using CarSim™ compare a four-corner controlled semi-active suspension for two different magneto-rheological damper models. The magneto-rheological damper characteristics were identified from experimental data. A model-free controller discards the influence of control and emphasizes the compliance of the magneto-rheological damper model; the characteristics of the vehicle index performance considered were comfort, road holding, handling, roll and suspension deflection. The comparison for magneto-rheological damper dynamics and semi-active suspension covers the automotive bandwidth. The results show that high precision of a magneto-rheological damper model as an isolated feature is not enough. The magneto-rheological damper model, as a component of a vehicle suspension, needs to simulate with passive precision and variable damping forces. The findings exhibit the requisite of accurate models for evaluation of semi-active control systems in classic tests. The lack of the friction component in a magneto-rheological damper model leads to an overestimation in handling and stability.

  9. Bee colony optimization algorithm for split delivery vehicle routing problem%需求可拆分车辆路径问题的蜂群优化算法

    Institute of Scientific and Technical Information of China (English)

    汪婷婷; 倪郁东; 何文玲


    In this paper ,the split delivery vehicle routing problem is researched and the mathematical optimization model w hich seeks the shortest distance to meet the delivery requirements is constructed . T he model releases the constraint that only one vehicle can be used to meet the delivery requirement for one customer .A new bee colony optimization(BCO) algorithm is proposed based on the improve-ment of the reaction threshold and the value of stimulatory signal .The experimental result proves the feasibility of the algorithm ,and also highlights the strong optimization ability of BCO algorithm by comparison with other typical algorithms .%文章研究了需求可拆分的车辆路径问题,通过解除传统车辆路径问题中每个任务点需求只能由1辆车满足的约束,建立了寻求满足配送要求最短行驶距离的数学优化模型,在改进反应阈值和刺激信号值的基础上提出了一种新型蜂群优化算法。仿真实验结果验证了算法的可行性,并通过与其他典型算法对比凸显了该算法较强的寻优能力。

  10. Biodegradable Eri silk nanoparticles as a delivery vehicle for bovine lactoferrin against MDA-MB-231 and MCF-7 breast cancer cells

    Directory of Open Access Journals (Sweden)

    Roy K


    Full Text Available Kislay Roy,1,* Yogesh S Patel,1,* Rupinder K Kanwar,1 Rangam Rajkhowa,2 Xungai Wang,2 Jagat R Kanwar1 1Nanomedicine-Laboratory of Immunology and Molecular Biomedical Research (NLIMBR, Centre for Molecular and Medical Research (C-MMR, School of Medicine (SoM, Faculty of Health, 2Institute for Frontier Materials (IFM, Deakin University, Waurn Ponds, VIC, Australia *These authors contributed equally to this work Abstract: This study used the Eri silk nanoparticles (NPs for delivering apo-bovine lactoferrin (Apo-bLf (~2% iron saturated and Fe-bLf (100% iron saturated in MDA-MB-231 and MCF-7 breast cancer cell lines. Apo-bLf and Fe-bLf-loaded Eri silk NPs with sizes between 200 and 300 nm (±10 nm showed a significant internalization within 4 hours in MDA-MB-231 cells when compared to MCF-7 cells. The ex vivo loop assay with chitosan-coated Fe-bLf-loaded silk NPs was able to substantiate its future use in oral administration and showed the maximum absorption within 24 hours by ileum. Both Apo-bLf and Fe-bLf induced increase in expression of low-density lipoprotein receptor-related protein 1 and lactoferrin receptor in epidermal growth factor (EGFR-positive MDA-MB-231 cells, while transferrin receptor (TfR and TfR2 in MCF-7 cells facilitated the receptor-mediated endocytosis of NPs. Controlled and sustained release of both bLf from silk NPs was shown to induce more cancer-specific cytotoxicity in MDA-MB-231 and MCF-7 cells compared to normal MCF-10A cells. Due to higher degree of internalization, the extent of cytotoxicity and apoptosis was significantly higher in MDA-MB-231 (EGFR+ cells when compared to MCF-7 (EGFR- cells. The expression of a prominent anti-cancer target, survivin, was found to be downregulated at both gene and protein levels. Taken together, all the observations suggest the potential use of Eri silk NPs as a delivery vehicle for an anti-cancer milk protein, and indicate bLf for the treatment of breast cancer. Keywords: breast

  11. Topical delivery of clobetasol propionate loaded microemulsion based gel for effective treatment of vitiligo--part II: rheological characterization and in vivo assessment through dermatopharmacokinetic and pilot clinical studies. (United States)

    Patel, Hetal K; Barot, Bhavesh S; Parejiya, Punit B; Shelat, Pragna K; Shukla, Arunkumar


    Vitiligo is a non contagious acquired pigmentation disorder with limited treatment possibilities. Clobetasol propionate (CP) is the drug-of-choice for vitiligo which suppresses the immune system by reducing immunoglobulin action and causes the restoration of melanocytes leading to repigmentation of skin. However, despite being effective, its low and variable bioavailability prompt for development of novel carrier that could effectively target CP to site of action without producing undesirable side-effects. Low solubility of CP in subsequent poor in vivo bioavailability was overcome by formulating microemulsion based gel of CP (MBC) which would enhance the percutaneous transport of CP into and across the skin barrier. Comprehensive characterization of MBC was carried out for viscosity, gel strength and rheological behavior. In vitro studies revealed much higher drug release, skin penetration and enhanced skin accumulation as compared to control (Cream of CP). In vitro and in vivo occlusion studies demonstrated similar occlusiveness for MBC and control. MBC exhibited 3.16 times higher stratum corneum CP levels compared to control. Visualization of cutaneous uptake in vivo using laser scanning microscopy confirmed targeting of CP to epidermis and dermis. Dermatopharmacokinetic studies of MBC showed enhanced drug deposition of CP in skin layers. MBC was assessed for in vivo efficacy by single blind randomized pilot clinical study. The efficacy was assessed by vitiligo area scoring index (VASI) method. After completion of trial, repigmentation of vitiligo patches in patients were evaluated and scored. MBC was superior in terms of faster repigmentation and efficacy when compared with control (p valuevitiligo patients.

  12. Hardware and software package for search, detection and first aid means delivery in rough terrain on basis of a three rotor unmanned aerial vehicle

    Directory of Open Access Journals (Sweden)

    Sergii FIRSOV


    Full Text Available The unmanned aerial vehicles are used for dangerous tasks solution. The search and detection of injured in rough terrain is one of them. Thus, vertical take-off unmanned aerial vehicles are of a special interest. A hardware and software package for the task solving is proposed in the article.

  13. Rheology of fractal networks

    CERN Document Server

    Patricio, Pedro; Duarte, Jorge; Januario, Cristina


    We investigate the rheology of a fractal network, in the framework of the linear theory of viscoelasticity. We identify each segment of the network with a simple Kelvin-Voigt element, with a well defined equilibrium length. The final structure retains the elastic characteristics of a solid or a gel. By considering a very simple regular self-similar structure of segments in series and in parallel, in 1, 2 or 3 dimensions, we are able to express the viscoelasticity of the network as an effective generalised Kelvin-Voigt model with a power law spectrum of retardation times, $\\phi\\sim\\tau^{\\alpha-1}$. We relate the parameter $\\alpha$ with the fractal dimension of the gel. In some regimes ($0<\\alpha<1$), we recover the weak power law behaviours of the elastic and viscous moduli with the angular frequencies, $G'\\sim G''\\sim w^\\alpha$, that occur in a variety of soft materials, including living cells. In other regimes, we find different and interesting power laws for $G'$ and $G''$.

  14. Surface rheology and interface stability.

    Energy Technology Data Exchange (ETDEWEB)

    Yaklin, Melissa A.; Cote, Raymond O.; Moffat, Harry K.; Grillet, Anne Mary; Walker, Lynn; Koehler, Timothy P.; Reichert, Matthew D. (Carnegie Mellon University, Pittsburgh, PA); Castaneda, Jaime N.; Mondy, Lisa Ann; Brooks, Carlton, F.


    We have developed a mature laboratory at Sandia to measure interfacial rheology, using a combination of home-built, commercially available, and customized commercial tools. An Interfacial Shear Rheometer (KSV ISR-400) was modified and the software improved to increase sensitivity and reliability. Another shear rheometer, a TA Instruments AR-G2, was equipped with a du Nouey ring, bicone geometry, and a double wall ring. These interfacial attachments were compared to each other and to the ISR. The best results with the AR-G2 were obtained with the du Nouey ring. A Micro-Interfacial Rheometer (MIR) was developed in house to obtain the much higher sensitivity given by a smaller probe. However, it was found to be difficult to apply this technique for highly elastic surfaces. Interfaces also exhibit dilatational rheology when the interface changes area, such as occurs when bubbles grow or shrink. To measure this rheological response we developed a Surface Dilatational Rheometer (SDR), in which changes in surface tension with surface area are measured during the oscillation of the volume of a pendant drop or bubble. All instruments were tested with various surfactant solutions to determine the limitations of each. In addition, foaming capability and foam stability were tested and compared with the rheology data. It was found that there was no clear correlation of surface rheology with foaming/defoaming with different types of surfactants, but, within a family of surfactants, rheology could predict the foam stability. Diffusion of surfactants to the interface and the behavior of polyelectrolytes were two subjects studied with the new equipment. Finally, surface rheological terms were added to a finite element Navier-Stokes solver and preliminary testing of the code completed. Recommendations for improved implementation were given. When completed we plan to use the computations to better interpret the experimental data and account for the effects of the underlying bulk

  15. A new underwater operating swimmer delivery vehicle(SDV) for divers and payload%一种用于蛙人或有效载荷的水下新型运载器

    Institute of Scientific and Technical Information of China (English)

    钟宏伟; 韩雪; 周辉


    阐述一种新型多功能单兵作战的水下小型蛙人运载器,该装备是由潜艇鱼雷发射管或水面舰艇释放的一种新型单兵装备.武装蛙人以匍匐的形式封闭在运载器内,通过运载器内操控台上的信息及按钮选择执行作战任务,完成任务后运载器可回收.它是一种远程运载蛙人或有效载荷的特种运载器、探测器,具有较远运送特种作战蛙人、较远距离实施攻击、较广泛作战用途及较高智能程度、较低费效比的特点,能对敌方目标形成较大的威胁.同时也是蛙人撤离和逃生的一种手段,是海军不对称作战的有力武器.通过对此型单兵运载器的研究,对我国新型蛙人运载器的设计理念起到一定的启发作用.%This article demonstrated a new multi-functioning individual underwater swimmer delivery vehicle,which belongs to a new individual combat weapon that can be launched from both submarine torpedo tube and surface ship.The combat swimmer crawls in the sealed vehicle,operating missions through the information and buttons selected on the control console in the vehicle,and the vehicle can be recovered after the task was finished.It is a special vehicle or detector for transporting swimmer or payload for a long distance with such characteristics as transporting swimmer and attacking target for a long distance,multi-function operating,high intelligence,low cost-benefit ratio and greatly threatening the enemy.At the same time,it is also a way of evacuation and escaping for the swimmer as well as a useful weapon of navy asymmetric operations.So,the design idea of our new swimmer delivery vehicle can be enlightened a lot from the research of it.

  16. Rheology of Model Dough Formulation (United States)

    Desai, Kiran; Lele, Smita; Lele, Ashish


    Dough is generally considered a viscoelastic material, and its elasticity is attributed to the hydrated gluten matrix. Since starch is a major constituent of flour (˜70 wt% on dry basis) we may expect it to contribute to dough rheology in a non-trivial manner. Considering dough to belong to the generic class of soft solid materials, we use the Strain-Rate Frequency Superposition (SRFS) technique to study rheology of various model dough compositions in which the starch/gluten ratio is systematically varied from 100/0 to 0/100. We find that for compositions containing 0-25% gluten the SRFS superposition principle works well, while for compositions containing greater than 25% gluten the quality of SRFS mastercurves deteriorates gradually. Thus we propose that starch particles contribute substantially to the rheology of dough containing up to 25% gluten.

  17. Rheology of Biopolymer Solutions and Gels


    David R. Picout; Ross-Murphy, Simon B.


    Rheological techniques and methods have been employed for many decades in the characterization of polymers. Originally developed and used on synthetic polymers, rheology has then found much interest in the field of natural (bio) polymers. This review concentrates on introducing the fundamentals of rheology and on discussing the rheological aspects and properties of the two major classes of biopolymers: polysaccharides and proteins. An overview of both their solution properties (dilute to semi...

  18. Rheology of Biopolymer Solutions and Gels

    Directory of Open Access Journals (Sweden)

    David R. Picout


    Full Text Available Rheological techniques and methods have been employed for many decades in the characterization of polymers. Originally developed and used on synthetic polymers, rheology has then found much interest in the field of natural (bio polymers. This review concentrates on introducing the fundamentals of rheology and on discussing the rheological aspects and properties of the two major classes of biopolymers: polysaccharides and proteins. An overview of both their solution properties (dilute to semi-dilute and gel properties is described.

  19. Rheological Properties of Aging Thermosensitive Suspensions

    NARCIS (Netherlands)

    Purnomo, E.H; van den Ende, Henricus T.M.; Mellema, J.; Mugele, Friedrich Gunther


    Aging observed in soft glassy materials inherently affects the rheological properties of these systems and has been described by the soft glassy rheology (SGR) model [S. M. Fielding et al., J. Rheol. 44, 323 (2000)]. In this paper, we report the measured linear rheological behavior of

  20. Optimal Routing of Cigarette Delivery Vehicle Based on Genetic Algorithm%基于遗传算法的烟草配送车路径优化问题

    Institute of Scientific and Technical Information of China (English)



    On the basis of establishing an optimized model for optimal routing of cigarette delivery vehicle problem, the paper uses techniques such as roulette wheel selection, partially matched crossover and self adaptation for fitness function, designs a genotic algorithm based on natural numbers. At the end of the paper make some experimental calculations using this algorithm. The experimental calculations results demonstrate that the optimal or nearly optimal solutions to the Cigarette Delivery Vehicle routing problem can be easily obtained by using genetic algorithm.%在建立烟草配送车路径优化问题模型的基础上,采用轮盘赌复制法、部分匹配交叉算法、和适应度函数自适应调整等技术,设计了基于自然数编码的遗传算法,最后以这种方法进行了实验计算,通过计算结果表明,用遗传算法进行烟草车配送路径优化,可以方便有效地求得问题的最优解或近似最优解.

  1. 带时间窗的快递物流车辆调度模型及应用%Application of Express Delivery Vehicle Dispatching Model with Time Window

    Institute of Scientific and Technical Information of China (English)

    王洁; 江洋; 王莉; 熊焱


    In this paper, on the basis of an analysis of the operational characteristics of the express delivery vehicles, we established a two-way heterogeneous vehicle dispatching model with time window that integrated the delivery and collection processes, then accordingly designed a C-W saving algorithm that allowed multiple instances of service to one customer, and at the end, validated the model established through a case study.%在分析快递物流企业运作特点的基础上,建立了带时间窗的多车型集派送、收集于一体的双向车辆调度问题模型,针对该模型设计了可对同一客户多次服务的C-W节约算法.通过实例计算结果分析表明,该模型能体现快递物流企业车辆调度特点且设计的算法易于计算机实现,效果较为理想.

  2. Effects of stress conditions on rheological properties of granular soil in large triaxial rheology laboratory tests

    Institute of Scientific and Technical Information of China (English)

    陈晓斌; 张家生; 刘宝琛; 唐孟雄


    In order to study the rheological properties of red stone granular soil,a series of rheological experiments were executed on large tri-axial rheological apparatus.Under 100,200 and 300 kPa confining stress conditions,the rheological tests were carried out.These experiment results showed that the stress conditions,especially the stress level were the critical influencing factors of the rheological deformation properties.Under the low stress level(S=0.1),the granular soil showed the elastic properties,and there was no obvious rheological deformation.Under the middle stress level(0.2rheological properties.However,under the high stress level(S>0.8) creep curves showed the non-linear viscous plastic rheological properties.Especially,under the stress level of S=1.0,the accelerated rheological phase of creep curves occurred at early time with a trend of failure.The stress level had obvious effects on the final rheological deformation of the soil sample,and the final rheological deformation increments nonlinearly increased with stress level.The final rheological deformation increment and step was little under low stress level,while it became large under high stress level,which showed the nonlinearly rheological properties of the granular soil.The confining pressure also had direct effects on final rheological deformation,and the final rheological deformation linearly increased with confining pressure increments.

  3. Simple rheology of mixed proteins (United States)

    Mixing different proteins to form strong gel networks for food applications may create synergistic increases in viscoelasticity that cannot be achieved with a single protein. In this study, small amplitude oscillatory shear analyses were used to investigate the rheology of calcium caseinate (CC), e...

  4. Rheological measurements on artifical muds

    NARCIS (Netherlands)

    De Wit, P.J.


    The rheological behaviour of three artificial muds was determined using a rotational viscometer. First some characteristics of the viscometer used were rneasured. For want of an appropriate calibration tluid, the viscosity of demineralized water was determined. The result agreed very well with what


    Directory of Open Access Journals (Sweden)

    V. V. Artemchuk


    Full Text Available The issues related to renewal of worn-out parts of a rolling stock with the layered coatings are considered in the article. In developing a mathematical model of wearing a multilayer material as an object of rheology certain assumptions, which enable using the methods of mechanics and mechanics of continuous medium, are done.

  6. Probing the interaction of nanoparticles with mucin for drug delivery applications using dynamic light scattering. (United States)

    Griffiths, Peter Charles; Cattoz, Beatrice; Ibrahim, Mervat Shafik; Anuonye, Josephine Chibuzor


    Drug delivery via the eye, nose, gastrointestinal tract and lung is of great interest as they represent patient-compliant and facile methods to administer drugs. However, for a drug to reach the systemic circulation it must penetrate the "mucus barrier". An understanding of the characteristics of the mucus barrier is therefore important in the design of mucus penetrating drug delivery vehicles e.g. nanoparticles. Here, a range of nanoparticles - silica, aluminium coated silica, poly (lactic-co-glycolic acid) (PLGA) and PEGylated PLGA - each with known but different physicochemical characteristics were examined in the presence of mucin to identify those characteristics that engender nanoparticle/mucin interactions and thus, to define "design rules" for mucus penetrating (nano)particles (MPP), at least in terms of the surface characteristics of charge and hydrophilicity. Dynamic light scattering (DLS) and rheology have been used to assess the interaction between such nanoparticles and mucin. It was found that negatively charged and hydrophilic nanoparticles do not exhibit an interaction with mucin whereas positively charged and hydrophobic nanoparticles show a strong interaction. Surface grafted poly (ethylene glycol) (PEG) chains significantly reduced this interaction. This study clearly demonstrates that the established colloid science techniques of DLS and rheology are very powerful screening tools to probe nanoparticle/mucin interactions.

  7. Research on Multi-type Vehicle Scheduling Problem in Urban Logistics with Dynamic Delivery Cost and Fuzzy Delivery Mileage%具有模糊行程的城市物流动态费用多车型车辆调度问题研究

    Institute of Scientific and Technical Information of China (English)

    卢冰原; 程八一


    针对城市物流配送中广泛存在的多车型问题,以及由于交通路况等因素导致的配送行程模糊化现象,给出了一种基于梯形模糊数的,以最小化行程费用为目标的具有模糊行程的动态费用多车型车辆调度问题模型.在问题求解方面,针对基本粒子群算法容易陷入局部最优的情况,引入混沌局部搜索策略,给出了一种基于混沌优化技术的混合粒子群算法.仿真实验表明,该算法具有可行性和有效性.%For the multi-type vehicle scheduling problem in city distribution, and fuzzy delivery mileage problem caused by traffic and road factors, based on trapezoidal fuzzy number, a multi-type vehicle scheduling problem (MVSP) model having dynamic delivery cost and fuzzy delivery mileage for minimized delivery cost is introduced firstly. After that, aiming at the problems of easily getting into the local optimum of basic particle swarm optimization (PSO) algorithm, a hybrid PSO algorithm based on chaotic local optimizer is proposed for the MVSP problem above,which help the algorithm to improve its resulting precision and convergence rate. At last, through the analysis of the simulating experiment results, the feasibility and efficency of the algorithm are approved.

  8. The Vehicle Routing Problem with Simultaneous Pickup and Delivery Considering Customer Satisfaction%考虑客户满意度的同时收发车辆路径问题

    Institute of Scientific and Technical Information of China (English)



    当客户要求车辆一次性完成发送以及收集货物的任务时, 只需考虑车辆的路径安排即可.但若客户进一步提出在时间窗内完成的话,就必须考虑客户的等待时间--客户的满意度的衡量标准,等待时间越短满意度越高.因此问题的目标为最小化车辆路径总长度、最小化所有客户等待时间之和.本文通过加权转变为单目标函数,由最邻近法及最廉价插入法得到初始解后经过禁忌搜索算法可得到改进算法,解并通过实例对不同权参数的情况进行了比较.%When customers require the vehicles to pickup and delivery goods simultaneous, we just consider how to arrange the path of every vehicle.However, if costomers further propose the vehicles to complete within time windows, costumers' waiting time which is regarded as the criterion of customers satisfaction must be considered, that is, the shorter, the higher the satisfaction.Therefore the goal is to minimize the total length of vehicles' paths, and to minimize the sum of all customers' waiting time.In this paper, combining into a single objective function by weight, initial solution, obtained by the nearest neighbor method and the cheapest insertion method, can be improved by tabu search algorithm.Finally solutions of different parameters are compared.

  9. Cumulative Vehicle Routing Problems


    Kara, &#;mdat; Kara, Bahar Yeti&#;; Yeti&#;, M. Kadri


    This paper proposes a new objective function and corresponding formulations for the vehicle routing problem. The new cost function defined as the product of the distance of the arc and the flow on that arc. We call a vehicle routing problem with this new objective function as the Cumulative Vehicle Routing Problem (CumVRP). Integer programming formulations with O(n2) binary variables and O(n2) constraints are developed for both collection and delivery cases. We show that the CumVRP is a gener...

  10. 车载Ad Hoc网络中基于移动网关的数据传输%MGF: Mobile Gateway Based Forwarding for Infrastructure-to-Vehicle Data Delivery in Vehicular Ad Hoc Networks

    Institute of Scientific and Technical Information of China (English)

    陈丽; 李治军; 姜守旭; 冯诚


    由于车载Ad hoc网络拓扑的动态变化及车载节点的快速移动,应用现有传输方法在其上进行Internet接入点向移动车辆(Infrastructure-to-Vehicle,I2V)数据传输时成功率较低,而且传输延迟高、延迟抖动大.为了解决这一问题,文中利用公交车路线固定、运行特征可预测、节点及线路分布稠密等特性,将公交车作为移动网关( Mobile Gateway,MG),提出了一种新的基于MG转发的I2V数据传输方法(Mobile Gateway based Forwarding,MGF).文中首先将公路网模型化为状态-空间图,再运用马尔可夫决策方法建立了一种基于MG转发的I2V数据传输优化模型,然后通过对模型求解得出I2V数据传输的最优转发决策,最优转发决策指的就是每个状态下对应的最优动作序列,最后在目的车辆行驶轨迹上选取满足传输成功率阈值,并使I2V传输延迟最小的路口节点作为数据包与目的车辆的最优汇聚节点,即目标节点.应用MGF方法,MG节点将以最优概率转发序列向目标节点转发数据包.文中利用模拟平台对MGF方法的传输性能进行了评估,结果表明该方法在满足传输成功率阈值前提下,能够获得最小传输延迟期望.理论分析同样也证明了该方法的有效性.%The highly dynamic topology and the rapid movement of destination node pose special challenges to Infrastructure-to-Vehicle (I2V) data delivery in Vehicular Ad Hoc Networks (VANET). Current data delivery methods are with the strong delay, the large jitter of delay and low delivery ratio for I2V data delivery. The paper investigates how to effectively utilize the prominent characteristic of buses, and proposes Mobile Gateway (MG) based Forwarding (MGF) that buses are installed as MG to forward data packet. To solve the problem that the paper models road network as a probabilistic state-space graph, in which applies the value iteration algorithm for the markov decision processing model to derive the

  11. Disruption management of the vehicle routing problem with vehicle breakdown

    DEFF Research Database (Denmark)

    Mu, Q; Fu, Z; Lysgaard, Jens


    This paper introduces a new class of problem, the disrupted vehicle routing problem (VRP), which deals with the disruptions that occur at the execution stage of a VRP plan. The paper then focuses on one type of such problem, in which a vehicle breaks down during the delivery and a new routing...

  12. Emissions from light and medium goods vehicles in Denmark

    DEFF Research Database (Denmark)

    Jørgensen, Kaj


    The article analyses atmospheric pollution of light goods vehicles (i.e. freight vehicles lighter than 6 tonnes) and medium goods vehicles (i.e. 6-24 t delivery trucks) in Denmark, and evaluated the scope for emission reductions. Light goods vehicles are very inefficient vehicles, and moreover ha...

  13. Investigating the rheological properties of native plant latex. (United States)

    Bauer, Georg; Friedrich, Christian; Gillig, Carina; Vollrath, Fritz; Speck, Thomas; Holland, Chris


    Plant latex, the source of natural rubber, has been of interest to mankind for millennia, with much of the research on its rheological (flow) properties focused towards industrial application. However, little is known regarding the rheology of the native material as produced by the plant, a key factor in determining latex's biological functions. In this study, we outline a method for rheological comparison between native latices that requires a minimum of preparatory steps. Our approach provides quantitative insights into the coagulation mechanisms of Euphorbia and Ficus latex allowing interpretation within a comparative evolutionary framework. Our findings reveal that in laboratory conditions both latices behave like non-Newtonian materials with the coagulation of Euphorbia latex being mediated by a slow evaporative process (more than 60 min), whereas Ficus appears to use additional biochemical components to increase the rate of coagulation (more than 30 min). Based on these results, we propose two different primary defensive roles for latex in these plants: the delivery of anti-herbivory compounds (Euphorbia) and rapid wound healing (Ficus).


    Energy Technology Data Exchange (ETDEWEB)

    Hansen, E.


    The overall objective of the EM-31 Rheological Modifiers and Wetting Agents program is to utilize commercially available rheology modifiers to increase the solids fraction of radioactive sludge based waste streams, resulting in an increase in throughput and decreasing the overall processing time. The program first investigates the impact of rheology modifiers on slurry simulants and then utilizes the most effective rheology modifiers on radioactive slurries. The work presented in this document covers the initial investigation of rheology modifier testing with simulants. This task is supported by both the Savannah River National Laboratory (SRNL) and Pacific Northwest National Laboratory (PNNL). The SRNL EM-31 task, for this year, was to investigate the use of rheology modifiers on simulant Defense Waste Processing Facility (DWPF) melter feeds. The task is to determine, based on the impact of the rheology modifier, if there are rheology modifiers that could reduce the water content of the slurry going to the DWPF melter, hence increasing the melt rate by decreasing the water loading. The rheology modifier in essence would allow a higher solids content slurry to have the same type of rheology or pumpability of a lower solids slurry. The modifiers selected in this report were determined based on previous modifiers used in high level waste melter feed simulants, on-going testing performed by counterparts at PNNL, and experiences gain through use of modifiers in other Department of Energy (DOE) processes such as grout processing. There were 12 rheology modifiers selected for testing, covering both organic and inorganic types and they were tested at four different concentrations for a given melter feed. Five different DWPF melter feeds were available and there was adequate material in one of the melter feeds to increase the solids concentration, resulting in a total of six simulants for testing. The mass of melter feed available in each simulant was not adequate for

  15. Molecular Rheology of Complex Fluids

    DEFF Research Database (Denmark)

    Huang, Qian; Rasmussen, Henrik Koblitz

    The processing of polymer materials is highly governed by its rheology, and influences the properties of the final product. For example, a recurring problem is instability in extrusion that leads to imperfect plastic parts. The ability to predict and control the rheological behavior of polymer......–state viscosity between melts and solutions is still an open question. Branched polymer melts have more complex molecular structures. A stress maximum during the start–up of uniaxial extensional flow was reported in 1979 for a low–density polyethylene (LDPE) melt. Subsequently observations of a steady stress......) linear polystyrene melts and solutions; 2) the bidisperse and polydisperse linear polystyrene melts; 3) the NMMD branched polystyrene melts; and 4) the polydisperse branched polyethylene melts. The experimental results are also compared with some developing theoretical models. Finally, to ensure...

  16. Acrylated chitosan for mucoadhesive drug delivery systems. (United States)

    Shitrit, Yulia; Bianco-Peled, Havazelet


    A new mucoadhesive polymer was synthesized by conjugating chitosan to poly(ethylene glycol)diacrylate (PEGDA) via the Michael type reaction. The product was characterized using NMR. Higher PEGDA grafting efficacy was observed with low molecular weight PEGDA (0.7kDa), compared to long 10kDa PEGDA. The acrylation percentage was calculated based on the reaction of ninhydrin with chitosan, and supported the qualitative NMR findings. The adhesive properties were studied by tensile test and rotating system involving detachment of polymer tablets from a fresh intestine sample. Chitosan modified with high molecular weight PEGDA presented improvement in mucoadhesive properties compared to both non-modified and thiolated chitosan. On the molecular level, rheology measurements of polymer/mucin mixtures provided additional evidence of strong interaction between modified chitosan and mucin glycoproteins. This new polymer shows promise as a useful polymeric carrier matrix for delivery systems, which could provide prolonged residence time of the vehicle on the mucosa surface. Copyright © 2016 Elsevier B.V. All rights reserved.



    Camelia Vizireanu; Aurelia Ionescu; Daniela Istrati; Felicia Dima


    The increased social and economic importance of ready–made food production, together with the complexity of production technology, processing, handling and acceptance of these fragile and perishable products requires extensive knowledge of their physical properties. Viscoelastic properties play an important role in the handling and quality attributes of creams.Our study was to investigate the rheological properties of different confectionary creams, by scanning the field of shear rates at con...

  18. Implementing Vehicle Routing Algorithms (United States)


    Multiple Depot Vehicle Dispatch Problem," presented at the URSA/TIMS meeting San Juan, Puerto Rico, Oct. 1974. 28. Gillett, B., and Miller, L., " A Heuristic Algorithm for...45. Lam, T., "Comments on a Heuristic Algorithm for the Multiple Terminal Delivery Problem," Transportation Science, Vol. 4, No. 4, Nov. 1970, p. 403

  19. Transient rheology of stimuli responsive hydrogels: Integrating microrheology and microfluidics (United States)

    Sato, Jun

    Stimuli-responsive hydrogels have diverse potential applications in the field of drug delivery, tissue engineering, agriculture, cosmetics, gene therapy, and as sensors and actuators due to their unique responsiveness to external signals, such as pH, temperature, and ionic strength. Understanding the responsiveness of hydrogel structure and rheology to these stimuli is essential for designing materials with desirable performance. However, no instrumentation and well-defined methodology are available to characterize the structural and rheological responses to rapid solvent changes. In this thesis, a new microrheology set-up is described, which allows us to quantitatively measure the transient rheological properties and microstructure of a variety of solvent-responsive complex fluids. The device was constructed by integrating particle tracking microrheology and microfluidics and offers unique experimental capabilities for performing solvent-reponse measurements on soft fragile materials without applying external shear forces. Transient analysis methods to quantitatively obtain rheological properties were also constructed, and guidelines for the trade-off between statistical validity and temporal resolution were developed to accurately capture physical transitions. Employing the new device and methodology, we successfully quantified the transient rheological and microstructural responses during gel formation and break-up, and viscosity changes of solvent-responsive complex fluids. The analysis method was expanded for heterogeneous samples, incorporating methods to quantify the microrheology of samples with broad distributions of individual particle dynamics. Transient microrheology measurements of fragile, heterogeneous, self-assembled block copolypeptide hydrogels revealed that solvent exchange via convective mixing and dialysis can lead to significantly different gel properties and that commonly applied sample preparation protocols for the characterization of soft

  20. Vehicle Routing with Uncertain Demand

    NARCIS (Netherlands)

    R. Spliet (Remy)


    textabstractIn distribution networks a supplier transports goods from a distribution center to customers by means of vehicles with limited capacity. Drivers will drive routes on which they visit multiple customers to make deliveries. Typically, deliveries are made regularly and a fixed schedule is m

  1. Simultaneous delivery and pickup vehicle routing problem with three-dimension ;loading constraints%同时取送货的三维装载约束下车辆路径问题

    Institute of Scientific and Technical Information of China (English)

    彭碧涛; 周世平


    同时取货和送货的三维装载约束下车辆路径问题(3L-VRPSDP)是经典车辆路径问题(VRP)的一个扩展,在3L-VRPSDP中,顾客可能要求同时取货和送货,而且货物装载要考虑其三维大小、先进后出、底面支撑等装载特性。针对这类问题,提出了基于左底优先和最大接触面优先的装载算法,在装载时要考虑其配送特征;在此基础上,设计了对应的禁忌搜索算法对初始结果进行优化,通过实验验证了算法的有效性。%The Simultaneous Delivery and Pickup Vehicle Routing Problem with Three-Dimension Loading Constraints (3L-VRPSDP)is a variant of the classical Vehicle Routing Problem(VRP)where clients may require simultaneous pickups and deliveries, at the same time, cargo must consider its three dimensional size, first in last out, bottom support constraints. Considering the distribution characteristics, the loading algorithms based on Left Bottom(LB)and Maximum Contact Area (MCA)are proposed, and the corresponding tabu search algorithms are designed. Experiments are given to prove the validity of the algorithms.

  2. 非病毒载体在siRNA体内递送中的应用%Application of non-viral vehicles in siRNA delivery in vivo

    Institute of Scientific and Technical Information of China (English)

    姜扩; 裘秀春


    RNAi is a specific gene-silencing mechanism triggered by siRNA. Since its discovery, the RNAi technology has rapidly developed as a new strategy for drug target validation and the study of functional genomics, and it is currently being evaluated as a potential therapy for diseases of a genetic etiology. However, due to the instable physicochemical properties of siRNAs in vivo, the major impediment of RNAi application is the delivery vehicles. Therefore, the research of efficient siRNA delivery for siRNA protection, cellular uptake, correct intracellular localization and endosomal release, combination with high biocompatibility, devoid of nonspecific knockdown and toxic side effects is crucial for the success of RNAi-based therapeutics. In this review, the recent advances of siRNA non-viral vehicles are summarized.%RNAi是一种由siRNA触发的特异基因沉默机制.自其发现以来,RNAi技术迅速发展为药物靶标确认和功能基因组学研究的新策略,并有望成为一种疾病基因治疗学方法.然而,由于siRNA体内不稳定的理化性质,递送siRNA成为RNAi发展的最大障碍.因此研发能够保护siRNA、促进细胞吸收、正确细胞定位和包内体逃逸,结合具有高生物相容性与减少非特异沉默和毒性反应的体内递送系统是RNAi成功用于临床治疗的关键.本文就体内非病毒载体方式递送siRNA的研究进展进行综述.

  3. Extracellular vesicles for drug delivery

    NARCIS (Netherlands)

    Vader, Pieter; Mol, Emma A; Pasterkamp, Gerard; Schiffelers, Raymond M

    Extracellular vesicles (EVs) are cell-derived membrane vesicles, and represent an endogenous mechanism for intercellular communication. Since the discovery that EVs are capable of functionally transferring biological information, the potential use of EVs as drug delivery vehicles has gained

  4. Rheology v.3 theory and applications

    CERN Document Server

    Eirich, Frederick


    Rheology: Theory and Applications, Volume 3 is a collection of articles contributed by experts in the field of rheology - the science of deformation and flow. This volume is composed of specialized chapters on the application of normal coordinate analysis to the theory of high polymers; principles of rheometry; and the rheology of cross-linked plastics, poly electrolytes, latexes, inks, pastes, and clay. Also included are a series of technological articles on lubrication, spinning, molding, extrusion, and adhesion and a survey of the general features of industrial rheology. Materials scientist

  5. State of the art of control schemes for smart systems featuring magneto-rheological materials (United States)

    Choi, Seung-Bok; Li, Weihua; Yu, Miao; Du, Haiping; Fu, Jie; Do, Phu Xuan


    This review presents various control strategies for application systems utilizing smart magneto-rheological fluid (MRF) and magneto-rheological elastomers (MRE). It is well known that both MRF and MRE are actively studied and applied to many practical systems such as vehicle dampers. The mandatory requirements for successful applications of MRF and MRE include several factors: advanced material properties, optimal mechanisms, suitable modeling, and appropriate control schemes. Among these requirements, the use of an appropriate control scheme is a crucial factor since it is the final action stage of the application systems to achieve the desired output responses. There are numerous different control strategies which have been applied to many different application systems of MRF and MRE, summarized in this review. In the literature review, advantages and disadvantages of each control scheme are discussed so that potential researchers can develop more effective strategies to achieve higher control performance of many application systems utilizing magneto-rheological materials.

  6. Rheological properties of magneto-responsive copolymer gels

    NARCIS (Netherlands)

    An, H.


    New magneto rheological systems that respond mechanically to external homogeneous magnetic fields, namely, physically cross-linked magneto rheological (MR) gels, were synthesized and investigated. Various aspects of the rheological behavior were considered such as linear viscoelastic response for va

  7. Vehicle to Vehicle Services

    DEFF Research Database (Denmark)

    Brønsted, Jeppe Rørbæk


    , mobility, and availability of services. The dissertation consists of two parts. Part I gives an overview of service oriented architecture for pervasive computing systems and describes the contributions of the publications listed in part II. We investigate architecture for vehicular technology applications......As computing devices, sensors, and actuators pervade our surroundings, new applications emerge with accompanying research challenges. In the transportation domain vehicles are being linked by wireless communication and equipped with an array of sensors and actuators that make is possible to provide...... location aware infotainment, increase safety, and lessen environmental strain. This dissertation is about service oriented architecture for pervasive computing with an emphasis on vehicle to vehicle applications. If devices are exposed as services, applications can be created by composing a set of services...

  8. Lipid-based liquid crystalline nanoparticles as oral drug delivery vehicles for poorly water-soluble drugs: cellular interaction and in vivo absorption

    Directory of Open Access Journals (Sweden)

    Zeng N


    Full Text Available Ni Zeng,1,3,* Xiaoling Gao,2,* Quanyin Hu,1 Qingxiang Song,2 Huimin Xia,1 Zhongyang Liu,1 Guangzhi Gu,1 Mengyin Jiang,1,4 Zhiqing Pang,1 Hongzhuan Chen,2 Jun Chen,1 Liang Fang3 1Key Laboratory of Smart Drug Delivery, Ministry of Education and PLA, School of Pharmacy, Fudan University, Shanghai, 2Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiaotong University School of Medicine, Shanghai, 3Department of Pharmaceutical Science, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning, 4School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, Shandong People's Republic of China, *These authors contributed equally to this workBackground: Lipid-based liquid crystalline nanoparticles (LCNPs have attracted growing interest as novel drug-delivery systems for improving the bioavailability of both hydrophilic and hydrophobic drugs. However, their cellular interaction and in vivo behavior have not been fully developed and characterized.Methods: In this study, self-assembled LCNPs prepared from soy phosphatidylcholine and glycerol dioleate were developed as a platform for oral delivery of paclitaxel. The particle size of empty LCNPs and paclitaxel-loaded LCNPs was around 80 nm. The phase behavior of the liquid crystalline matrix was characterized using crossed polarized light microscopy and small-angle X-ray scattering, and showed both reversed cubic and hexagonal phase in the liquid crystalline matrix. Transmission electron microscopy and cryofield emission scanning electron microscopy analysis revealed an inner winding water channel in LCNPs and a "ball-like"/"hexagonal" morphology.Results: Cellular uptake of LCNPs in Caco-2 cells was found to be concentration-dependent and time-dependent, with involvement of both clathrin and caveolae/lipid raft-mediated endocytosis. Under confocal laser scanning microscopy, soy phosphatidylcholine was observed to segregate from the internalized LCNPs and

  9. Cytochrome c end-capped mesoporous silica nanoparticles as redox-responsive drug delivery vehicles for liver tumor-targeted triplex therapy in vitro and in vivo. (United States)

    Zhang, Beilu; Luo, Zhong; Liu, Junjie; Ding, Xingwei; Li, Jinghua; Cai, Kaiyong


    To develop carriers for efficient anti-cancer drug delivery with reduced side effects, a biocompatible and redox-responsive nanocontainer based on mesoporous silica nanoparticles (MSNs) for tumor-targeted triplex therapy was reported in this study. The nanocontainer was fabricated by immobilizing cytochrome c (CytC) onto the MSNs as sealing agent via intermediate linkers of disulfide bonds for redox-responsive intracellular drug delivery. AS1411 aptamer was further tailored onto MSNs for cell/tumor targeting. The successful construction of redox- responsive MSNs was confirmed by BET/BJH analysis, transmission electron microscopy, Fourier transform infrared spectroscopy, fluorescence spectroscopy and thermogravimetric analysis (TGA), respectively. Detailed investigations demonstrated that anticancer drug of doxorubicin (DOX) loaded nanocontainer could be triggered by reductant (e.g. glutathione) within cellular microenvironment and release DOX to induce tumor cell apoptosis in vitro. More importantly, the nanocontainer displayed great potential for tumor targeting and achieved triplex therapy effects on the tumor inhibition in vivo through the loading DOX, gatekeeper of CytC and AS1411 aptamer, which were reflected by the change of tumor size, TUNEL staining and HE staining assays.

  10. Rheology of unstable mineral emulsions

    Directory of Open Access Journals (Sweden)

    Sokolović Dunja S.


    Full Text Available In this paper, the rheology of mineral oils and their unstable water emulsion were investigated. The oil samples were domestic crude oil UA, its fractions UA1, UA4 and blend semi-product UP1, while the concentration of oil in water emulsions was in the range from 1 up to 30%. The results were analyzed based on shear stress. The oil samples UA, UA1 and UP1 are Newtonian fluids, while UA4 is pseudoplastic fluid. The samples UA and UA4 show higher value of shear stress (83.75 Pa, 297 Pa, then other two samples UA1 and UP1 (18.41 Pa, 17.52 Pa. Rheology of investigated oils due to its complex chemical composition should be analyzed as a simultaneous effect of all their components. Therefore, structural composition of the oils was determined, namely content of paraffins, naphthenes, aromatics and asphaltenes. All samples contain paraffins, naphthenes and aromatics but only oils UA and UA4 contain asphaltenes as well. All investigated emulsions except 30% EUA4 are Newtonian fluids. The EUA4 30% emulsion shows pseudoplastic behaviour, and it is the only 30% emulsion among investigated ones that achieves lower shear stress then its oil. The characteristics of oil samples that could have an influence on their properties and their emulsion rheology, were determined. These characteristics are: neutralization number, interfacial tension, dielectric constant, and emulsivity. Oil samples UA and UA4 have significantly higher values of neutralization number, dielectric constants, and emulsivity. The sample UA has the lowest value of interface tension and the greatest emulsivity, indicating that this oil, among all investigated, has the highest preference for building emulsion. This could be the reason why 20% and 30% emulsions of the oil UA achieve the highest shear stress among all investigated emulsions.

  11. Cataclastic rheology of carbonate rocks

    Institute of Scientific and Technical Information of China (English)

    LU Xiancai; SUN Yan; SHU Liangshu; GU Lianxing; GUO Jichun; ZHU Wenbin


    Based on the knowledge of the shallow-level mylonitization of detrital rocks and intrusive rocks, the poorly-known cataclastic rheology of carbonate rocks is discussed comprehensively in this paper. The cases taken from eastern China are analyzed in various aspects including ductile-brittle fault zone, rock texture and structure, clastomylonite layer, leucocratic stress minerals, and frictional dynamometamorphism. It is proposed that the cataclastic flow structure represented by clastomylonite texture is a cooling pattern of flow assemblage characterized by cooling metamorphism, cooling mylonite and cooling stress minerals. Such a pattern is formed generally in mildly reducing physicochemical environments, and is commonly related to regional tectonism and mesothermal and epithermal mineralization.

  12. Rheological behaviour of lahar flow (United States)

    Lafarge, N.; Chambon, G.; Thouret, J. C.; Laigle, D.


    Lahars are mixtures of water and debris flowing down the flanks of volcanoes. These flows generally occur after heavy rainfalls and carry sediments deposited by volcanic eruptions. They are among the most destructive volcanic phenomena, and were responsible, in the 20th century, for 40% of the fatalities associated with volcanic eruptions worldwide. However, the mechanical behaviour and the propagation of these particular debris flows still remain poorly understood. In the frame of the research project Laharisk, Mount Semeru in Java (Indonesia) was chosen as a test site to monitor lahar activity and flows properties owing to the frequent occurrence of lahars on its flanks during the monsoon rainy period. Two observation stations, situated 510 m apart, were installed in the Curah Lengkong Valley on the southeast flank of Semeru volcano. The relatively straight and box-shaped channel between the two stations represents a natural flume well suited to study the hydraulics of the flows. Both stations are equipped with video cameras, pore-pressure and load sensors, AFM geophones, and one broad-band seismometer to measure the evolution over time of lahar flow height, speed, and discharge. Bucket samples are also directly taken in the flows at regular time-intervals in order to provide sediment concentration and grain-size distribution. The rheological behaviour of the material is studied through laboratory vane tests at constant imposed shear rate conducted on the fine-sized fraction (independent of the shear rate. In addition, the friction coefficient increases with sediment concentration. At the scale of the flow, the rheology of the material can also be investigated through the relationship between flow height and discharge in control sections. The obtained relationship has the form of a power law, and is also indicative of a frictional mechanical behaviour. Here also, the concentration appears as an important parameter controlling the rheological behavior of flow

  13. Stability and recovery of DIFICID(®) (Fidaxomicin) 200-mg crushed tablet preparations from three delivery vehicles, and administration of an aqueous dispersion via nasogastric tube. (United States)

    Tousseeva, Anna; Jackson, J Derek; Redell, Mark; Henry, Teresa; Hui, Michael; Capurso, Shelley; DeRyke, C Andrew


    Fidaxomicin is approved for the treatment of adults with Clostridium difficile-associated diarrhea, many of whom have difficulty swallowing an intact tablet. The study objective was to evaluate the stability and recovery of crushed DIFICID(®) (fidaxomicin) 200-mg tablets dispersed in water, applesauce, or Ensure(®) brand liquid nutritional supplement, and to determine the recovery of fidaxomicin from the administration of an aqueous dispersion of a crushed DIFICID(®) tablet through a nasogastric (NG) tube. DIFICID(®) tablets were crushed and dispersed in water, applesauce, or Ensure(®). The stability and recovery of fidaxomicin were evaluated over 24 h in these vehicles. In a separate experiment, the ability to recover a full dose of fidaxomicin when administering as an aqueous dispersion through an NG tube was assessed. When DIFICID(®) tablets were crushed and dispersed in water, the active ingredient, fidaxomicin, was stable for up to 2 h at room temperature. Additionally, it was stable for up to 24 h in dispersions with applesauce or Ensure(®). Recovery of fidaxomicin after crushing and dispersing in any of the three vehicles studied ranged from 95 to 108 %, which is within the normal range of individual tablet variability. When crushed, dispersed in water, and administered through an NG tube, the average recovery of fidaxomicin was 96 %. Stability and recovery of fidaxomicin were confirmed when DIFICID(®) tablets were crushed and dispersed in water, applesauce, or Ensure(®). In addition, administration of an aqueous dispersion of a crushed tablet through an NG tube is supported by acceptable recovery of fidaxomicin.

  14. The Impact of Blood Rheology on Drug Transport in Stented Arteries: Steady Simulations (United States)

    Vijayaratnam, Pujith R. S.; O’Brien, Caroline C.; Reizes, John A.; Barber, Tracie J.; Edelman, Elazer R.


    Background and Methods It is important to ensure that blood flow is modelled accurately in numerical studies of arteries featuring drug-eluting stents due to the significant proportion of drug transport from the stent into the arterial wall which is flow-mediated. Modelling blood is complicated, however, by variations in blood rheological behaviour between individuals, blood’s complex near-wall behaviour, and the large number of rheological models which have been proposed. In this study, a series of steady-state computational fluid dynamics analyses were performed in which the traditional Newtonian model was compared against a range of non-Newtonian models. The impact of these rheological models was elucidated through comparisons of haemodynamic flow details and drug transport behaviour at various blood flow rates. Results Recirculation lengths were found to reduce by as much as 24% with the inclusion of a non-Newtonian rheological model. Another model possessing the viscosity and density of blood plasma was also implemented to account for near-wall red blood cell losses and yielded recirculation length increases of up to 59%. However, the deviation from the average drug concentration in the tissue obtained with the Newtonian model was observed to be less than 5% in all cases except one. Despite the small sensitivity to the effects of viscosity variations, the spatial distribution of drug matter in the tissue was found to be significantly affected by rheological model selection. Conclusions/Significance These results may be used to guide blood rheological model selection in future numerical studies. The clinical significance of these results is that they convey that the magnitude of drug uptake in stent-based drug delivery is relatively insensitive to individual variations in blood rheology. Furthermore, the finding that flow separation regions formed downstream of the stent struts diminish drug uptake may be of interest to device designers. PMID:26066041

  15. Using Greener Gels to Explore Rheology (United States)

    Garrett, Brendan; Matharu, Avtar S.; Hurst, Glenn A.


    A laboratory experiment was developed to investigate the rheological properties of a green calcium-cross-linked alginate gel as an alternative to the traditional borax-cross-linked poly(vinyl alcohol) gel. As borax is suspected of damaging fertility and the unborn child, a safe, green alternative is necessary. The rheological properties of a…

  16. Supramolecular assembly and rheology in food systems

    NARCIS (Netherlands)

    Linden, van der E.; Sagis, L.M.C.; Venema, P.


    We address some recent progress in describing rheological responxe in the linear regime in terms of structural morphology and interactions between mesostructures. As one of the examples we use gels composed of protein fibrils. We subsequently address rheological response in the non-linear regime in

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

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


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

  18. Sugar-decorated mesoporous silica nanoparticles as delivery vehicles for the poorly soluble drug celastrol enables targeted induction of apoptosis in cancer cells. (United States)

    Niemelä, Erik; Desai, Diti; Nkizinkiko, Yves; Eriksson, John E; Rosenholm, Jessica M


    Cancerous cells have a rapid metabolism by which they take up sugars, such as glucose, at significantly higher rates than normal cells. Celastrol is a traditional herbal medicine known for its anti-inflammatory and anti-cancer activities. The poor aqueous solubility and lack of target selectivity of celastrol result in low therapeutic concentration of the drug reaching subcellular compartments of the target tissue, making it an interesting candidate for nanoparticulate delivery. The goal of this study was to utilize glucose as an affinity ligand decorated on mesoporous silica nanoparticles (MSNs), with the aim of delivering these celastrol-loaded MSNs with high specificity to cancer cells and inducing minimal off-target effects in healthy cells. MSNs were thus functionalized with sugar moieties by two different routes, either by conjugation directly to the MSN surface or mediated by a hyperbranched poly(ethylene imine), PEI layer; the latter to increase the cellular uptake by providing an overall positive surface charge as well as to increase the reaction sites for sugar conjugation. The effect of surface functionalization on the target-specific efficacy of the particles was assessed by analyzing the uptake in HeLa and A549 cells as cancer cell models, as compared to mouse embryonic fibroblasts (MEF) as a representative for normal cells. To this end a comprehensive analysis strategy was employed, including flow cytometry, confocal microscopy, and spectrophotometry. When the apoptotic effect of celastrol was evaluated, the anti-cancer activity of celastrol was shown to be significantly enhanced when it was loaded into the specifically designed MSNs. The particles themselves did not induce any toxicity, and normal cells displayed minimal off-target effects. In summary, we show that glucose-functionalized MSNs can be used as efficient carriers for targeted celastrol delivery to achieve specific induction of apoptosis in cancer cells. Copyright © 2015 Elsevier B

  19. Hydrogen vehicle fueling station

    Energy Technology Data Exchange (ETDEWEB)

    Daney, D.E.; Edeskuty, F.J.; Daugherty, M.A. [Los Alamos National Lab., NM (United States)] [and others


    Hydrogen fueling stations are an essential element in the practical application of hydrogen as a vehicle fuel, and a number of issues such as safety, efficiency, design, and operating procedures can only be accurately addressed by a practical demonstration. Regardless of whether the vehicle is powered by an internal combustion engine or fuel cell, or whether the vehicle has a liquid or gaseous fuel tank, the fueling station is a critical technology which is the link between the local storage facility and the vehicle. Because most merchant hydrogen delivered in the US today (and in the near future) is in liquid form due to the overall economics of production and delivery, we believe a practical refueling station should be designed to receive liquid. Systems studies confirm this assumption for stations fueling up to about 300 vehicles. Our fueling station, aimed at refueling fleet vehicles, will receive hydrogen as a liquid and dispense it as either liquid, high pressure gas, or low pressure gas. Thus, it can refuel any of the three types of tanks proposed for hydrogen-powered vehicles -- liquid, gaseous, or hydride. The paper discusses the fueling station design. Results of a numerical model of liquid hydrogen vehicle tank filling, with emphasis on no vent filling, are presented to illustrate the usefulness of the model as a design tool. Results of our vehicle performance model illustrate our thesis that it is too early to judge what the preferred method of on-board vehicle fuel storage will be in practice -- thus our decision to accommodate all three methods.


    Directory of Open Access Journals (Sweden)

    Camelia Vizireanu


    Full Text Available The increased social and economic importance of ready–made food production, together with the complexity of production technology, processing, handling and acceptance of these fragile and perishable products requires extensive knowledge of their physical properties. Viscoelastic properties play an important role in the handling and quality attributes of creams.Our study was to investigate the rheological properties of different confectionary creams, by scanning the field of shear rates at constant temperature and frequency, angular frequency scanning at small deformations and quantification of rheological changes during application of deformation voltages. The creams tested were made in the laboratory using specific concentrates as fine powders, marketed by the company “Dr. Oetker” compared with similar creams based on traditional recipes and techniques. Following the researches conducted we could conclude that both traditional creams and the instant ones are semi fluid food products with pseudoplastic and thixotropic shear flow behavior, with structural viscosity. Instant and traditional creams behaved as physical gels with links susceptible to destruction, when subjected to deformation forces.

  1. Rheological evolution of subducting slabs (United States)

    Hirth, G.


    The mechanical behavior of subducting lithosphere depends on both the rheological evolution of the slab and how the slab is modified prior to subduction. Geophysical data demonstrate that the combination of thermal evolution and deformation lead to alteration of the slab at both mid-ocean ridges and the outer rise of subduction zones. In addition, the locations of earthquakes in these locations are generally consistent with both extrapolation of laboratory data that constrain the depth to the brittle-plastic transition, and deformation mechanisms inferred from microstructural analysis of mantle rocks recovered from the oceanic lithosphere. However, the frictional properties of both mantle aggregates and their alteration products suggest that linking the location of lithospheric earthquakes to regions that become hydrothermally altered is not straightforward. Furthermore, the inferred link between the location of intermediate-depth seismicity and the conditions of dehydration reactions is challenged by laboratory studies on dehydration embrittlement. In this presentation, I will introduce these apparent discrepancies; provide some possible resolutions for them based on scaling of laboratory data and discuss the implications for how an integrated understanding of slab rheology informs our understanding of the mechanical and geochemical evolution of the slab.

  2. Microgravity Foam Structure and Rheology (United States)

    Durian, Douglas J.


    To exploit rheological and multiple-light scattering techniques, and ultimately microgravity conditions, in order to quantify and elucidate the unusual elastic character of foams in terms of their underlying microscopic structure and dynamics. Special interest is in determining how this elastic character vanishes, i.e. how the foam melts into a simple viscous liquid, as a function of both increasing liquid content and shear strain rate. The unusual elastic character of foams will be quantified macroscopically by measurement of the shear stress as a function of static shear strain, shear strain rate, and time following a step strain; such data will be analyzed in terms of a yield stress, a static shear modulus, and dynamical time scales. Microscopic information about bubble packing and rearrangement dynamics, from which these macroscopic non-Newtonian properties presumably arise, will be obtained non-invasively by novel multiple-light scattering diagnostics such as Diffusing-Wave Spectroscopy (DWS). Quantitative trends with materials parameters, such as average bubble size, and liquid content, will be sought in order to elucidate the fundamental connection between the microscopic structure and dynamics and the macroscopic rheology.

  3. Rheology as a Tool to Predict the Release of Alpha-Lipoic Acid from Emulsions Used for the Prevention of Skin Aging. (United States)

    Isaac, Vera Lucia Borges; Chiari-Andréo, Bruna Galdorfini; Marto, Joana Marques; Moraes, Jemima Daniela Dias; Leone, Beatriz Alves; Corrêa, Marcos Antonio; Ribeiro, Helena Margarida


    The availability of an active substance through the skin depends basically on two consecutive steps: the release of this substance from the vehicle and its subsequent permeation through the skin. Hence, studies on the specific properties of vehicles, such as their rheological behavior, are of great interest in the field of dermatological products. Recent studies have shown the influence of the rheological features of a vehicle on the release of drugs and active compounds from the formulation. In this context, the aim of this study was to evaluate the influence of the rheological features of two different emulsion formulations on the release of alpha-lipoic acid. Alpha-lipoic acid (ALA) was chosen for this study because of its antioxidant characteristics, which could be useful for the prevention of skin diseases and aging. The rheological and mechanical behavior and the in vitro release profile were assayed. The results showed that rheological features, such as viscosity, thixotropy, and compliance, strongly influenced the release of ALA from the emulsion and that the presence of a hydrophilic polymer in one of the emulsions was an important factor affecting the rheology and, therefore, the release of ALA.

  4. Parallel Hybrid Vehicle Optimal Storage System (United States)

    Bloomfield, Aaron P.


    A paper reports the results of a Hybrid Diesel Vehicle Project focused on a parallel hybrid configuration suitable for diesel-powered, medium-sized, commercial vehicles commonly used for parcel delivery and shuttle buses, as the missions of these types of vehicles require frequent stops. During these stops, electric hybridization can effectively recover the vehicle's kinetic energy during the deceleration, store it onboard, and then use that energy to assist in the subsequent acceleration.

  5. 同时送取货车辆路径问题算法研究综述%Algorithm review of vehicle routing problem with simultaneous delivery and pickup

    Institute of Scientific and Technical Information of China (English)

    王科峰; 叶春明; 李永林


    针对同时送取货车辆路径问题的研究算法进行了评述.将该问题的求解方法分为精确算法、构造型启发式、现代启发式以及并行算法四个大类.从算法的原理、性能、适用环境,以及算法之间差异性等方面对各类算法进行了较为全面的介绍.最后,说明了VRPSDP算法研究在节点具有双重需求车辆路径问题理论研究方面的意义,并提出未来VRPSDP算法研究的两个发展方向,即适合多处理器上运行的并行现代启发式算法,以及有效的混合算法如量子行为粒子群算法.%This paper gave a review about the algorithms for the vehicle routing problem with simultaneous delivery and pickup (VRPSDP). It divided the solving methods into four main classes; exact algorithm, constructive heuristics algorithm, meta-heuristics algorithm, and parallel algorithm. It also gave the detail introductions of the algorithms from the principle, performance, application environment, and the differences between them. In the end, it introduced the significance of the algorithm research of VRPSDP in the theory development of the vehicle routing problem with node having double demands. After that, it proposed two research directions in the future, which were parallel metaheuristics based on multiple processors, and the effec-tive hybrid algorithm such as quantum-behaved particle swarm optimization.

  6. A Model and Algorithm to Solve Vehicle Routing Problem with Split Delivery%需求可分的车辆路径问题模型与算法

    Institute of Scientific and Technical Information of China (English)

    谢秉磊; 胡小明; 张一喆


    需求可分的车辆路径问题(SDVRP)无论是从运输距离还是派车数量上,都可进一步优化传统的车辆路径问题.为了降低SDVRP的求解难度,本文在分析最优解性质的基础上,加强模型的约束条件,将原模型转变为等价的改进SDVRP,并在使用蚂蚁算法求解改进SDVRP模型的过程中,采用开发新路径和2-opt相结合的方法,以避免出现迭代停滞的现象.实验表明,算法计算结果稳定,最差解与最好解的偏差仅为1.80%.%Vehicle routing model with split delivery( SDVRP) can optimize further traditional vehicle routing problem in both transportation distance and the number of dispatching vehicle. To reduce the difficulty with the solution to SDVRP, based on analyzing properties of the optimal solution, the original model is transformed to the e-quivalent modified SDVRP through enforcing constraints of the original model. In the process of solving the modified SDVRP model with ant colony algorithm, exploring new routes and 2-opt are combined to avoid premature convergence. The experiments demonstrate that the computing results are stable: The bias between the worst solution and the best solution is only 1.80%.

  7. Self-Assembled Cationic Biodegradable Nanoparticles from pH-Responsive Amino-Acid-Based Poly(Ester Urea Urethane)s and Their Application As a Drug Delivery Vehicle. (United States)

    He, Mingyu; Potuck, Alicia; Kohn, Julie C; Fung, Katharina; Reinhart-King, Cynthia A; Chu, Chih-Chang


    The objective of this study is to develop a new family of biodegradable and biologically active copolymers and their subsequent self-assembled cationic nanoparticles as better delivery vehicles for anticancer drugs to achieve the synergism between the cytotoxicity effects of the loaded drugs and the macrophage inflammatory response of the delivery vehicle. This family of cationic nanoparticles was formulated from a new family of amphiphilic cationic Arginine-Leucine (Arg-Leu)-based poly(ester urea urethane) (Arg-Leu PEUU) synthesized from four building blocks (amino acids, diols, glycerol α-monoallyl ether, and 1,6 hexamethylene diisocyanate). The chemical, physical, and biological properties of Arg-Leu PEUU biomaterials can be tuned by controlling the feed ratio of the four building blocks. The Arg-Leu PEUU copolymers have weight-average molecular weights from 13.4 to 16.8 kDa and glass-transition temperatures from -3.4 to -4.6 °C. The self-assembled cationic nanoparticles (Arg-Leu PEUU NPs) were prepared using a facile dialysis method. Arg-Leu PEUU NPs have average diameters ranging from 187 to 272 nm, show good biocompatibility with 3T3 fibroblasts, and they support bovine aortic endothelial cell (BAEC) proliferation and adhesion. Arg-Leu PEUU NPs also enhanced the macrophages' production of tumor necrosis factor-α (TNF-α) and nitric oxide (NO), but produced relatively low levels of interleukin-10 (IL-10), and therefore, the antitumor activity of macrophages might be enhanced. Arg-Leu PEUU NPs were taken up by HeLa cells after 4 h of incubation. The in vitro hemolysis assay showed the cationic Arg-Leu PEUU NPs increased their chance of endosomal escape at a more acidic pH. Doxorubicin (DOX) was successfully incorporated into the Arg-Leu PEUU NPs, and the DOX-loaded Arg-Leu PEUU NPs exhibited a pH-dependent drug release profile with accelerated release kinetics in a mild acidic condition. The DOX-loaded 6-Arg-4-Leu-4 A/L-2/1 NPs showed higher HeLa cell

  8. pH-Sensitive Delivery Vehicle Based on Folic Acid-Conjugated Polydopamine-Modified Mesoporous Silica Nanoparticles for Targeted Cancer Therapy. (United States)

    Cheng, Wei; Nie, Junpeng; Xu, Lv; Liang, Chaoyu; Peng, Yunmei; Liu, Gan; Wang, Teng; Mei, Lin; Huang, Laiqiang; Zeng, Xiaowei


    In this study, we introduced a targeting polymer poly(ethylene glycol)-folic acid (PEG-FA) on the surface of polydopamine (PDA)-modified mesoporous silica nanoparticles (MSNs) to develop the novel nanoparticles (NPs) MSNs@PDA-PEG-FA, which were employed as a drug delivery system loaded with doxorubicin (DOX) as a model drug for cervical cancer therapy. The chemical structure and properties of these NPs were characterized by transmission electron microscopy, X-ray photoelectron spectroscopy, N2 adsorption/desorption, dynamic light scattering-autosizer, thermogravimetric analysis, and Fourier transform infrared spectroscopy. The pH-sensitive PDA coating served as a gatekeeper. The in vitro drug release experiments showed pH-dependent and sustained drug release profiles that could enhance the therapeutic anticancer effect and minimize potential damage to normal cells due to the acidic microenvironment of the tumor. These MSNs@PDA-PEG-FA achieved significantly high targeting efficiency, which was demonstrated by the in vitro cellular uptake and cellular targeting assay. Compared with that of free DOX and DOX-loaded NPs without the folic targeting ligand, the FA-targeted NPs exhibited higher antitumor efficacy in vivo, implying that they are a highly promising potential carrier for cancer treatments.

  9. Lecithin-gold hybrid nanocarriers as efficient and pH selective vehicles for oral delivery of diacerein-In-vitro and in-vivo study. (United States)

    Javed, Ibrahim; Hussain, Syed Zajif; Shahzad, Atif; Khan, Jahanzeb Muhammad; Ur-Rehman, Habib; Rehman, Mubashar; Usman, Faisal; Razi, Muhammad Tahir; Shah, Muhammad Raza; Hussain, Irshad


    We report the synthesis and evaluation of lecithin-gold hybrid nanocarriers for the oral delivery of drugs with improved pharmacokinetics, Au-drug interactive bioactivity and controlled drug releasing behavior at physiological pH inside human body. For this purpose, diacerein, a hydrophobic anti-arthritic drug, was loaded in lecithin NPs (LD NPs), which were further coated by Au NPs either by in-situ production of Au NPs on LD NPs or by employing pre-synthesized Au NPs. All LDAu NPs were found to release drug selectively at the physiological pH of 7.4 and showed 2.5 times increase in the oral bioavailability of diacerein. Pharmacological efficacy was significantly improved i.e., greater than the additive effect of diacerein and Au NPs alone. LDAu NPs started suppressing inflammation at first phase, whereas LD NPs showed activity in the second phase of inflammation. These results indicate the interaction of Au NPs with prostaglandins and histaminic mediators of first phase of carrageenan induced inflammation. Acute toxicity study showed no hepatic damage but the renal toxicity parameters were close to the upper safety limits. Toxicity parameters were dependent on surface engineering of LDAu NPs. Apart from enhancing the oral bioavailability of hydrophobic drugs and improving their anti-inflammatory activity, these hybrid nanocarriers may have potential applications in gold-based photothermal therapy and the tracing of inflammation at atherosclerotic and arthritic site.

  10. 混流制造车间物料配送路径优化%Optimization of material delivery vehicle routing plan-ning problem in flow manufacturing system

    Institute of Scientific and Technical Information of China (English)

    高贵兵; 张红波; 张道兵; 岳文辉


    Timely and accurately delivering the material to the workstations in the flow-manufacturing system is not only the guarantee of the normal running, but also the fundamental of the efficient operation of the system. For the Material Delivery Vehicle Routing optimization Problem(MDVRP)in the flow manufacturing, the optimization goals, the constraints and the influencing factors are considered, and the multi-objective optimization model is built by considering the shortest travel distance of vehicles, maximizing the utilization of vehicles and minimizing the number of distributions. According to the specific circumstances of the problem, a Double Progressive Evolutionary Multi-Objective Optimization Algorithm (DPEMOA)is designed to solve the multi-objective optimization problem. The two-tier progressive evolutionary process is proposed. The improved genetic operator is implemented, and the specific implementation process is manifested. The validity of the model and algorithm are verified by a case of flow manufacturing system.%物料及时、准确送到混流制造系统的各工位节点不仅是系统正常运行的保证,也是混流系统高效运转的根本。针对混流制造系统物料配送车辆路径优化问题,从优化目标、约束条件和影响因素等方面考虑,建立了以车辆行驶距离最短、车辆利用率最大和配送次数最少为优化目标的多目标配送车辆路径优化模型。根据问题的具体情况,设计了解决该多目标优化问题的双层递进进化多目标优化算法,给出了算法的进化过程和交叉、变异模式及其实现过程。通过一个混流装配系统的实例证明了所建立的模型和设计算法的有效性。

  11. Porous microspheres as promising vehicles for the topical delivery of poorly soluble asiaticoside accelerate wound healing and inhibit scar formation in vitro &in vivo. (United States)

    Zhang, Chen-Zhen; Niu, Jie; Chong, Yee-Song; Huang, Yan-Fen; Chu, Yang; Xie, Sheng-Yang; Jiang, Zhi-Hong; Peng, Li-Hua


    Asiaticoside is a natural compound possessing diverse pharmacological effects with great potential for clinical use. However, the low solubility and oil-water partition coefficient of asiaticoside lead to reduced effect and limited application. This study aims to construct a porous microsphere for the sustained release of asiaticoside to improve its absorption and enhance the therapeutic effects. Parameters of the formulations, including the drug to polymer ratio, solvent amounts of the inner and external phases, the stirring speed for preparation, and the drug entrapment efficiency were investigated and optimized. Particle size, morphology, pores structure, and Fourier transform infrared spectrum of the microsphere were characterized. The release kinetics and cellular uptake profiles of the asiaticoside-microspheres were examined. The therapeutic effects of asiaticoside-microspheres on wound healing and skin appendages regeneration were investigated in vitro & in vivo. Results showed that the optimized asiaticoside-microspheres possess spherical spongy structure with cylindrical holes. Asiaticoside can be loaded in the microsphere with high efficiency and released with sustained manner. The cellular uptake of asiaticoside from the microspheres was increased with 9.1 folds higher than that of free solution. Asiaticoside-microspheres expressed the strong promotion in the proliferation, migration of keratinocytes and wound scratching healing in vitro. More importantly, they significantly accelerated the re-epithelization, collagen synthesis and pro-angiogenesis in the rat full-skin wound healing. Porous microsphere was shown a novel carrier for the sustained delivery of poorly soluble asiaticoside, with absorption and therapeutic effects improved. Asiaticoside-microsphere is a promising topical preparation with excellent regenerative effects for the wound therapy.

  12. Analogy between dynamics of thermo-rheological and piezo-rheological pendulums

    Energy Technology Data Exchange (ETDEWEB)

    Hedrih, K [Faculty of Mechanical Engineering University of Nis, Mathematical Institute SANU, ul. Vojvode Tankosic 3/V/22, 18000-Nis (Serbia)], E-mail:, E-mail: khedrih@eunet.yu


    The constitutive stress-strain relations of the standard thermo-rheological and piezo-rheological hereditary element in differential form as well as in two different integro-differential forms are defined. The considered problem of a thermo-rheological hereditary discrete system nonlinear dynamics in the form of thermo-rheological double pendulum system with coupled pendulums gets the significance of two constrained bodies in plane motion problem, as a problem important for studying a sensor dynamics or actuator dynamics in active structure dynamics. System of the averaged equations in the first approximation for amplitudes and phases are derived and qualitatively analyzed. Analogy between nonlinear dynamics of the double pendulum systems with thermo-rheological and piezo-rheological properties between pendulums is pointed out.

  13. Rheology v.2 theory and applications

    CERN Document Server

    Eirich, Frederick


    Rheology: Theory and Applications, Volume II deals with the specific rheological subjects, such as deformational behavior in relation to the classic subjects and topics of rheology. This volume is divided into 13 chapters. Considerable chapters are devoted to the theory and aspects of viscoelastic and relaxation phenomena, as well as the applied theory concerning substances related to these phenomena, including elastomers, gelatins, and fibers. Other chapters cover the general principles of geological deformations derived from the study of less """"immobile"""" objects. The remaining chapt

  14. Experimental investigation on the rheology of foams

    Energy Technology Data Exchange (ETDEWEB)

    Bonilla, L. F. [Univ. Surcolombiana, Neiva, Huila (Colombia); Shah, S. N. [Oklahoma Univ., Norman, OK (United States)


    The rheology of foams was investigated using aqueous and gelled foams and employing a pipe-type viscometer. Surfactant at 0.5 per cent concentration was used as the foaming agent. Results indicated that foam fluid rheology can be adequately characterized by the Herschel-Bulkley model. The experimental data served as the starting point for the development of new empirical correlations to predict foam fluid apparent viscosity. The use of these new correlations is expected to provide more accurate estimates of foam fluid rheological properties. 14 refs., 5 tabs., 14 figs.

  15. Rheology of dispersions principles and applications

    CERN Document Server

    Tadros, Tharwat F


    A dispersion is a system of unmixable phases in which one phase is continuous and at least one is finely distributed. Examples are found in many industrial applications, including emulsions, suspensions, foams, and geld. The control of their flow characteristics - rheology - is essential in their preparation, long-term physical stability and application. Filling the need for a practical, up-to-date book connecting the stability/instability of the dispersion to its rheological behavior, this title aids in understanding the principles of rheology and the techniques that can be applied. From the

  16. Theory of rheology in confinement. (United States)

    Aerov, Artem A; Krüger, Matthias


    The viscosity of fluids is generally understood in terms of kinetic mechanisms, i.e., particle collisions, or thermodynamic ones as imposed through structural distortions upon, e.g., applying shear. Often the latter are more relevant, which allows a simpler theoretical description, and, e.g., (damped) Brownian particles can be considered good fluid model systems. We formulate a general theoretical approach for rheology in confinement, based on microscopic equations of motion and classical density functional theory. Specifically, we discuss the viscosity for the case of two parallel walls in relative motion as a function of the wall-to-wall distance, analyzing its relation to the slip length found for a single wall. The previously observed [A. A. Aerov and M. Krüger, J. Chem. Phys. 140, 094701 (2014).] deficiency of inhomogeneous (unphysical) stresses under naive application of shear in confinement is healed when hydrodynamic interactions are included.

  17. The Rheology of Concentrated Suspensions

    Energy Technology Data Exchange (ETDEWEB)

    Andreas Acrivos


    Research program on the rheological properties of flowing suspensions. The primary purpose of the research supported by this grant was to study the flow characteristics of concentrated suspensions of non-colloidal solid particles and thereby construct a comprehensive and robust theoretical framework for modeling such systems quantitatively. At first glance, this seemed like a modest goal, not difficult to achieve, given that such suspensions were viewed simply as Newtonian fluids with an effective viscosity equal to the product of the viscosity of the suspending fluid times a function of the particle volume fraction. But thanks to the research findings of the Principal Investigator and of his Associates, made possible by the steady and continuous support which the PI received from the DOE Office of Basic Energy Sciences, the subject is now seen to be more complicated and therefore much more interesting in that concentrated suspensions have been shown to exhibit fascinating and unique rheological properties of their own that have no counterpart in flowing Newtonian or even non-Newtonian (polymeric) fluids. In fact, it is generally acknowledged that, as the result of these investigations for which the PI received the 2001 National Medal of Science, our understanding of how suspensions behave under flow is far more detailed and comprehensive than was the case even as recently as a decade ago. Thus, given that the flow of suspensions plays a crucial role in many diverse physical processes, our work has had a major and lasting impact in a subject having both fundamental as well as practical importance.

  18. 求解异车型同时集送问题的多属性标签算法%A heuristic algorithm for vehicle routing problem with heterogeneous fleet, simultaneous pickup and delivery

    Institute of Scientific and Technical Information of China (English)

    田宇; 伍炜勤


    针对实际运输中顾客对不同车型、同时集送货物的多样化需求,文章建立了异车型同时集送车辆路径模型(vehicle routing problem with heterogeneous fleet,simultaneous pickup and delivery,VRPHSPD),并构建了基于多属性标签的蚁群系统算法(multi-label based ant colony system,MLACS)进行求解.该算法利用面向对象理念,分别对客户、车辆及其行驶路径构建多属性标签,首先用近邻法生成初始路径,再通过蚁群算法的搜索规则对客户和车辆标签进行匹配,从而得优化的结果.通过公开算例、实际应用案例的验证表明,MLACS算法能成功求解VRPHSPD问题,具有较高的求解质量、运算效率以及实际应用意义.

  19. 带有次序限制的装卸一体化车辆路径问题研究%The Study for Vehicle Routing Problem with Simultaneous Delivery and Pickup and Order limit

    Institute of Scientific and Technical Information of China (English)

    黄秋爱; 李珍萍


    The vehicle routing problem with simultaneous delivery and pickup is studied in this paper. According to the practical case, the constraint of order limit is added. Then the mathematical model aiming at finding out the minimum distance is established. At the same time, an improved genetic algorithm based on the best selection method is designed and used to solve this model. Finally, the validity of the model and algorithm are tested by practical example.%研究了装卸一体化的车辆路径问题,根据问题的实际情况,增加了带有次序限制条件,并以总行驶路线最短为目标,建立了数学模型,并根据模型的特点,用改进的遗传算法进行求解。最后,通过具体实例验证了模型及算法的有效性。

  20. PLGA-PEG-PLGA microspheres as a delivery vehicle for antisense oligonucleotides to CTGF: Implications on post-surgical peritoneal adhesion prevention (United States)

    Azeke, John Imuetinyan-Jesu, Jr.

    Abdominal adhesions are the aberrant result of peritoneal wound healing commonly associated with surgery and inflammation. A subject of a large number of studies since the first half of the last century, peritoneal adhesion prevention has, for the most part, evaded the scientific community and continues to cost Americans an estimated $2-4 billion annually. It is known that transforming growth factor-beta (TGF-beta) plays a key role in the wound healing cascade; however, suppression of this multifunctional growth factor's activity may have more harmful consequences than can be tolerated. As a result, much attention has fallen on connective tissue growth factor (CTGF), a downstream mediator of TGF-beta's fibrotic action. It has been demonstrated in several in vitro models, that the suppression of CTGF hinders fibroblast proliferation, a necessary condition for fibrosis. Furthermore, antisense oligonucleotides (antisense oligos, AO) to CTGF have been shown to knock down CTGF mRNA levels by specifically hindering the translation of CTGF protein. Antisense technologies have met with a great deal of excitement as a viable means of preventing diseases such as adhesions by hindering protein translation at the mRNA level. However, the great challenge associated with the use of these drugs lies in the short circulation time when administered "naked". Viral delivery systems, although excellent platforms in metabolic studies, are not ideal for diagnostic use because of the inherent danger associated with viral vectors. Microparticles made of biodegradable polymers have therefore presented themselves as a viable means of delivering these drugs to target cells over extended periods. Herein, we present two in vivo studies confirming the up-regulation of TGF-beta protein and CTGF mRNA following injury to the uterine tissues of female rats. We were able to selectively knockdown post-operative CTGF protein levels following surgery, however, our observations led us to conclude that

  1. Novel materials as vehicles for target drug delivery system%纳米靶向给药系统载体材料的研究进展

    Institute of Scientific and Technical Information of China (English)

    曹文疆; 程江; 王昶光


    目的:综述及讨论近年来新材料在靶向给药系统载体材料方面的应用及存在问题.资料来源:以网络数据库资源为主,查询ScienceDirect,Pubmed,Springer,Ovid等数据库1995-01/2006-06关于靶向给药系统载体材料方面的相关文献,检索词"Target drug delivery system"and"Materials",限定文章的语种种类为"English";同时检索CNKI数据库2001-01/2006-06的相关文章为补充,限定文章语种种类为中文,检索关键词"靶向给药系统,载体材料".资料选择:对资料进行初审,纳入标准:①关于靶向给药系统的研究.②应用的较新的材料作为药物载体.排除标准:重复性研究.资料提炼:共收集到122篇文献,98篇符合纳入标准,取其中有关新型载体材料应用于靶向给药系统的30篇相关文献进行归纳总结.资料综合:靶向给药是目前药剂学领域的研究热点之一,但多年来转化为产品的研究成果极为少见.其中关键问题之一就是药物载体材料的研究瓶颈,药剂学研究与材料学研究间学科交叉与衔接的严重滞后阻碍了新型给药系统的产业化.结论:新型给药系统载体材料研究开发尤为重要,载体材料应用的安全性一旦解决,必将带来新型给药系统全面用于临床的新局面,从而使药效得到更好的发挥,提高疾病的预防治疗能力.

  2. Correlation of chitosan's rheological properties to its ability to electrospin (United States)

    Krause, Wendy E.; Queen, Hailey A.; Klossner, Rebecca R.; Coughlin, Andrew J.


    Chitosan, derived from chitin found in the exoskeleton of crustaceans, has been investigated extensively for use in biomedical applications ranging from drug delivery to scaffolds for tissue engineering. Therefore, forming nanofibers of this linear polysaccharide is desirable for use in such applications, because the nanofibers can be tailored to mimic the size and porosity of the extracellular matrix. Electrostatic spinning (electrospinning) is a convenient method to produce nonwoven mats of nanofibers. The ability of the solutions to successfully electospin is closely correlated with the rheological properties of the solutions. Chitosan is challenging to electrospin due to its relatively high viscosity at modest concentrations. Solutions of chitosan blended with poly(ethylene oxide) (PEO) have been electrospun successfully with freshly prepared solutions. If the blended solutions are stored, they do not readily electrospin. Moreover, chitosan/PEO blend solutions show a drastic decrease in zero shear rate viscosity over time, which can be attributed to phase separation. The challenges associated with electrospinning charged biopolymers (chitosan is cationic) will be discussed in terms of their rheological properties. Successes and failures will be highlighted and compared results for readily electrospun neutral polymers.

  3. On shear rheology of gel propellants

    Energy Technology Data Exchange (ETDEWEB)

    Rahimi, Shai; Peretz, Arie [RAFAEL, MANOR Propulsion and Explosive Systems Division, Haifa (Israel); Natan, Benveniste [Faculty of Aerospace Engineering, Technion - Israel Institute of Technology, Haifa (Israel)


    Selected fuel, oxidizer and simulant gels were prepared and rheologically characterized using a rotational rheometer. For fuel gelation both organic and inorganic gellants were utilized, whereas oxidizers and simulants were gelled with addition of silica and polysaccharides, respectively. The generalized Herschel-Bulkley constitutive model was found to most adequately represent the gels studied. Hydrazine-based fuels, gelled with polysaccharides, were characterized as shear-thinning pseudoplastic fluids with low shear yield stress, whereas inhibited red-fuming nitric acid (IRFNA) and hydrogen peroxide oxidizers, gelled with silica, were characterized as yield thixotropic fluids with significant shear yield stress. Creep tests were conducted on two rheological types of gels with different gellant content and the results were fitted by Burgers-Kelvin viscoelastic constitutive model. The effect of temperature on the rheological properties of gel propellant simulants was also investigated. A general rheological classification of gel propellants and simulants is proposed. (Abstract Copyright [2007], Wiley Periodicals, Inc.)

  4. Using Greener Gels To Explore Rheology


    Matharu, Avtar Singh; Hurst, Glenn; Garrett, Brendan


    A laboratory experiment was developed to investigate the rheological properties of a green calcium-cross-linked alginate gel as an alternative to the traditional borax-cross-linked poly(vinyl alcohol) gel. As borax is suspected of damaging fertility and the unborn child, a safe, green alternative is necessary. The rheological properties of a sodium alginate solution were examined as a function of temperature using capillary viscometry. Gelation and degelation processes were followed using rot...

  5. On the cytoskeleton and soft glassy rheology. (United States)

    Mandadapu, Kranthi K; Govindjee, Sanjay; Mofrad, Mohammad R K


    The cytoskeleton is a complex structure within the cellular corpus that is responsible for the main structural properties and motilities of cells. A wide range of models have been utilized to understand cytoskeletal rheology and mechanics (see e.g. [Mofrad, M., Kamm, R., 2006. Cytoskeletal Mechanics: Models and Measurements. Cambridge University Press, Cambridge]). From this large collection of proposed models, the soft glassy rheological model (originally developed for inert soft glassy materials) has gained a certain traction in the literature due to the close resemblance of its predictions to certain mechanical data measured on cell cultures [Fabry, B., Maksym, G., Butler, J., Glogauer, M., Navajas, D., Fredberg, J., 2001. Scaling the microrheology of living cells. Physical Review Letters 87, 14102]. We first review classical linear rheological theory in a concise fashion followed by an examination of the soft glassy rheological theory. With this background we discuss the observed behavior of the cytoskeleton and the inherent limitations of classical rheological models for the cytoskeleton. This then leads into a discussion of the advantages and disadvantages presented to us by the soft glassy rheological model. We close with some comments of caution and recommendations on future avenues of exploration.

  6. Rheological characteristics of synthetic road binders

    Energy Technology Data Exchange (ETDEWEB)

    Gordon D. Airey; Musarrat H. Mohammed; Caroline Fichter [University of Nottingham, Nottingham (United Kingdom)


    This paper deals with the synthesis of polymer binders from monomers that could in future be derived from renewable resources. These binders consist of polyethyl acrylate (PEA) of different molecular weight, polymethyl acrylate (PMA) and polybutyl acrylate (PBA), which were synthesised from ethyl acrylate, methyl acrylate and butyl acrylate, respectively, by atom transfer radical polymerization (ATRP). The fundamental rheological properties of these binders were determined by means of a dynamic shear rheometer (DSR) using a combination of temperature and frequency sweeps. The results indicate that PEA has rheological properties similar to that of 100/150 penetration grade bitumen, PMA similar rheological properties to that of 10/20 penetration grade bitumen, while PBA, due to its highly viscous nature and low complex modulus, cannot be used on its own as an asphalt binder. The synthetic binders were also combined with conventional penetration grade bitumen to produce a range of bitumen-synthetic polymer binder blends. These blends were batched by mass in the ratio of 1:1 or 3:1 and subjected to the same DSR rheological testing as the synthetic binders. The blends consisting of a softer bitumen (70/100 pen or 100/150 pen) with a hard synthetic binder (PMA) tended to be more compatible and therefore stable and produced rheological properties that combined the properties of the two components. The synthetic binders and particularly the extended bitumen samples (blends) produced rheological properties that showed similar characteristics to elastomeric SBS PMBs. 30 refs., 12 figs., 2 tabs.

  7. Rheology of welding: Field constraints (United States)

    Russell, K.; Quane, S.


    Pyroclastic deposits emplaced at high temperature and having sufficient thickness become welded via sintering, compaction and flattening of hot glassy particles. The welding process is attended by pronounced changes in the physical properties of the deposit and welding intensity can be tracked by measuring the density, porosity, fabric or strength of samples. Ultimately, the intensity of welding reflects the aggregate effects of load and residence time at temperatures above the glass transition temperature (Tg). This results in welding intensity varying with stratigraphic depth; vertical sections through welded ignimbrite deposits commonly show maximum (e.g., density) or minimum (porosity) values in physical properties in the lower half (30--40% above the base) of the unit. Here we explore the extent to which these data, serving as proxies for strain, can be used constrain the rheological properties of the pyroclastic deposit during the welding process. Our data include measurements of density, porosity, fabric and rock strength as a function of stratigraphic position for 4 sections through the Bandelier tuff, New Mexico. These profiles record changes in physical properties and, thus, map the cumulative strain associated with welding as a function of depth (load). We have used simple conductive heat transfer models to estimate cooling curves for each sample. Essentially, these curves provide the residence time within the "welding window" for each sample. The curves are dependent on sample position, thickness of ignimbrite, emplacement temperature and the glass transition temperature of the material. The unknowns in the problem are a number of physical constants in a generalized power-law relationship between strain-rate (ɛ') and stress (σ) for steady-state creep at constant load: ɛ' = A σ^n e[-Q/R T]. Specifically, we adopt an inverse-model approach whereby the observations on the natural material are used to constrain the pre-exponential constant (A), stress

  8. The Vehicle Routing Problem with Limited Vehicle Capacities

    Directory of Open Access Journals (Sweden)

    Fernando Taracena Sanz


    Full Text Available The vehicle routing problem (VRP has been an important research topic during the last decades because of his vital role in the productive systems efficiency. Most of the work done in this area has been directed to solve large scale problems which may not apply for small companies which are a very important engine of the world economy. This paper approaches the problem when limited vehicle resources are present and road transportation is used. This study assumes variable customer orders. Variable volume and weight vehicle capacities are considered and the proposed algorithm develops the vehicle delivery routes and the set of customer orders to deliver per vehicle minimizing a cost objective function. In sampling small company’s logistics costs, big cost savings are found when using the proposed method.

  9. The rheology of icy satellites (United States)

    Sammis, C. G.


    High-temperature creep in orthoenstatite under conditions of controlled oxygen fugacity was studied. It was found that creep was conttrolled by the extremely thin layer of SiO2 which wetted the grain boundaries. Slight reduction of the (Mg, Fe)SiO3 enstatite during hot pressing produced microscopic particles of Fe and the thin film of intergranular SiO2. This result highlights another complication in determining the flow properties of iron bearing silicates which constitute the bulk of terrestrial planets and moons. The Phenomenon may be important in the ductile formation of any extraterrestrial body which is formed in a reducing environment. The rheology of dirty ice was studied. This involves micromechanical modeling of hardening phenomena due to contamination by a cosmic distribution of silicate particles. The larger particles are modeled by suspension theory. In order to handle the distribution of particles sizes, the hardening is readed as a critical phenomenon, and real space renormalization group techniques are used. Smaller particles interact directly with the dislocations. The particulate hardening effect was studied in metals. The magnitude of such hardening in ice and the defect chemistry of ice are studied to assess the effects of chemical contamination by methane, ammonia, or other likely contaminants.

  10. Electric vehicles (United States)


    Quiet, clean, and efficient, electric vehicles (EVs) may someday become a practical mode of transportation for the general public. Electric vehicles can provide many advantages for the nation's environment and energy supply because they run on electricity, which can be produced from many sources of energy such as coal, natural gas, uranium, and hydropower. These vehicles offer fuel versatility to the transportation sector, which depends almost solely on oil for its energy needs. Electric vehicles are any mode of transportation operated by a motor that receives electricity from a battery or fuel cell. EVs come in all shapes and sizes and may be used for different tasks. Some EVs are small and simple, such as golf carts and electric wheel chairs. Others are larger and more complex, such as automobile and vans. Some EVs, such as fork lifts, are used in industries. In this fact sheet, we will discuss mostly automobiles and vans. There are also variations on electric vehicles, such as hybrid vehicles and solar-powered vehicles. Hybrid vehicles use electricity as their primary source of energy, however, they also use a backup source of energy, such as gasoline, methanol or ethanol. Solar-powered vehicles are electric vehicles that use photovoltaic cells (cells that convert solar energy to electricity) rather than utility-supplied electricity to recharge the batteries. These concepts are discussed.

  11. A rheological and microstructural characterisation of bigels for cosmetic and pharmaceutical uses. (United States)

    Lupi, Francesca R; Shakeel, Ahmad; Greco, Valeria; Oliviero Rossi, Cesare; Baldino, Noemi; Gabriele, Domenico


    Bigels are biphasic systems formed by water-based hydrogels and oil-based organogels, mainly studied, in the last few years, for pharmaceutical and cosmetic application focused on the controlled delivery of both lipophilic and hydrophilic active agents. The rheological properties of bigels depend on both the amount and the rheological characteristics of single structured phases. Moreover, it can be expected that, at large fractions of one of the starting gels, systems more complex than oil-in-water or water-in-oil can be obtained, yielding bicontinuous or matrix-in-matrix arrangement. Model bigels were investigated from a microstructural (i.e. microscopy and electrical conductivity tests) and rheological point of view. The hydrogel was prepared by using a low-methoxyl pectin whereas the organogel was prepared by using olive oil and, as gelator, a mixture of glyceryl stearate and policosanol. Model bigels were obtained by increasing the amount of organogel mixed with the hydrogel, and microstructural characterisation evidenced an organogel-in-hydrogel behaviour for all investigated samples, even though at the highest organogel content a more complex structure seems to arise. A semi-empirical model, based on theoretical equations developed for suspensions of elastic spheres in elastic media, was proposed to relate bigel rheological properties to single phase properties and fractions.

  12. Linear correlation between rheological, mechanical and mucoadhesive properties of polycarbophil polymer blends for biomedical applications. (United States)

    De Souza Ferreira, Sabrina Barbosa; Da Silva, Jéssica Bassi; Borghi-Pangoni, Fernanda Belincanta; Junqueira, Mariana Volpato; Bruschi, Marcos Luciano


    Polycarbophil is widely used in a variety of pharmaceutical formulations, mainly for their strong ability to adhere to the epithelial and mucous barriers (bio/mucoadhesion). On the other hand, its association with the thermoresponsive polymer (poloxamer 407) has been poorly explored. This work investigates the rheological, mechanical and mucoadhesive properties of polymer blends containing polycarbophil and poloxamer 407, in order to select the best formulations for biomedical and pharmaceutical applications. Mechanical (hardness, compressibility, adhesiveness, softness, and mucoadhesion) and rheological characteristics (consistency index, yield value and hysteresis area) showed that 20% (w/w) poloxamer 407- polymer blends exhibited higher values parameters. However, the rheological interaction parameter, which was more sensible than the mechanical interaction parameter, revealed higher synergism for systems comprising 15% (w/w) poloxamer 407, due to the system organization and polymers' properties. Furthermore, gelation temperatures were appropriated, suggesting that polymer blends can be used as biomedical materials, and displaying easy administration, enhanced retention and prolonged residence time at the site of application. Therefore, rheological, mechanical and mucoadhesive characterization provided a rational basis for selecting appropriated systems, useful for mucoadhesive drug delivery systems and biomedical applications.

  13. 短途配送中车辆配装货物的隔票问题探讨%Discussion on the Separation Problem of Loading Goods in Short Distance Delivery by Vehicles

    Institute of Scientific and Technical Information of China (English)



    For a long time,in order to improve the distribution efficiency,the logistical industry is very concerned about the distribution route optimization.But the reality is,the real travel time which can be compressed is very limited,and the proportion in the process of the total distribution is not high.As a matter of fact,sort-out,unloading and handover sector,especially the mixed-up stowage phenomenon for improper separation are the true causes which influence the efficiency of the distribution.This paper makes analysis on the distribution process of mixed-up stowage and improper separation,with the help of separate-lots technology and operating procedures on marine shipping,discusses on separate-lots technology and principles of loading goods in short distance delivery by vehicles,puts forward the corresponding solutions.%长期以来,物流行业非常关注配送线路优化,借以提升配送效率。但是现实情况是真正的行驶时间可压缩空间很小,而且在总的配送过程中比例不大。真正影响配送效率的是理货卸车交接环节,特别是因隔票不清导致的混票现象。文中对配送过程的混票和隔票不清的过程进行分析,借助海运中隔票技术和操作规程,对短途配送中车辆配装的隔票技术和原则进行讨论,提出对应的解决对策。

  14. Bioresponsive matrices in drug delivery

    Directory of Open Access Journals (Sweden)

    Ye George JC


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

  15. Initial rheological description of high performance concretes

    Directory of Open Access Journals (Sweden)

    Alessandra Lorenzetti de Castro


    Full Text Available Concrete is defined as a composite material and, in rheological terms, it can be understood as a concentrated suspension of solid particles (aggregates in a viscous liquid (cement paste. On a macroscopic scale, concrete flows as a liquid. It is known that the rheological behavior of the concrete is close to that of a Bingham fluid and two rheological parameters regarding its description are needed: yield stress and plastic viscosity. The aim of this paper is to present the initial rheological description of high performance concretes using the modified slump test. According to the results, an increase of yield stress was observed over time, while a slight variation in plastic viscosity was noticed. The incorporation of silica fume showed changes in the rheological properties of fresh concrete. The behavior of these materials also varied with the mixing procedure employed in their production. The addition of superplasticizer meant that there was a large reduction in the mixture's yield stress, while plastic viscosity remained practically constant.

  16. Fault rheology beyond frictional melting. (United States)

    Lavallée, Yan; Hirose, Takehiro; Kendrick, Jackie E; Hess, Kai-Uwe; Dingwell, Donald B


    During earthquakes, comminution and frictional heating both contribute to the dissipation of stored energy. With sufficient dissipative heating, melting processes can ensue, yielding the production of frictional melts or "pseudotachylytes." It is commonly assumed that the Newtonian viscosities of such melts control subsequent fault slip resistance. Rock melts, however, are viscoelastic bodies, and, at high strain rates, they exhibit evidence of a glass transition. Here, we present the results of high-velocity friction experiments on a well-characterized melt that demonstrate how slip in melt-bearing faults can be governed by brittle fragmentation phenomena encountered at the glass transition. Slip analysis using models that incorporate viscoelastic responses indicates that even in the presence of melt, slip persists in the solid state until sufficient heat is generated to reduce the viscosity and allow remobilization in the liquid state. Where a rock is present next to the melt, we note that wear of the crystalline wall rock by liquid fragmentation and agglutination also contributes to the brittle component of these experimentally generated pseudotachylytes. We conclude that in the case of pseudotachylyte generation during an earthquake, slip even beyond the onset of frictional melting is not controlled merely by viscosity but rather by an interplay of viscoelastic forces around the glass transition, which involves a response in the brittle/solid regime of these rock melts. We warn of the inadequacy of simple Newtonian viscous analyses and call for the application of more realistic rheological interpretation of pseudotachylyte-bearing fault systems in the evaluation and prediction of their slip dynamics.

  17. Understanding rheological hysteresis in soft glassy materials. (United States)

    Radhakrishnan, Rangarajan; Divoux, Thibaut; Manneville, Sébastien; Fielding, Suzanne M


    Motivated by recent experimental studies of rheological hysteresis in soft glassy materials, we study numerically strain rate sweeps in simple yield stress fluids and viscosity bifurcating yield stress fluids. Our simulations of downward followed by upward strain rate sweeps, performed within fluidity models and the soft glassy rheology model, successfully capture the experimentally observed monotonic decrease of the area of the rheological hysteresis loop with sweep time in simple yield stress fluids, and the bell shaped dependence of hysteresis loop area on sweep time in viscosity bifurcating fluids. We provide arguments explaining these two different functional forms in terms of differing tendencies of simple and viscosity bifurcating fluids to form shear bands during the sweeps, and show that the banding behaviour captured by our simulations indeed agrees with that reported experimentally. We also discuss the difference in hysteresis behaviour between inelastic and viscoelastic fluids. Our simulations qualitatively agree with the experimental data discussed here for four different soft glassy materials.


    Institute of Scientific and Technical Information of China (English)

    C.J. Sun; H.R. Geng; Y.S. Shen; X.Y. Teng; Z.X. Yang


    The rheology feature of Sb, Bi melt and alloys was studied using coaxial cylinder high-temperature viscometer. The results showed that the curve of torsion-rotational speed for Sb melt presents a linear relation in all measured temperature ranges, whereas for the Bi melt, the curve presents obvious non-Newtonian feature within the low temperature range and at relative high shear stress. The rheology feature of Sb80Bi20 and Sb20Bi80, alloy melts was well correlated with that of Sb and Bi, respectively. It is considered that the rheology behavior of Sb melt plays a crucial role in Sb80Bi20, alloy and that of Bi melt plays a crucial role in Sb20Bi80 alloy.

  19. The debris-flow rheology myth (United States)

    Iverson, R.M.; ,


    Models that employ a fixed rheology cannot yield accurate interpretations or predictions of debris-flow motion, because the evolving behavior of debris flows is too complex to be represented by any rheological equation that uniquely relates stress and strain rate. Field observations and experimental data indicate that debris behavior can vary from nearly rigid to highly fluid as a consequence of temporal and spatial variations in pore-fluid pressure and mixture agitation. Moreover, behavior can vary if debris composition changes as a result of grain-size segregation and gain or loss of solid and fluid constituents in transit. An alternative to fixed-rheology models is provided by a Coulomb mixture theory model, which can represent variable interactions of solid and fluid constituents in heterogeneous debris-flow surges with high-friction, coarse-grained heads and low-friction, liquefied tails. ?? 2003 Millpress.

  20. Introduction to Rheology and Application to Geophysics (United States)

    Ancey, C.

    This chapter gives an overview of the major current issues in rheology through a series of different problems of particular relevance to geophysics. For each topic considered here, we will outline the key elements and point the reader to ward the most helpful references and authoritative works. The reader is also referred to available books introducing rheology [1, 2] for a more complete presentation and to the tutorial written by Middleton and Wilcock on mechanical and rheological app lications in geophysics [3]. This chapter will focus on materials encountered by geophysicists (mud, snow, magma, etc.), although in most cases we will consider only suspensions of particles within an interstitial fluid without loss of generality. Other complex fluids such as polymeric liquids are rarely encountered in geophysics.

  1. Synthetic LDL as targeted drug delivery vehicle (United States)

    Forte, Trudy M.; Nikanjam, Mina


    The present invention provides a synthetic LDL nanoparticle comprising a lipid moiety and a synthetic chimeric peptide so as to be capable of binding the LDL receptor. The synthetic LDL nanoparticle of the present invention is capable of incorporating and targeting therapeutics to cells expressing the LDL receptor for diseases associated with the expression of the LDL receptor such as central nervous system diseases. The invention further provides methods of using such synthetic LDL nanoparticles.

  2. (BSA) nanoparticles as drug delivery vehicles

    African Journals Online (AJOL)



    Feb 19, 2008 ... method (Taguchi method with L16 orthogonal array robust design) was ... were considered as process parameters to be optimized. As the result of Taguchi analysis in this study, .... Sodium aside and all other chemicals were purchased from ..... determination of the optimal synthesis conditions for small and.

  3. Rheological Behavior of the Matrixes of Bauxite-Based Castables

    Institute of Scientific and Technical Information of China (English)

    Ye Fangbao; Rigaud M.; LIU Xinhong; ZHONG Xiangchong


    Rheology of castables is greatly affected and controlled by rheological behavior of their matrix. In this work, the rheological properties of bauxite-based castable matrix have been studied. The effects of super-fine silica and alumina addition, water/cement ratio, dispersants and bauxite particle-size on viscosity, shear rate and shear stress of the slurries have been investigated. Based on these results, the range of optimum composition of the matrix with good rheological behavior has been obtained.

  4. Formulation and evaluation of mefenamic acid emulgel for topical delivery


    Khullar, Rachit; Kumar, Deepinder; Seth, Nimrata; Saini, Seema


    Emulgels have emerged as a promising drug delivery system for the delivery of hydrophobic drugs. The objective of the study was to prepare emulgel of mefenamic acid, a NSAID, using Carbapol 940 as a gelling agent. Mentha oil and clove oil were used as penetration enhancers. The emulsion was prepared and it was incorporated in gel base. The formulations were evaluated for rheological studies, spreading coefficient studies, bioadhesion strength, skin irritation studies, in vitro release, ex viv...

  5. Rheology, oxygen transfer, and molecular weight characteristics of poly(glutamic acid) fermentation by Bacillus subtilis. (United States)

    Richard, Andrew; Margaritis, Argyrios


    Poly(glutamic acid) (PGA) is a water-soluble, biodegradable biopolymer that is produced by microbial fermentation. Recent research has shown that PGA can be used in drug delivery applications for the controlled release of paclitaxel (Taxol) in cancer treatment. A fundamental understanding of the key fermentation parameters is necessary to optimize the production and molecular weight characteristics of poly(glutamic acid) by Bacillus subtilis for paclitaxel and other applications of pharmaceuticals for controlled release. Because of its high molecular weight, PGA fermentation broths exhibit non-Newtonian rheology. In this article we present experimental results on the batch fermentation kinetics of PGA production, mass transfer of oxygen, specific oxygen uptake rate, broth rheology, and molecular weight characterization of the PGA biopolymer.

  6. Becker and Lomnitz rheological models: A comparison (United States)

    Mainardi, Francesco; Spada, Giorgio


    The viscoelastic material functions for the Becker and the Lomnitz rheological models, sometimes employed to describe the transient flow of rocks, are studied and compared. Their creep functions, which are known in a closed form, share a similar time dependence and asymptotic behavior. This is also found for the relaxation functions, obtained by solving numerically a Volterra equation of the second kind. We show that the two rheologies constitute a clear example of broadly similar creep and relaxation patterns associated with neatly distinct retardation spectra, for which analytical expressions are available.

  7. In situ rheology of yeast biofilms. (United States)

    Brugnoni, Lorena I; Tarifa, María C; Lozano, Jorge E; Genovese, Diego


    The aim of the present work was to investigate the in situ rheological behavior of yeast biofilms growing on stainless steel under static and turbulent flow. The species used (Rhodototula mucilaginosa, Candida krusei, Candida kefyr and Candida tropicalis) were isolated from a clarified apple juice industry. The flow conditions impacted biofilm composition over time, with a predominance of C. krusei under static and turbulent flow. Likewise, structural variations occurred, with a tighter appearance under dynamic flow. Under turbulent flow there was an increase of 112 μm in biofilm thickness at 11 weeks (p rheology and contribute to a thin body of knowledge about fungal biofilm formation.

  8. Rheology of the lithosphere: selected topics. (United States)

    Kirby, S.H.; Kronenberg, A.K.


    Reviews recent results concerning the rheology of the lithosphere with special attention to the following topics: 1) the flexure of the oceanic lithosphere, 2) deformation of the continental lithosphere resulting from vertical surface loads and forces applied at plate margins, 3) the rheological stratification of the continents, 4) strain localization and shear zone development, and 5) strain-induced crystallographic preferred orientations and anisotropies in body-wave velocities. We conclude with a section citing the 1983-1986 rock mechanics literature by category.-Authors

  9. Liquid rheology study on refined rapeseed oil

    Institute of Scientific and Technical Information of China (English)

    刘其梅; 罗迎社; 殷水平; 陈胜铭; 张党权; 彭万喜


    The rapeseed oil extracted from the mature seeds was purified by refining processing,and the rheological characteristic analysis of the viscosity and dynamic shear rate at gradient temperatures was made.The result shows that at 20,40,60 and 80 ℃ respectively,when the shear rate gradually rises,the torque increases accordingly but its viscosity does not vary distinctly.The result suggests that when rapeseed oil is used as the raw of edible oils and industries,the working procedures at high temperature will not influence its rheological characteristic distinctly.

  10. Dislocation evolution with rheological forming of metal

    Institute of Scientific and Technical Information of China (English)


    It is known that some internal defects exist in metal materials. Preliminary attempt to relate dislo cation evolution with metal rheological forming was done. By the attempt, it is learned that the evolution of dislocation density p( x, y, t ) is essentially the change of n independent internal variables qα (α = 1, 2, …n ) with material. The preliminary research in theory and experiments showed that dislocations piling-up could be avoided. One can improve the internal microstructure and mechanical properties of products by rheological forming method.


    Institute of Scientific and Technical Information of China (English)

    何学秋; 周世宁; 林柏泉


    Coal and methane outburst is one of the harmful disasters in coal mines. We have studied the rheological properties of gaseous coal in laboratory and obtained its rheological fracture principle. This principle can better explain and describe the outburst mechanism of gaseous coal. Thereby a rheological hypothesis of coal and methane outburst is put forward in this paper.

  12. Advances and expectations of study on wood rheology

    Institute of Scientific and Technical Information of China (English)

    马远荣; 罗迎社; 李贤军


    By studying and summarizing the characteristics of wood rheology,the mathematic models of creep and mechano-sorptive creep of wood were analyzed.Rheology behaviors in process,especially drying stress and deformation set were discussed.Application of wood rheology in woodcraft process was elaborated and the research prospects and orientation were forecasted.

  13. Delivery presentations (United States)

    ... passage will take place depends on how your baby is positioned during delivery. The best position for the baby to be ... possible, but labor will generally take longer. After delivery, the baby's face or brow will be swollen and may ...

  14. Congestion avoidance and break scheduling within vehicle routing

    NARCIS (Netherlands)

    Kok, Adrianus Leendert


    Vehicle routing is a complex daily task for businesses such as logistic service providers and distribution firms. Planners have to assign many orders to many vehicles and, for each vehicle, assign a delivery sequence. The objective is to minimize total transport costs. These costs typically include

  15. Congestion avoidance and break scheduling within vehicle routing

    NARCIS (Netherlands)

    Kok, A.L.


    Vehicle routing is a complex daily task for businesses such as logistic service providers and distribution firms. Planners have to assign many orders to many vehicles and, for each vehicle, assign a delivery sequence. The objective is to minimize total transport costs. These costs typically include

  16. Microemulsion Based Transdermal Drug Delivery of Tea Tree Oil

    Directory of Open Access Journals (Sweden)

    Khokhra Sonia


    Full Text Available Psoriasis is an inflammatory and proliferate disease of skin that results in rapid turnover of skin cells. Tea tree oil (TTO is the essential oil steam-distilled from Melaleuca alternifolia, known for its antimicrobial, antifungal and anti-inflammatory properties. This oil is a mix of many terpenes and among them terpinen-4-ol is the main active component. The study aimed at formulating a microemulsion based transdermal drug delivery system for psoriasis. Microemulsions were formulated using 5% Tea tree oil, different concentrations of Polysorbate 80 as surfactant and Isopropyl Myristate and Isopropyl alcohol as cosurfactants. The formulations were characterized for pH, Droplet size, PDI, Viscosity and Surface morphology. The mean droplet size of the microemulsion was found in the range of 84-115 nm with a PDI of 0.764 indicating uniformity in the microemulsion. Rheological data was assessed for viscosity and microemulsions were found to be low viscosity system. The maximum terpinen-4-ol content observed was 1.68 µg/mg of microemulsion. The TEM images of the microemulsion depicted spherical shape and even boundary of the oil particles. The skin diffusion studies clearly depicted the enhanced ability of microemulsion to deliver the drugs through transdermal application. About 14.5% Tepinen-4-ol penetration was observed from the microemulsion. Skin irritation confirmed that levels up to 5% tea tree oil could be safely applied to the skin. The studies showed that microemulsion system of tea tree oil might be promising vehicles for the transdermal delivery for psoriasis.

  17. Polyester Dendrimers: Smart Carriers for Drug Delivery

    Directory of Open Access Journals (Sweden)

    Jean–d’Amour K. Twibanire


    Full Text Available Polyester dendrimers have been shown to be outstanding candidates for biomedical applications. Compared to traditional polymeric drug vehicles, these biodegradable dendrimers show excellent advantages especially as drug delivery systems because they are non-toxic. Here, advances on polyester dendrimers as smart carriers for drug delivery applications have been surveyed. Both covalent and non-covalent incorporation of drugs are discussed.

  18. Liposomal dry powders as aerosols for pulmonary delivery of proteins


    Lu, Dongmei; Hickey, Anthony J.


    The purpose of this research was to develop liposomal dry powder aerosols for protein delivery. The delivery of stable protein formulations is essential for protein subunit vaccine delivery, which requires local delivery to macrophages in the lungs. β-Glucuronidase (GUS) was used as a model protein to evaluate dry powder liposomes as inhaled delivery vehicles. Dimyristoyl phosphatylcholine:cholesterol (7∶3) was selected as the liposome composition. The lyophilization of liposomes, micronizati...

  19. Extracellular vesicles for drug delivery

    NARCIS (Netherlands)

    Vader, Pieter; Mol, Emma A; Pasterkamp, Gerard; Schiffelers, Raymond M


    Extracellular vesicles (EVs) are cell-derived membrane vesicles, and represent an endogenous mechanism for intercellular communication. Since the discovery that EVs are capable of functionally transferring biological information, the potential use of EVs as drug delivery vehicles has gained consider

  20. Transport analogy for segregation and granular rheology (United States)

    Liu, Siying; McCarthy, Joseph J.


    Here, we show a direct connection between density-based segregation and granular rheology that can lead to insight into both problems. Our results exhibit a transition in the rate of segregation during simple shear that occurs at I ˜0.5 and mimics a coincident regime change in flow rheology. We propose scaling arguments that support a packing fraction criterion for this transition that can both explain our segregation results as well as unify existing literature studies of granular rheology. By recasting a segregation model in terms of rheological parameters, we establish an approach that not only collapses results for a wide range of conditions, but also yields a direct relationship between the coordination number z and the segregation velocity. Moreover, our approach predicts the precise location of the observed regime change or saturation. This suggests that it is possible to rationally design process operating conditions that lead to significantly lower segregation extents. These observations can have a profound impact on both the study of granular flow or mixing as well as industrial practice.


    The solution rheology of different generations of hyperbranched polyesters in N-methyl-2- pyrrolidinone (NMP) solvent was examined in this study. The solutions exhibited Newtonian behavior over a wide range of polyester concentrations. Also, the relative viscosities of poly(amido...


    African Journals Online (AJOL)


    Dec 31, 2012 ... investigated as a function of volume fraction and strength of ... The scaling variable (ϕp/ϕpc-1), suggested in percolation theory to describe rheological .... be planned to explain the variation of the elastic module with the ...

  3. Morphology and rheology in filamentous cultivations. (United States)

    Wucherpfennig, T; Kiep, K A; Driouch, H; Wittmann, C; Krull, R


    Because of their metabolic diversity, high production capacity, secretion efficiency, and capability of carrying out posttranslational modifications, filamentous fungi are widely exploited as efficient cell factories in the production of metabolites, bioactive substances, and native or heterologous proteins, respectively. There is, however, a complex relationship between the morphology of these microorganisms, transport phenomena, the viscosity of the cultivation broth, and related productivity. The morphological characteristics vary between freely dispersed mycelia and distinct pellets of aggregated biomass, every growth form having a distinct influence on broth rheology. Hence, the advantages and disadvantages for mycelial or pellet cultivation have to be balanced out carefully. Because of the still inadequate understanding of the morphogenesis of filamentous microorganisms, fungal morphology is often a bottleneck of productivity in industrial production. To obtain an optimized production process, it is of great importance to gain a better understanding of the molecular and cell biology of these microorganisms as well as the relevant approaches in biochemical engineering. In this chapter, morphology and growth of filamentous fungi are described, with special attention given to specific problems as they arise from fungal growth forms; growth and mass transfer in fungal biopellets are discussed as an example. To emphasize the importance of the flow behavior of filamentous cultivation broths, an introduction to rheology is also given, reviewing important rheological models and recent studies concerning rheological parameters. Furthermore, current knowledge on morphology and productivity in relation to the environom is outlined in the last section of this review. Copyright 2010 Elsevier Inc. All rights reserved.


    Directory of Open Access Journals (Sweden)

    Aurelia Ionescu


    Full Text Available Chickpea proteins are used as ingredients in comminuted sausage products and many oriental textured foods. Rheological behaviour of chickpea protein concentrate was studied using a controlled stress rheometer. The protein dispersion prepared with phosphate buffer at pH 7.0 presented non-Newtonian shear thinning behaviour and rheological data well fitted to the Sisko, Carreau and Cross models. The viscoelastic properties of the chickpea protein suspensions were estimated by measuring the storage and loss moduli in oscillatory frequency conditions (0.1-10 Hz at 20°C. Moreover, thermally induced gelation of the chickpea proteins (16, 24 and 36% was studied at pH 7.0 and 4.5 in the temperature range 50 to 100oC and salt concentration ranging from 0 to 1 M. Gelling behaviour was quantified by means of dynamic rheological measurements. Gels formation was preceded by the decrease of storage modulus and loss moduli, coupled with the increase of the phase angle (delta. The beginning of thermal gelation was influenced by protein concentration, pH and salt level. In all studied cases, storage modulus increased rapidly in the temperature range 70-90°C. All rheological parameters measured at 90°C were significantly higher at pH 4.5 compared to pH 7.0.

  5. Aggregate of nanoparticles: rheological and mechanical properties

    Directory of Open Access Journals (Sweden)

    Wang Yu


    Full Text Available Abstract The understanding of the rheological and mechanical properties of nanoparticle aggregates is important for the application of nanofillers in nanocompoistes. In this work, we report a rheological study on the rheological and mechanical properties of nano-silica agglomerates in the form of gel network mainly constructed by hydrogen bonds. The elastic model for rubber is modified to analyze the elastic behavior of the agglomerates. By this modified elastic model, the size of the network mesh can be estimated by the elastic modulus of the network which can be easily obtained by rheology. The stress to destroy the aggregates, i.e., the yield stress (σy , and the elastic modulus (G' of the network are found to be depended on the concentration of nano-silica (ϕ, wt.% with the power of 4.02 and 3.83, respectively. Via this concentration dependent behavior, we can extrapolate two important mechanical parameters for the agglomerates in a dense packing state (ϕ = 1: the shear modulus and the yield stress. Under large deformation (continuous shear flow, the network structure of the aggregates will experience destruction and reconstruction, which gives rise to fluctuations in the viscosity and a shear-thinning behavior.


    The solution rheology of different generations of hyperbranched polyesters in N-methyl-2- pyrrolidinone (NMP) solvent was examined in this study. The solutions exhibited Newtonian behavior over a wide range of polyester concentrations. Also, the relative viscosities of poly(amido...

  7. Rheology and structure of milk protein gels

    NARCIS (Netherlands)

    Vliet, van T.; Lakemond, C.M.M.; Visschers, R.W.


    Recent studies on gel formation and rheology of milk gels are reviewed. A distinction is made between gels formed by aggregated casein, gels of `pure` whey proteins and gels in which both casein and whey proteins contribute to their properties. For casein' whey protein mixtures, it has been shown th

  8. Impact of Rheology on Meltblown Polymer Nanofibers (United States)

    Tan, Dawud H.; Ellison, Christopher J.; Bates, Frank S.; Macosko, Christopher W.


    Melt blowing, a commercialized polymer processing technique, is used to produce a majority of nonwoven fiber products. It utilizes a stream of hot air to attenuate an extruded polymer strand into a fiber that is typically larger than 1 μm in diameter. Recently, our group has demonstrated the capability of melt blowing various polymers into defect-free fibers with an average diameter of several hundred nanometers by using a lab scale melt blowing device designed after a typical commercial instrument. However, surface tension-driven instabilities are observed when the smallest fibers are generated, resulting in droplets dispersed in the fiber mat. We hypothesize that altering the rheological properties of polymer may either delay or suppress these instabilities. In this study, the rheology has been studied systematically by melt blowing bidisperse polymeric blends obtained by mixing low and high molecular weight polymer. The associated changes in the rheological properties and the effect of rheology on the average and the width of the fiber diameter distribution will be highlighted.

  9. Rheology and structure of milk protein gels

    NARCIS (Netherlands)

    Vliet, van T.; Lakemond, C.M.M.; Visschers, R.W.


    Recent studies on gel formation and rheology of milk gels are reviewed. A distinction is made between gels formed by aggregated casein, gels of `pure` whey proteins and gels in which both casein and whey proteins contribute to their properties. For casein' whey protein mixtures, it has been shown

  10. Rheological characterization of media containing Penicillium chrysogenum

    DEFF Research Database (Denmark)

    Pedersen, Annemarie Gade; Bundgaard-Nielsen, Mikael; Nielsen, Jens;


    Samples from fed-batch fermentations of Penicillium chrysogenum on complex medium are rheologically characterized. The behavior is well described by a power law model for which the parameters are estimates. Furthermore, two types of model media are characterized and compared with the real...

  11. Rheological evaluation of Prunus mume pulp

    Directory of Open Access Journals (Sweden)

    Ernesto Quast


    Full Text Available The rheological behaviour of mume pulp at 6, 7, 8 and 9 °Brix was investigated using a rotational viscometer at temperatures ranging from 15 to 75 °C. The rheological models of Herschel-Bulkley and Ostwald-Waele (Power Law were fitted to obtain the rheological parameters of the mume pulp. The product was described as time non-dependent and presented a viscosity of 1.9 Pa.s at 15 °C and 1.1°Pa.s at 65 and 75 °C for the 9 °Brix pulp. The pulp showed non-Newtonian behaviour and the Herschel-Bulkley model was used to describe this behaviour. The activation energy ranged from 6.6-10.6 kJ.mol-1 and the consistency index from 18.0-22.9 Pa.s n for the 9 °Brix pulp and 8.3-12.2 Pa.s n for the 8 °Brix pulp at temperatures varying from 15 to 75 °C. The models presented high correlation values for all the rheological data obtained in the present work.

  12. Abandoned vehicles

    CERN Multimedia

    Relations with the Host States Service


    The services in charge of managing the CERN site have recently noted an increase in the number of abandoned vehicles. This poses a risk from the point of view of safety and security and, on the eve of several important events in honour of CERN's fiftieth anniversary, is detrimental to the Organization's image. Owners of vehicles that have been left immobile for some time on the CERN site, including on the external car park by the flags, are therefore invited to contact the Reception and Access Control Service ( before 1st October 2004 and, where appropriate, move their vehicle to a designated long-term parking area. After this date, any vehicle whose owner has failed to respond to this request and which is without a number plate, has been stationary for several weeks or is out of service, may be impounded at the owner's risk and expense. Relations with the Host States Service Tel. 72848

  13. Atomic force microscopy for the examination of single cell rheology. (United States)

    Okajima, Takaharu


    Rheological properties of living cells play important roles in regulating their various biological functions. Therefore, measuring cell rheology is crucial for not only elucidating the relationship between the cell mechanics and functions, but also mechanical diagnosis of single cells. Atomic force microscopy (AFM) is becoming a useful technique for single cell diagnosis because it allows us to measure the rheological properties of adherent cells at any region on the surface without any modifications. In this review, we summarize AFM techniques for examining single cell rheology in frequency and time domains. Recent applications of AFM for investigating the statistical analysis of single cell rheology in comparison to other micro-rheological techniques are reviewed, and we discuss what specificity and universality of cell rheology are extracted using AFM.

  14. GNeosomes: Highly Lysosomotropic Nanoassemblies for Lysosomal Delivery. (United States)

    Wexselblatt, Ezequiel; Esko, Jeffrey D; Tor, Yitzhak


    GNeosomes, lysosomotropic lipid vesicles decorated with guanidinoneomycin, can encapsulate and facilitate the cellular internalization and lysosomal delivery of cargo ranging from small molecules to high molecular weight proteins, in a process that is exclusively dependent on cell surface glycosaminoglycans. Their cellular uptake mechanism and co-localization with lysosomes, as well as the delivery, release, and activity of internalized cargo, are quantified. GNeosomes are proposed as a universal platform for lysosomal delivery with potential as a basic research tool and a therapeutic vehicle.

  15. Influence of microemulsions on cutaneous drug delivery

    DEFF Research Database (Denmark)

    Kreilgaard, Mads


    In attempt to increase cutaneous drug delivery, microemulsion vehicles have been more and more frequently employed over recent years. Microemulsion formulations have been shown to be superior for both transdermal and dermal delivery of particularly lipophilic compounds, but also hydrophilic...... compounds appear to benefit from application in microemulsions compared to conventional vehicles, like hydrogels, emulsions and liposomes. The favourable drug delivery properties of microemulsions appear to mainly be attributed to the excellent solubility properties. However, the vehicles may also act...... as penetration enhancers depending on the oil/surfactant constituents, which involves a risk of inducing local irritancy. The correlation between microemulsion structure/composition and drug delivery potential is not yet fully elucidated. However, a few studies have indicated that the internal structure...

  16. The pickup and delivery problem with cross-docking opportunity

    DEFF Research Database (Denmark)

    Petersen, Hanne Løhmann; Røpke, Stefan


    In this paper, we consider the pickup and delivery problem with cross-docking opportunity (PDPCD). The problem arises from an industry application, and includes pickup requests, delivery requests, and pickup-and-delivery requests. Each pickup-and-delivery request can be served either as direct...... delivery by one truck, or by being picked up and transported to the cross-dock by one vehicle, and subsequently delivered at its final destination by another vehicle. Handling times at customers sites and terminal are given. A typical daily instance includes 500-1,000 requests. We solve the problem using...

  17. Role of Yield Stress in Magma Rheology (United States)

    Kurokawa, A.; Di Giuseppe, E.; Davaille, A.; Kurita, K.


    Magmas are essentially multiphase material composed of solid crystals, gaseous bubbles and silicate liquids. They exhibit various types of drastic change in rheology with variation of mutual volumetric fractions of the components. The nature of this variable rheology is a key factor in controlling dynamics of flowing magma through a conduit. Particularly the existence of yield stress in flowing magma is expected to control the wall friction and formation of density waves. As the volumetric fraction of solid phase increases yield stress emerges above the critical fraction. Several previous studies have been conducted to clarify this critical value of magmatic fluid both in numerical simulations and laboratory experiments ([Lejeune and Pascal, 1995], [Saar and Manga 2001], [Ishibashi and Sato 2010]). The obtained values range from 13.3 to 40 vol%, which display wide variation and associated change in rheology has not been clarified well. In this presentation we report physical mechanism of emergence of yield stress in suspension as well as the associated change in the rheology based on laboratory experiments using analog material. We utilized thermogel aqueous suspension as an analog material of multiphase magma. Thermogel, which is a commercial name for poly(N-isopropyl acrylamide) (PNIPAM) undergoes volumetric phase change at the temperature around 35C:below this temperature the gel phase absorbs water and swells while below this it expels water and its volume shrinks. Because of this the volumetric fraction of gel phase systematically changes with temperature and the concentration of gel powder. The viscosity measured at lower stress drastically decreases across this phase change with increasing temperature while the viscosity at higher stress does not exhibit large change across the transition. We have performed a series of rheological measurements focusing on the emergence of yield stress on this aqueous suspension. Since the definition of yield stress is not

  18. 基于分区的多配送中心多车型车辆调度问题与遗传算法设计%Multi-delivery Centre Multi-type Vehicle Scheduling Problem Based on the Partition and the Design of Genetic Algorithm

    Institute of Scientific and Technical Information of China (English)

    马宇红; 姚婷婷; 张浩庆


    A large scale multi-delivery centre multi-type vehicle scheduling problem is considered. Firstly, based on the method of gravity center partition, the multi-delivery centre multi-type vehicle scheduling problem is transformed into the single-delivery centre multi-type vehicle scheduling problem, the partition method is simple, and reduces the amount of computations. Then based on the minimum delivery cost, a mathematical model of multi-delivery centre multi-type vehicle scheduling problem is established; the model considers not only the basic transportation cost, but also the driver's salary expenses, including the basic wage and overtime pay. In the model of multi-delivery centre multi-type vehicle scheduling, one car is able to provide service for more customers, however a customer must be served only by one car. According these characteristics, a new chromosomal hybrid encoding scheme is put forward, and the techniques of segmented crossover and mutation is used, the method effectively retains the father's generation superiority of chromosome fragments, therefore remarkably improves the convergence speed of the genetic algorithm. The results of numerical simulation verify the feasibility and effectiveness of the algorithm.%研究大规模的多配送中心多车型车辆调度问题,首先基于配送中心几何重心分区方法将多配送中心多车型车辆调度问题转化为单配送中心多车型车辆调度问题,该分区方法简单、直观,大大降低了运算量.建立了一种基于完整配送费用的多配送中心多车型车辆调度问题的数学模型,配送费用在考虑基本运输费的基础上又引入了司机的工资支出,包括基本工资和加班费.在多配送中心多车型车辆调度模型中,一个配送中心的一辆车可以为多个客户服务,但一个客户只能由某个配送中心的一辆车提供服务.根据模型的这些特点,提出了一种新的多片段染色体混合编

  19. Hermes vehicle (United States)

    Cretenet, J. C.


    The presence of Europe in the future developments of spatial programs, which are foreseen, for the 1990s and further, needs the availability of vehicles, modules and all related technologies adapted to operational use of low earth orbit station. The manned HERMES vehicle shall be part of the in-orbit infrastructure realized either in the European context or in cooperation between Europe and the United States. The main mission for this vehicle will be to run a shuttle with the station that means transport and change of the crews, its safe return in abort condition and cargo transport of consumable and experimental equipment. Secondary missions could be servicing on automatic platform, making autonomous scientific experiments. Lastly, the vehicle, by means of its on-board propulsion capability, could be used to accomplish in-orbit tow and assembly missions. Studies which are undertaken now about the vehicle are devoted to the aerodynamic shape (research of a compromise between aerothermic and overall fitting), the system (functional architecture, ground and flight configuration); further works dealing with technology are presently on hand in the field of thermal protection, aerodynamics, power generation with a high massic yield.

  20. electric vehicle

    Directory of Open Access Journals (Sweden)

    W. R. Lee


    Full Text Available A major problem facing battery-powered electric vehicles is in their batteries: weight and charge capacity. Thus, a battery-powered electric vehicle only has a short driving range. To travel for a longer distance, the batteries are required to be recharged frequently. In this paper, we construct a model for a battery-powered electric vehicle, in which driving strategy is to be obtained such that the total travelling time between two locations is minimized. The problem is formulated as an optimization problem with switching times and speed as decision variables. This is an unconventional optimization problem. However, by using the control parametrization enhancing technique (CPET, it is shown that this unconventional optimization is equivalent to a conventional optimal parameter selection problem. Numerical examples are solved using the proposed method.

  1. Hybrid vehicles

    Energy Technology Data Exchange (ETDEWEB)

    West, J.G.W. [Electrical Machines (United Kingdom)


    The reasons for adopting hybrid vehicles result mainly from the lack of adequate range from electric vehicles at an acceptable cost. Hybrids can offer significant improvements in emissions and fuel economy. Series and parallel hybrids are compared. A combination of series and parallel operation would be the ideal. This can be obtained using a planetary gearbox as a power split device allowing a small generator to transfer power to the propulsion motor giving the effect of a CVT. It allows the engine to run at semi-constant speed giving better fuel economy and reduced emissions. Hybrid car developments are described that show the wide range of possible hybrid systems. (author)

  2. Rheological behaviour of heated potato starch dispersions (United States)

    Juszczak, L.; Witczak, M.; Ziêba, T.; Fortuna, T.


    The study was designed to investigate the rheological properties of heated potato starch dispersions. Water suspensions of starch were heated at 65, 80 or 95°C for 5, 15, 30 or 60 min. The dispersions obtained were examined for granule size distribution and rheology. It was found that the starch dispersions significantly differed in both respects. The mean diameters of starch granules were largest for the dispersion heated at 65°C and smallest for that heated at 95°C. As the heating temperature was raised, the yield stresses and consistency coefficients decreased, while the flow behaviour indexes and Casson plastic viscosities increased. There were also differences in the viscoelastic properties of the dispersions: for those heated at 65°C the storage and loss moduli increased with heating time whereas for those heated at 80°C both moduli decreased.

  3. Colony Rheology: Active Arthropods Generate Flows (United States)

    Daniels, Karen; Mann, Michael; Charbonneau, Patrick


    Hydrodynamic-like flows are observed in biological systems as varied as bacteria, insects, birds, fish, and mammals. Both the phenomenology (e.g. front instabilities, milling motions) and the interaction types (hydrodynamic, direct contact, psychological, excluded-volume) strongly vary between systems, but a question common to all of them is to understand the role of particle-scale fluctuations in controlling large-scale rheological behaviors. We will address these questions through experiments on a new system, Tyrolichus casei (cheese mites), which live in dense, self-mixing colonies composed of a mixture of living mites and inert flour/detritus. In experiments performed in a Hele-Shaw geometry, we observe that the rheology of a colony is strongly dependent on the relative concentration of active and inactive particles. In addition to spreading flows, we also observe that the system can generate convective circulation and auto-compaction.

  4. Introduction to Rheology for Ultrasonic Engineers (United States)

    Ueda, Takanobu


    Here, I introduce the fundamental concept and methodology of rheology measurement especially to researchers in the field of ultrasonic engineering. Althogh we consider the material as fluid and characterize it in terms of viscosity accompanied by its complex part representing elasticity, ultrasonic spectroscopy regards the material as solid with elasticity, which determines ultrasonic velocity. Although these two research fields have contrary viewpoints, they share the purpose of the study, that is, to characterize the mechanical properties of the material as a function of frequency or shear rate and to reveal its mechanism and structure at the molecular level. In this paper, I show the basic methods of rheology measurement and analysis in relation to ultrasonic technology.

  5. Electric-Drive Vehicles

    Energy Technology Data Exchange (ETDEWEB)

    Septon, Kendall K [National Renewable Energy Laboratory (NREL), Golden, CO (United States)


    Electric-drive vehicles use electricity as their primary fuel or to improve the efficiency of conventional vehicle designs. These vehicles can be divided into three categories: Hybrid electric vehicles (HEVs), Plug-in hybrid electric vehicles (PHEVs), All-electric vehicles (EVs). Together, PHEVs and EVs can also be referred to as plug-in electric vehicles (PEVs).

  6. Rheological evaluation of pretreated cladding removal waste

    Energy Technology Data Exchange (ETDEWEB)

    McCarthy, D.; Chan, M.K.C.; Lokken, R.O.


    Cladding removal waste (CRW) contains concentrations of transuranic (TRU) elements in the 80 to 350 nCi/g range. This waste will require pretreatment before it can be disposed of as glass or grout at Hanford. The CRW will be pretreated with a rare earth strike and solids removal by centrifugation to segregate the TRU fraction from the non-TRU fraction of the waste. The centrifuge centrate will be neutralized with sodium hydroxide. This neutralized cladding removal waste (NCRW) is expected to be suitable for grouting. The TRU solids removed by centrifugation will be vitrified. The goal of the Rheological Evaluation of Pretreated Cladding Removal Waste Program was to evaluate those rheological and transport properties critical to assuring successful handling of the NCRW and TRU solids streams and to demonstrate transfers in a semi-prototypic pumping environment. This goal was achieved by a combination of laboratory and pilot-scale evaluations. The results obtained during these evaluations were correlated with classical rheological models and scaled-up to predict the performance that is likely to occur in the full-scale system. The Program used simulated NCRW and TRU solid slurries. Rockwell Hanford Operations (Rockwell) provided 150 gallons of simulated CRW and 5 gallons of simulated TRU solid slurry. The simulated CRW was neutralized by Pacific Northwest Laboratory (PNL). The physical and rheological properties of the NCRW and TRU solid slurries were evaluated in the laboratory. The properties displayed by NCRW allowed it to be classified as a pseudoplastic or yield-pseudoplastic non-Newtonian fluid. The TRU solids slurry contained very few solids. This slurry exhibited the properties associated with a pseudoplastic non-Newtonian fluid.

  7. Rheology, microrheology and structure of soft materials (United States)

    Oppong, Felix K.

    We study the relationship between the bulk rheological properties and the micron-scale structure and rheology of different types of soft materials. The materials studied are Laponite, a colloidal clay suspension; Carbopol, a dispersion of microgel particles; hydroxyethyl cellulose, a linear polymer solution; and hydrophobically modified hydroxyethyl cellulose, an associative polymer. Bulk properties are measured using conventional shear rheometry. The micron-scale measurements are performed using techniques based on multiple particle tracking and dynamic light scattering. From the thermal motion of suspended tracer particles, we obtain information about the local structure and viscoelastic properties of the materials. We investigate the evolution of Laponite from a liquid to a gel and find that the process is length-scale dependent. We study the properties of Carbopol as a function of microgel concentration and find that as concentration increases, a jamming transition occurs which is related to the onset of yield stress on the bulk scale. We compare the viscoelastic properties of hydroxyethylcellulose and its associative derivative and observe that the hydrophobic interactions in the latter lead to much slower dynamics than in the unmodified polymer. A study of the stress relaxation in hydroxyethylcellulose showed that it depended on both the wait time after the application and removal of a large strain and on the type and magnitude of the deformation applied. Our work exploits the unique ability of microrheological techniques to probe both the rheology and structure of soft materials on the microscopic scale, which enables a better understanding of the relationship between bulk scale properties and microscopic structure in these systems. Keywords. Rheology, microrheology, soft materials, particle tracking, dynamic light scattering, viscoelasticity, yield stress, gelation, polymers.

  8. Rheology and structural arrest of casein suspensions


    Dahbi, Louisa; Alexander, M.; Trappe, Véronique; Dhont, J. K. G.; Schurtenberger, Peter


    The rheology of milk powder suspensions is investigated up to very high concentrations, where structural arrest occurs. The main component of the milk powder investigated is casein, so that the suspensions can be regarded as casein suspensions. Four concentration regimes are identified. For effective casein volume fractions less than 0.54 the concentration dependence of the zero-shear viscosity is similar to that of hard-sphere suspensions. However, due to the elastic deformation of the casei...

  9. Forceps Delivery (United States)

    ... in place to control the advance of your baby's head. Forceps deliveries aren't always successful. If your health care ... com. Accessed June 12, 2015. You and your baby: Prenatal care, labor and delivery, and postpartum care. Washington, D.C.: The American ...


    Directory of Open Access Journals (Sweden)

    Tamara de Souza Jorge


    Full Text Available Avocado oil is rich in bioactive compounds, which can improve human health by acting as an antioxidant. It may be extracted from different varieties of avocado, such as Margarida and Hass varieties, each of them with particular characteristics. Aiming to evaluate the differences between them, avocado fruits and pulps from these were analyzed according to their physicochemical characteristics. After extracted, the oils had their bioactive characteristics studied and rheological behavior determined through a rotational rheometer. They were then compared to commercial avocado oil. The fruits of Margarida variety had greater size, higher weight (664.51 g, and higher pulp yield (72.19% than Hass variety, which showed higher lipid content (65.29 g/100 g dry basis. The commercial oil showed less primary oxidative degradation, whereas Margarida variety had a lower level of secondary degradation products as well as a higher content of bioactive compounds, such as phytosterols (999.60 mg/kg and tocopherols (36.73 mg/kg. The rheological behaviors of both oils were appropriately described through Newton model, with R2 > 0.999 for all temperatures. By an Arrhenius type equation, it was verified that Hass's rheological parameters are more influenced by temperature than Margarida and commercial oil, presenting activation energy of 33.6 kJ/mol.

  11. Evolution of the rheological structure of Mars (United States)

    Azuma, Shintaro; Katayama, Ikuo


    The evolution of Mars has been greatly influenced by temporal changes in its rheological structure, which may explain the difference in tectonics between Mars and Earth. Some previous studies have shown the rheological structures of Mars calculated from the flow law of rocks and the predicted thermal structure. However, the Peierls mechanism, which is the dominant deformation mechanism at relatively low temperature, and the evolution of water reservoirs on Mars were not considered in such studies. In this paper, we apply the Peierls mechanism to refine the rheological structure of Mars to show a new history of the planet that considers the most recent reports on its evolution of water reservoirs. Considering the Peierls creep and the evolution of water reservoirs, we attempt to explain why the tectonics of Mars is inactive compared with that of Earth. On early Mars, the lithospheric thickness inferred from the brittle-ductile transition was small, and the lithospheric strength was low ( 200-300 MPa) under wet conditions at 4 Gya. This suggests that plate boundaries could have developed on the early "wet" Mars, which is a prerequisite for the operation of plate tectonics. Our results also imply that the lithospheric strength had significantly increased in the Noachian owing to water loss. Therefore, plate tectonics may have ceased or could no longer be initiated on Mars. At the least, the tectonic style of Mars would have dramatically changed during the Noachian.[Figure not available: see fulltext.

  12. Rheology of nanocrystalline cellulose aqueous suspensions. (United States)

    Shafiei-Sabet, Sadaf; Hamad, Wadood Y; Hatzikiriakos, Savvas G


    The rheological properties and microstructure of nanocrystalline cellulose (NCC) aqueous suspensions have been investigated at different concentrations. The suspension is isotropic up to 3 wt %, and phase separates to liquid crystalline and isotropic domains at higher concentrations where the samples exhibit a fingerprint texture and the viscosity profile shows a three-region behavior, typical of liquid crystals. The suspension behaves as a rheological gel at even higher concentrations where the viscosity profile shows a single shear thinning behavior over the whole range of shear rates investigated. The effects of ultrasound energy and temperature on the rheological properties and structure of these suspensions were studied using polarized optical microscopy and rheometry. Our results indicate that the amount of applied ultrasound energy affects the microstructure of the suspensions and the pitch of the chiral nematic domains. The viscosity profile is changed significantly at low shear rates, whereas the viscosity of biphasic suspensions at intermediate and high shear rates decreased with increasing temperature. This suggests that, between 30 and 40 °C, structural rearrangement takes place. At higher concentrations of about 10 wt %, the temperature has no significant effect on viscosity; however, a marked increase in viscosity has been observed at around 50 °C. Finally, the Cox-Merz rule was found to fail after a critical concentration, thereby implying significant structural formation. This critical concentration is much higher for sonicated compared to unsonicated suspensions.

  13. Rheological, adhesive and release characterisation of semisolid Carbopol/tetraglycol systems. (United States)

    Bonacucina, Giulia; Cespi, Marco; Misici-Falzi, Monica; Palmieri, Giovanni F


    Gels dosage forms are successfully used as drug delivery systems considering their ability to control drug release and to protect medicaments from an hostile environment. This study deals with the gelation properties of Carbopol 971 e 974 polymeric systems in tetraglycol, a water-miscible cosolvent. In this paper, the attention was noted of the thickening properties of the different Carbopol in tetraglycol solvent at increasing temperatures, in order to obtain gels avoiding neutralisation and, at the same time, to make possible the dissolution in these gels of insoluble or poorly soluble water drugs. Samples were prepared by simply dispersing different Carbopols amount (0.5-4%) were added to tetraglycol and different systems were prepared at room temperature and by heating at 70 degrees C. All these systems were then characterised rheologically. Frequency sweep, creep-recovery, temperature sweep and time sweep analyses outlined that Carbopol 971 and 974 in tetraglycol gave rise after heating to gels with satisfactory rheological behaviour: the elastic modulus was greater than the viscous one and a remarkable elastic character was found to be present. Systems obtained by heating procedure were examined also from a mechanical point of view using a texture profile analysis. Besides, being Carbopols well known mucoadhesive polymers, gels adhesive properties were also studied using the ex vivo method. Texture and adhesion characterisation confirmed rheological results pointing out a certain greater elasticity and adhesiveness of Carbopol 974 systems. Then, the possible cutaneous irritation was also tested using the in vivo method (Draize test). No signs of cutaneous irritation were obtained for all the samples that were analysed. After rheological and mucoadhesive properties were set, paracetamol as a model drug was inserted in the composition of the gels and the release characteristics were defined. Dissolution tests pointed out the greater release control properties

  14. Rheological Predictions of Network Systems Swollen with Entangled Solvent (United States)


    solvent was previously studied experimentally. In this article, we use the discrete slip-link model to predict its linear and nonlinear rheology ...Model parameters are obtained from the dynamic modulus data of pure solvent. Network rheology predictions also require an estimate of the fraction and...Triangle Park, NC 27709-2211 rheology ;polymer properties;gels, networks;mathematical modeling;multiscale modeling REPORT DOCUMENTATION PAGE 11. SPONSOR

  15. Rheological properties of novel thermo-responsive polycarbonates aqueous solutions

    Institute of Scientific and Technical Information of China (English)

    王月霞; 谭业邦; 黄晓玲


    Thermo-responsive multiblock polycarbonates were facilely synthesized by covalently binding poly(ethylene glycol)(PEG) and poly(propylene glycol)(PPG) blocks,using triphosgene as coupling agent and pyridine as catalyst.The aqueous solutions of thermo-responsive polycarbonates were investigated by rheological measurements.Steady-state shear measurements reveal that the polycarbonate solutions exhibit shear-thinning behavior and the hydrophilic content has a pronounced effect on the flow behavior of the polycarbonates aqueous solutions.The shear viscosity decreases with increasing poly(ethylene oxide)(PEO) composition.The increase of viscosity with increasing concentration is probably attributed to the formation of stronger network owing to interchain entanglement of PEO block at higher concentration.When the flow curves are fitted to the power law model,flow index is obtained to be less than 1,as exhibiting typical pesudoplastic fluid.The viscoelastic properties of the system also show close dependence on the composition of polycarbonates.Temperature sweep confirms that the multiblock polycarbonates exhibit thermo-responsive properties.For 7% aqueous solution of polycarbonate with composition ratio of EO to PO of 1/1,the sol-gel transition occurs at 37 ℃,which makes the system suitable as an injectable drug delivery system.

  16. FedEx Express Gasoline Hybrid Electric Delivery Truck Evaluation: 12-Month Report

    Energy Technology Data Exchange (ETDEWEB)

    Barnitt, R.


    This report summarizes the data obtained in a 12-month comparison of three gasoline hybrid electric delivery vehicles with three comparable diesel vehicles. The data show that there was no statistical difference between operating cost per mile of the two groups of vehicles. As expected, tailpipe emissions were considerably lower across all drive cycles for the gHEV than for the diesel vehicle.

  17. FedEx Express Gasoline Hybrid Electric Delivery Truck Evaluation: 12-Month Report

    Energy Technology Data Exchange (ETDEWEB)

    Barnitt, R.


    This report summarizes the data obtained in a 12-month comparison of three gasoline hybrid electric delivery vehicles with three comparable diesel vehicles. The data show that there was no statistical difference between operating cost per mile of the two groups of vehicles. As expected, tailpipe emissions were considerably lower across all drive cycles for the gHEV than for the diesel vehicle.

  18. Post-seismic stress relaxation with a linear transient rheology

    Directory of Open Access Journals (Sweden)

    Antonio Piersanti


    Full Text Available We performed an analysis of post-seismic stress relaxation, taking into account generalized linear rheologies. We compared the stress field (and its derived functions obtained with a classical Maxwell rheology with that obtained with a transient Burgers body. From a set of synthetic case studies, we have revealed quantitative and qualitative differences both in relaxation times and in local stress values when a transient rheology is introduced. As a practical application, we modeled the time evolution of the Coulomb failure function following the 2009 L'Aquila earthquake, and we show that a transient rheology can lead to non-monotonic time dependence.

  19. Smart gelation of chitosan solution in the presence of NaHCO3 for injectable drug delivery system. (United States)

    Liu, Li; Tang, Ximin; Wang, Yuanyuan; Guo, Shengrong


    In situ gelling systems are attractive as injectable vehicles for drug delivery. The present work described a novel gelation process of acidic chitosan solution in the presence of sodium bicarbonate (NaHCO(3)). The NaHCO(3) concentration played an important role in this gelling system. When it came within the appropriate range, the chitosan/NaHCO(3) system would stay at sol state in certain condition and showed sol-gel transition from the top to the bottom after heating. The rheological properties of the gelling system, as well as the morphology and erosion behavior of the formed chitosan hydrogels were evaluated as a function of the NaHCO(3) concentration in sols. The hydrogels showed porous morphologies with some diversification depending on the NaHCO(3) concentration, which also affected their erosion behaviors and drug release rates. Moreover, the gelation mechanism of such chitosan/NaHCO(3) system was studied and proposed as the formation of three-dimensional chitosan network with physical junctions thanks to the deprotonation of -NH(3)(+) in chitosan accompanying with the gradual neutralization between HCO(3)(-) and acid. In vivo gelation test was also performed by the dorsal subcutaneous injection of chitosan/NaHCO(3) solution in rat. The formation of in situ gels suggested such system promising applications in injectable drug delivery system.

  20. 基于软时间窗的产品配送与安装相分离的车辆调度优化%Optimization for vehicle routeing with separated delivery and installation of products based on soft time windows

    Institute of Scientific and Technical Information of China (English)

    庞海军; 丁以中


    In order to satisfy the unique need of logistics in electronics industry, a variant of the Vehicle Routeing Problem (VRP) is studied based on the unique characteristics of electronics industry. The synchronism of the delivery and installation of products is separated, and a Mixed-Integer Nonlinear Programming (MINP) model is presented to minimize the traveling time of delivery and installation, which is the optimization model of VRP for delivery and installation based on soft time windows. Comparative analysis of the results illustrates the feasibility and effectiveness of the hierarchical approach and Genetic Algorithm (GA). The method can improve the efficiency of logistics distribution, reduce the enterprises' logistics cost, and improve the service level.%为满足电子行业独特的物流配送需求,依据电子行业的特点,研究一种变形的车辆调度问题(Vehicle Routeing Problem,VRP).将产品的配送与安装的同步性进行分离,建立以最小配送和安装旅行时间为目标的混合整数非线性规划(Mixed-Integer Nonlinear Programming,MINP)模型,即基于软时间窗的配送和安装车辆调度优化模型.对算例计算结果的比较分析表明采用分层方法和遗传算法(Genetic Algorithm,GA)的可行性和有效性.该模型可以提高电子行业的物流配送效率,降低物流成本,提高服务水平.

  1. Changes and significance of coagulation function, hemodynamics and blood rheology in women with pregnancy induced hypertension

    Institute of Scientific and Technical Information of China (English)

    Bang-Zhi Zeng; Bo Zhang; Yu-Na Wang


    Objective:To observe the changes of coagulation function, hemodynamics and blood rheology in patients with pregnancy induced hypertension, and to explore its clinical significance. Methods: A total of 88 cases of women with pregnancy induced hypertension who were admitted in our hospital from July 2011 to February 2016 were selected as the research objects, at the same time, 90 normal pregnant women were selected as normal late pregnancy group. The coagulation parameters, hemodynamics, blood rheology indexes were detected in the two groups.Results:Before delivery, values of the PT and AT-Ⅲ in pregnancy induced hypertension group were significantly lower than those in the normal late pregnancy group, and the values of D-D and FIB were significantly higher than those in the normal late pregnancy group. After delivery, values of the PT and AT-Ⅲ in pregnancy induced hypertension group were significantly higher, and the FIB value was significantly lower, there were no significant differences between the two group. But the D-D value was still significantly higher than that in the normal late pregnancy group. The blood flow dynamics parameter in pregnancy induced hypertension group were significantly higher than that in the normal late pregnant group, the differences were statistically significant. The whole blood high and low shear viscosity, plasma viscosity, low shear reduction viscosity, hematocrit, erythrocyte deformation index, erythrocyte electrophoresis time and fibrinogen in pregnancy induced hypertension group were significantly higher than those in normal late pregnancy group.Conclusion:The blood indexes in patients with pregnancy induced hypertension showed a high coagulation state compared with the normal late pregnancy women. Timely detection of patients’ coagulation function, hemodynamics, and blood rheology indexes has important significance for the detection, auxiliary diagnosis and prevention of the disease.

  2. Rheological behavior of oxide nanopowder suspensions (United States)

    Cinar, Simge

    Ceramic nanopowders offer great potential in advanced ceramic materials and many other technologically important applications. Because a material's rheological properties are crucial for most processing routes, control of the rheological behavior has drawn significant attention in the recent past. The control of rheological behavior relies on an understanding of how different parameters affect the suspension viscosities. Even though the suspension stabilization mechanisms are relatively well understood for sub-micron and micron size particle systems, this knowledge cannot be directly transferred to nanopowder suspensions. Nanopowder suspensions exhibit unexpectedly high viscosities that cannot be explained with conventional mechanisms and are still a topic of investigation. This dissertation aims to establish the critical parameters governing the rheological behavior of concentrated oxide nanopowder suspensions, and to elucidate the mechanisms by which these parameters control the rheology of these suspensions. Aqueous alumina nanopowders were chosen as a model system, and the findings were extrapolated to other oxide nanopowder systems such as zirconia, yttria stabilized zirconia, and titania. Processing additives such as fructose, NaCl, HCl, NaOH, and ascorbic acid were used in this study. The effect of solids content and addition of fructose on the viscosity of alumina nanopowder suspensions was investigated by low temperature differential scanning calorimetry (LT-DSC), rheological, and zeta potential measurements. The analysis of bound water events observed in LT-DSC revealed useful information regarding the rheological behavior of nanopowder suspensions. Because of the significance of interparticle interactions in nanopowder suspensions, the electrostatic stabilization was investigated using indifferent and potential determining ions. Different mechanisms, e.g., the effect of the change in effective volume fraction caused by fructose addition and electrostatic

  3. Statistical Characterization of Medium-Duty Electric Vehicle Drive Cycles; NREL (National Renewable Energy Laboratory)

    Energy Technology Data Exchange (ETDEWEB)

    Prohaska, R.; Duran, A.; Ragatz, A.; Kelly, K.


    With funding from the U.S. Department of Energy’s Vehicle Technologies Office, the National Renewable Energy Laboratory (NREL) conducts real-world performance evaluations of advanced medium- and heavy-duty fleet vehicles. Evaluation results can help vehicle manufacturers fine-tune their designs and assist fleet managers in selecting fuel-efficient, low-emission vehicles that meet their economic and operational goals. In 2011, NREL launched a large-scale performance evaluation of medium-duty electric vehicles. With support from vehicle manufacturers Smith and Navistar, NREL research focused on characterizing vehicle operation and drive cycles for electric delivery vehicles operating in commercial service across the nation.

  4. Using Tabu Search Heuristics in Solving the Vehicle Routing ...

    African Journals Online (AJOL)


    Routing Problem with Time Windows where the capacity of vehicle has been taken ... The optimal routes of the delivery of frozen chicken were found and it ... messages, people or goods from one place to another (Toth and Vigo, 2000). VRP.

  5. Rheological Properties of Aqueous Nanometric Alumina Suspensions

    Energy Technology Data Exchange (ETDEWEB)

    Li, Chuanping [Iowa State Univ., Ames, IA (United States)


    Colloidal processing is an effective and reliable approach in the fabrication of the advanced ceramic products. Successful colloidal processing of fine ceramic powders requires accurate control of the rheological properties. The accurate control relies on the understanding the influences of various colloidal parameters on the rheological properties. Almost all research done on the rheology paid less attention to the interactions of particle and solvent. However, the interactions of the particles are usually built up through the media in which the particles are suspended. Therefore, interactions of the particle with the media, the adsorbed layers on the particle surface, and chemical and physical properties of media themselves must influence the rheology of the suspension, especially for the dense suspensions containing nanosized particles. Relatively little research work has been reported in this area. This thesis addresses the rheological properties of nanometric alumina aqueous suspensions, and paying more attention to the interactions between particle and solvent, which in turn influence the particle-particle interactions. Dense nanometric alumina aqueous suspensions with low viscosity were achieved by environmentally-benign fructose additives. The rheology of nanometric alumina aqueous suspensions and its variation with the particle volume fraction and concentration of fructose were explored by rheometry. The adsorptions of solute (fructose) and solvent (water) on the nanometric alumina particle surfaces were measured and analyzed by TG/DSC, TOC, and NMR techniques. The mobility of water molecules in the suspensions and its variation with particle volume fractions and fructose additive were determined by the 17O NMR relaxation method. The interactions between the nanometric alumina particles in water and fructose solutions were investigated by AFM. The results indicated that a large number of water layers were physically bound on the particles

  6. Rheological Properties of Aqueous Nanometric Alumina Suspensions

    Energy Technology Data Exchange (ETDEWEB)

    Chuanping Li


    Colloidal processing is an effective and reliable approach in the fabrication of the advanced ceramic products. Successful colloidal processing of fine ceramic powders requires accurate control of the rheological properties. The accurate control relies on the understanding the influences of various colloidal parameters on the rheological properties. Almost all research done on the rheology paid less attention to the interactions of particle and solvent. However, the interactions of the particles are usually built up through the media in which the particles are suspended. Therefore, interactions of the particle with the media, the adsorbed layers on the particle surface, and chemical and physical properties of media themselves must influence the rheology of the suspension, especially for the dense suspensions containing nanosized particles. Relatively little research work has been reported in this area. This thesis addresses the rheological properties of nanometric alumina aqueous suspensions, and paying more attention to the interactions between particle and solvent, which in turn influence the particle-particle interactions. Dense nanometric alumina aqueous suspensions with low viscosity were achieved by environmentally-benign fructose additives. The rheology of nanometric alumina aqueous suspensions and its variation with the particle volume fraction and concentration of fructose were explored by rheometry. The adsorptions of solute (fructose) and solvent (water) on the nanometric alumina particle surfaces were measured and analyzed by TG/DSC, TOC, and NMR techniques. The mobility of water molecules in the suspensions and its variation with particle volume fractions and fructose additive were determined by the {sup 17}O NMR relaxation method. The interactions between the nanometric alumina particles in water and fructose solutions were investigated by AFM. The results indicated that a large number of water layers were physically bound on the particles

  7. Flexure and rheology of Pacific oceanic lithosphere (United States)

    Hunter, Johnny; Watts, Tony


    The idea of a rigid lithosphere that supports loads through flexural isostasy was first postulated in the late 19th century. Since then, there has been much effort to investigate the spatial and temporal variation of the lithosphere's flexural rigidity, and to understand how these variations are linked to its rheology. We have used flexural modelling to first re-assess the variation in the rigidity of oceanic lithosphere with its age at the time of loading, and then to constrain mantle rheology by testing the predictions of laboratory-derived flow laws. A broken elastic plate model was used to model trench-normal, ensemble-averaged profiles of satellite-derived gravity at the trench-outer rise system of circum-Pacific subduction zones, where an inverse procedure was used to find the best-fit Te and loading conditions. The results show a first-order increase in Te with plate age, which is best fit by the depth to the 400 ± 35°C plate-cooling isotherm. Fits to the observed gravity are significantly improved by an elastic plate that weakens landward of the outer rise, which suggests that bending-induced plate weakening is a ubiquitous feature of circum-Pacific subduction zones. Two methods were used to constrain mantle rheology. In the first, the Te derived by modelling flexural observations was compared to the Te predicted by laboratory-derived yield strength envelopes. In the second, flexural observations were modelled using elastic-plastic plates with laboratory-derived, depth-dependent yield strength. The results show that flow laws for low-temperature plasticity of dry olivine provide a good fit to the observations at circum-Pacific subduction zones, but are much too strong to fit observations of flexure in the Hawaiian Islands region. We suggest that this discrepancy can be explained by differences in the timescale of loading combined with moderate thermal rejuvenation of the Hawaiian lithosphere.

  8. The Nonlinear Rheology of Electrorheological Fluids (United States)

    Martin, James E.


    When a colloidal suspension is exposed to a uniaxial electric field the polarized particles chain along field lines causing a macroscopic "solidification" of the fluid, the basis of the so-called electrorheological (ER) effect. Likewise, in a rotating electric field particles form sheets in the plane of the field, which we call the rotary ER effect. Both of these fluids exhibit a nonlinear, shear thinning rheology, due to shear-induced structural relaxations. Because the fluid stress can be controlled by the applied field, a number of applications are possible, including electromechanical actuators, clutches, and active vibration dampers. To design these devices, and to develop effective control loop algorithms, it is necessary to understand the strongly nonlinear rheology of these fluids. We have used time-resolved, two-dimensional light scattering on a concentrated colloidal silica fluid in steady and oscillatory shear to demonstrate that the fragmentation and aggregation of chain-like particle microstructures is the cause of flow nonlinearities. We show that the light scattering is an indirect measure of the fluid stress. These observations form the basis of a kinetic chain model we developed to describe the nonlinear dynamics of the microstructures in ER fluids in nonstationary shear flows. Understanding the microstructural dynamics then leads us to a theory of the macroscopic rheology of these fluids in nonstationary, low Reynolds number flows. Finally, we have conducted extensive large-scale (1000-10000 particles) simulations of these fluids in steady and oscillatory shear, and will compare these results to theory and experiment.


    Institute of Scientific and Technical Information of China (English)

    DU Xue; XU Yuanze; QIAN Renyuan


    Rheological investigation on a series of unvulcanized polybutadiene elastomers of different processability has been carried out by means of a capillary extrusion rheometer. It is found that the processability of unvulcanized polybutadiene can be correlated with the occurrence of unsteadyflow and the wall stress, dependence of the dimensionless number e characterizing the entrance elongational elasticity which has been found to be sensitive to the branching structure and the molecular weight distribution of the samples. Interpretations based on the structural data of unvulcanized polybutadiene were discussed.


    Institute of Scientific and Technical Information of China (English)

    OU Yuchun; FANG Xiaoping; FENG Yupeng


    The relation between the rheological behavior and various interfacial properties of Kaolin rigid particle toughened polypropylene(PP/Kaolin) composites were studied by means of parallel-plate rheometer, melt flow rate apparatus, scanning electron microscopy (SEM) and other testing methods. The results show that addition of interfacial modifier to PP/Kaolin composites is advantageous to homogeneous dispersion of filler in PP matrix,formation of flexible interlayer between Kaolin particles and PP matrix and improvement of the melt processibility of the composites.


    Institute of Scientific and Technical Information of China (English)

    Zhen-zhong Yang; Yuan-ze Xu; De-lu Zhao


    The waterborne dispersions of epoxy resin were prepared by the phase inversion emulsification technique.Rheological behavior and its relationship with the structural change of the systems were studied. It was shown that the concentrated dispersions were highly viscoelastic and pseudoplastic, which was attributed to the formation of a physical network among the waterborne particles via hydrogen bond. The dilute dispersions were Newtonian fluids. The discrete clusters composed of small waterborne particles were found in diluted dispersions. With increasing solid content, there existed a structural transition via percolation through a cluster-cluster aggregation mode to form the physical network, which was qualitatively evidenced by the TEM morphologies.``


    Institute of Scientific and Technical Information of China (English)

    DONG Anjie; JING Xiabin; WANG Wei; FENG Zhiliu


    This paper presents our work on the rheological properties of the solution of polyaniline(PAn) in N-methyl-2-pyrrolidone (NMP). The results indicate that the solution's nonNewtonian property becomes more prominent with the increase in solution concentration,exhibiting the behavior of pseudo-plastic fluid. Besides, there is a critical concentration Cv(around 0.06 g/ml), beyond which the viscosity of the PAn/NMP solution takes a sudden increase. With temperature rising, both the viscosity and the thixotropy of the solution decrease, implying that there exist physical cross-linking interactions between the molecular chains in the solution.

  13. Crust rheology, slab detachment and topography (United States)

    Duretz, T.; Gerya, T. V.


    The collision between continents following the closure of an ocean can lead to the subduction of continental crust. The introduction of buoyant crust within subduction zones triggers the development of extensional stresses in slabs which eventually result in their detachment. The dynamic consequences of slab detachment affects the development of topography, the exhumation of high-pressure rocks and the geodynamic evolution of collision zones. We employ two-dimensional thermo-mechanical modelling in order to study the importance of crustal rheology on the evolution of spontaneous subduction-collision systems and the occurrence of slab detachment. The modelling results indicate that varying the rheological structure of the crust can results in a broad range of collisional evolutions involving slab detachment, delamination (associated to slab rollback), or the combination of both mechanisms. By enhancing mechanical coupling at the Moho, a strong crust leads to the deep subduction of the crust (180 km). These collisions are subjected to slab detachment and subsequent coherent exhumation of the crust accommodated by eduction (inversion of subduction sense) and thrusting. In these conditions, slab detachment promotes the development of a high (> 4.5 km) and narrow (delamination of the lithosphere, preventing slab detachment to occur. Further shortening leads to buckling and thickening of the crust resulting in the development of topographic bulging on the lower plate. Collisions involving rheologically layered crust are characterised by a decoupling level at mid-crustal depths. These initial condition favours the delamination of the upper crust as well as the deep subduction of the lower crust. These collisions are thus successively affected by delamination and slab detachment and both processes contribute to the exhumation of the subducted crust. A wide (> 200 km) topographic plateau develops as the results of the buoyant extrusion of the upper crust onto the foreland

  14. Rheological Behavior of the Guanidio Polyelectrolytes

    Institute of Scientific and Technical Information of China (English)

    ZHANG Yu-mei; JIANG Jian-ming; CHEN Yan-mo


    The rheological behavior of polyhexamethylene guanidine hydrochloride (PHGC) and polyethylene guanidine stearate (PHGS) has been investigated using the capillary rheometer. It is shown that the polyelectrolyte melts are non-Newtonian of shear. thinning fluid. The melt viscosity, the flow activation energy and the flow temperature are high even if the molecular weight is not high. The melting viscosity of PHGC is higher than that of PHGS at the same experimental conditions. By comparison with the case of PHGS the non-Newtonian index of PHGC is smaller, the flow activation energy and the flow temperature of PHGC are higher, which was caused by the difference in their molecular structure.

  15. The effects of cryopreservation on red blood cell rheologic properties

    NARCIS (Netherlands)

    Henkelman, Sandra; Lagerberg, Johan W. M.; Graaff, Reindert; Rakhorst, Gerhard; van Oeveren, Willem


    BACKGROUND: In transfusion medicine, frozen red blood cells (RBCs) are an alternative for liquid-stored RBCs. Little is known about the rheologic properties (i.e., aggregability and deformability) of thawed RBCs. In this study the rheologic properties of high-glycerol frozen RBCs and postthaw stored

  16. Electro-Rheological Effect of Liquid Crystalline Glycerin Derivative

    Institute of Scientific and Technical Information of China (English)

    N. Nakamura


    @@ 1Introduction Rheological property of a material is changed reversibly by an addition of electric field. The property is called electro-rheological (ER) effect, and the materials showed such an effect are named ER fluid in general.It is expected that the fluids are available for an application of mechanical fields like braking system, shock absorber one, and so on.


    Institute of Scientific and Technical Information of China (English)

    Wei Huang; Ying Huang; Yunzhao Yu


    Trimethylsilylated silica was synthesized through hydrolytic condensation of tetraethoxysilane followed by trimethylsilylation. Rheological properties of the silicone resin with trimethylsilylated silica as modifier were studied. It turned out that the particle size of silica was important to the rheological behavior of the modified resin. Trimethylsilylated silica of medium particle size shows the strongest tendency of forming physical network in the resin.

  18. Research on the rheological properties of pesticide suspension concentrate

    Institute of Scientific and Technical Information of China (English)

    谭成侠; 沈德隆; 翁建全; 陈庆悟; 刘会君; 袁其亮


    This study reports research on pesticide suspension rheology and a new rheological parameter, the relative value of approach, which has great advantage for judging the physical stability of a pesticide suspension concentrate. Experiments showed that the system can form stable dispersions when the value of the relative value of approach (Sr) is less than 0.1.

  19. Magneto-rheological defects and failures: A review (United States)

    Wahid, SA; Ismail, I.; Aid, S.; Rahim, MSA


    Magneto-rheological fluid is the colloidal suspension of micron sized magnetic particles in a carrier fluid where defects and failures occur at many circumstances. This paper presents a review on defects and failures of magneto-rheological fluid in engineering applications. The most significant defect is hard cake which developed due to re-dispersion difficulties of remnant particles magnetization, leaving the magneto-rheological fluid ineffective. Clumping effect on the other hand is a separation of carrier fluid from the magnetic particles when magneto-rheological fluid is being exposed to higher magnetic field for an extended period of time. As clumping occurred, it leads to Fluid Particle Separation (FPS) which is believed altering the strength distribution of magneto-rheological fluid and therefore reducing the squeezing force. Another significant failure is magnetic particles oxidation of the magneto-rheological fluid. This paper also will discuss on stability problems which is the most challenged issue in magneto-rheological fluid technology. With the comprehensive review in this paper, researcher can design materials of magneto-rheological fluid for better properties.

  20. Discussion on rheology in petroleum and nature gas teservoir stimulation

    Institute of Scientific and Technical Information of China (English)

    卢拥军; 梁冲; 胥云; 陈彦东


    Petroleum and nature gas not only are important resources,but also are important strategic materials of our country.All methods the enhancing the producing degree of petroleum and natural gas reservoir,increasing single well production and extending the stimulation period of validity are important stratagem for petroleum and natural gas exploitation.Fracturing and acidizing are the main methods for stimulation as well as one of representative examples of rheology theory application in engineering.Based on analysis of low permeability reservoir characteristics,the fracturing and acidizing stimulation principles and main controlling factors were discussed.And the mechanical characteristics,chemical reaction and rheological behavior in the stimulation process were reviewed.Furthermore research trends afterwards including the material and fluid rheology in oil and natural gas production process,the deep rock fracture initiation and extension rheology,and the fracturing and acidizing application rheology were also proposed in this paper.

  1. Melt rheology and its applications in the plastics industry

    CERN Document Server

    Dealy, John M


    This is the second edition of Melt Rheology and its Role in Plastics Processing, although the title has changed to reflect its broadened scope. Advances in the recent years in rheometer technology and polymer science have greatly enhanced the usefulness of rheology in the plastics industry. It is now possible to design polymers having specific molecular structures and to predict the flow properties of melts having those structures. In addition, rheological properties now provide more precise information about molecular structure. This book provides all the information that is needed for the intelligent application of rheology in the development of new polymers, the determination of molecular structure and the correlation of processability with laboratory test data. Theory and equations are limited to what is essential for the use of rheology in the characterization of polymers, the development of new plastics materials and the prediction of plastics processing behavior. The emphasis is on information that wil...

  2. Silica-Coated Liposomes for Insulin Delivery

    Directory of Open Access Journals (Sweden)

    Neelam Dwivedi


    Full Text Available Liposomes coated with silica were explored as protein delivery vehicles for their enhanced stability and improved encapsulation efficiency. Insulin was encapsulated within the fluidic phosphatidylcholine lipid vesicles by thin film hydration at pH 2.5, and layer of silica was formed above lipid bilayer by acid catalysis. The presence of silica coating and encapsulated insulin was identified using confocal and electron microscopy. The native state of insulin present in the formulation was evident from Confocal Micro-Raman spectroscopy. Silica coat enhances the stability of insulin-loaded delivery vehicles. In vivo study shows that these silica coated formulations were biologically active in reducing glucose levels.

  3. Structural rheology of a model ointment. (United States)

    Pena, L E; Lee, B L; Stearns, J F


    A model ointment consisting of white petrolatum, mineral oil and microcrystalline wax was studied using rheology, microscopy and thermal techniques. Rheograms studied over a temperature range of 25-40 degrees C indicated that the overall rheogram shape changed little as the temperature increased. However, two inflections gradually disappeared as the temperature increased. Thermal optical analysis showed that the temperature range over which these inflection disappeared correlated with the melting transition of the components forming the secondary structure. Another series of rheograms obtained from ointments with different combinations of the raw materials showed the rheology of the ointment is primarily controlled by the white petrolatum and mineral oil and that the microcrystalline wax acts to build-up the structure by incorporating itself into the existing white petrolatum structure. Thermal optical analysis of comelts of the raw materials proved that the ointment network structure is essentially a recombination of the naturally occurring components in differing ratios. The knowledge obtained from these studies is applied to a discussion of the thermal and mechanical stresses encountered in the filling operation.

  4. Rheology and dynamics of colloidal superballs. (United States)

    Royer, John R; Burton, George L; Blair, Daniel L; Hudson, Steven D


    Recent advances in colloidal synthesis make it possible to generate a wide array of precisely controlled, non-spherical particles. This provides a unique opportunity to probe the role that particle shape plays in the dynamics of colloidal suspensions, particularly at higher volume fractions, where particle interactions are important. We examine the role of particle shape by characterizing both the bulk rheology and micro-scale diffusion in a suspension of pseudo-cubic silica superballs. Working with these well-characterized shaped colloids, we can disentangle shape effects in the hydrodynamics of isolated particles from shape-mediated particle interactions. We find that the hydrodynamic properties of isolated superballs are marginally different from comparably sized hard spheres. However, shape-mediated interactions modify the suspension microstructure, leading to significant differences in the self-diffusion of the superballs. While this excluded volume interaction can be captured with a rescaling of the superball volume fraction, we observe qualitative differences in the shear thickening behavior of moderately concentrated superball suspensions that defy simple rescaling onto hard sphere results. This study helps to define the unknowns associated with the effects of shape on the rheology and dynamics of colloidal solutions.

  5. Ultrasound image velocimetry for rheological measurements (United States)

    Gurung, A.; Haverkort, J. W.; Drost, S.; Norder, B.; Westerweel, J.; Poelma, C.


    Ultrasound image velocimetry (UIV) allows for the non-intrusive measurement of a wide range of flows without the need for optical transparency. In this study, we used UIV to measure the local velocity field of a model drilling fluid that exhibits yield stress flow behavior. The radial velocity profile was used to determine the yield stress and the Herschel-Bulkley model flow index n and the consistency index k. Reference data were obtained using the conventional offline Couette rheometry. A comparison showed reasonable agreement between the two methods. The discrepancy in model parameters could be attributed to inherent differences between the methods, which cannot be captured by the three-parameter model used. Overall, with a whole flow field measurement technique such as UIV, we were able to quantify the complex rheology of a model drilling fluid. These preliminary results show that UIV can be used as a non-intrusive diagnostic for in situ, real-time measurement of complex opaque flow rheology.

  6. Dynamics and Rheology of Soft Colloidal Glasses

    KAUST Repository

    Wen, Yu Ho


    © 2015 American Chemical Society. The linear viscoelastic (LVE) spectrum of a soft colloidal glass is accessed with the aid of a time-concentration superposition (TCS) principle, which unveils the glassy particle dynamics from in-cage rattling motion to out-of-cage relaxations over a broad frequency range 10-13 rad/s < ω < 101 rad/s. Progressive dilution of a suspension of hairy nanoparticles leading to increased intercenter distances is demonstrated to enable continuous mapping of the structural relaxation for colloidal glasses. In contrast to existing empirical approaches proposed to extend the rheological map of soft glassy materials, i.e., time-strain superposition (TSS) and strain-rate frequency superposition (SRFS), TCS yields a LVE master curve that satis fies the Kramers-Kronig relations which interrelate the dynamic moduli for materials at equilibrium. The soft glassy rheology (SGR) model and literature data further support the general validity of the TCS concept for soft glassy materials.

  7. Study of rheological behaviour of wines (United States)

    Trávníček, Petr; Burg, Patrik; Krakowiak-Bal, Anna; Junga, Petr; Vítěz, Tomáš; Ziemiańczyk, Urszula


    This study deals with rheological properties of various wine varieties. Samples of the following wines were used for this experiment: André, Cabernet Moravia, Laurot, Saint Laurent, Gruner Veltliner, Pinot Blanc, Müller Thurgau, and Riesling Italico. These samples were obtained from wine produced from the grapes collected in the Czech Republic (Morava region, subregion Velke Pavlovice). In the first phase, the chemical composition of the samples was determined. The following chemical parameters were determined: total acidity, pH, content of the alcohol, reduced sugars, free SO2, total SO2, and volatile acids. In the second phase of the study, the physical properties of the samples were determined and the samples of the wines were subjected to rheological tests. These tests consisted in determination of apparent viscosity in relation to temperature, hysteresis loop tests, and apparent viscosity related to time. The dependence of the shear rate on the shear stress was described with the Herschel-Bulkley mathematical model. The experiment yielded the following findings: seven out of the eight samples behaved as non-Newtonian fluids at low temperature (5°C); non-Newtonian behaviour was changed into Newtonian at the temperature higher than 10°C; non-Newtonian behaviour was characterised as thixotropic behaviour; the degree of thixotropy is relatively small and reaches 1.85 Pa s-1 ml-1.

  8. Study of the rheological properties of oil

    Energy Technology Data Exchange (ETDEWEB)

    Jewulski, J.


    The author describes industrial research into the process of disturbing the thixotropic structure of oil in well L-3 during constant oil coagulation inside the ''Rheostat'' rotating cylindrical viscosity meter. This oil, containing paraffin, has a high viscosity and corresponds to the chemical classification for pseudo water plastic thixotropic flowing liquid. This research was conducted at temperatures of 15,20,25, and 30 degrees C. The final time period is determined for the disintegration of the oil structure, during which almost no indicator changes are detected by industrial metering devices. This process of disintegration was viewed by the author as a breakdown of the thixotropic structure during the given rate of coagulation. Metering results were approximated and found to be most significant in non-stationary processes over a relatively short period of time. The rheological curve is then often replaced by a straight angle. This article also examines certain factors in the transport of such oil and trunklines and the resulting effects upon that oil's rheological composition.

  9. Rheological changes in irradiated chicken eggs

    Energy Technology Data Exchange (ETDEWEB)

    Ferreira, Lucia F. S.; Del Mastro, Nelida L


    Pathogenic bacteria may cause foodborne illnesses. Humans may introduce pathogens into foods during production, processing, distribution and or preparation. Some of these microorganisms are able to survive conventional preservation treatments. Heat pasteurization, which is a well established and satisfactory means of decontamination/disinfection of liquid foods, cannot efficiently achieve a similar objective for solid foods. Extensive work carried out worldwide has shown that irradiation is efficient in eradicating foodborne pathogens like Salmonella spp. that can contaminate poultry products. In this work Co-60 gamma irradiation was applied to samples of industrial powder white, yolk and whole egg at doses between 0 and 25 kGy. Samples were rehydrated and the viscosity measured in a Brookfield viscosimeter, model DV III at 5, 15 and 25 degree sign C. The rheological behaviour among the various kinds of samples were markedly different. Irradiation with doses up to 5 kGy, known to reduced bacterial contamination to non-detectable levels, showed almost no variation of viscosity of irradiated egg white samples. On the other hand, whole or yolk egg samples showed some changes in rheological properties depending on the dose level, showing the predominance of whether polimerization or degradation as a result of the irradiation. Additionally, irradiation of yolk egg powder reduced yolk color as a function of the irradiation exposure implemented. The importance of these results are discussed in terms of possible industrial applications.

  10. Review Of Rheology Modifiers For Hanford Waste

    Energy Technology Data Exchange (ETDEWEB)

    Pareizs, J. M.


    As part of Savannah River National Laboratory (SRNL)'s strategic development scope for the Department of Energy - Office of River Protection (DOE-ORP) Hanford Tank Waste Treatment and Immobilization Plant (WTP) waste feed acceptance and product qualification scope, the SRNL has been requested to recommend candidate rheology modifiers to be evaluated to adjust slurry properties in the Hanford Tank Farm. SRNL has performed extensive testing of rheology modifiers for use with Defense Waste Processing Facility (DWPF) simulated melter feed - a high undissolved solids (UDS) mixture of simulated Savannah River Site (SRS) Tank Farm sludge, nitric and formic acids, and glass frit. A much smaller set of evaluations with Hanford simulated waste have also been completed. This report summarizes past work and recommends modifiers for further evaluation with Hanford simulated wastes followed by verification with actual waste samples. Based on the review of available data, a few compounds/systems appear to hold the most promise. For all types of evaluated simulated wastes (caustic Handford tank waste and DWPF processing samples with pH ranging from slightly acidic to slightly caustic), polyacrylic acid had positive impacts on rheology. Citric acid also showed improvement in yield stress on a wide variety of samples. It is recommended that both polyacrylic acid and citric acid be further evaluated as rheology modifiers for Hanford waste. These materials are weak organic acids with the following potential issues: The acidic nature of the modifiers may impact waste pH, if added in very large doses. If pH is significantly reduced by the modifier addition, dissolution of UDS and increased corrosion of tanks, piping, pumps, and other process equipment could occur. Smaller shifts in pH could reduce aluminum solubility, which would be expected to increase the yield stress of the sludge. Therefore, it is expected that use of an acidic modifier would be limited to concentrations that

  11. Rheology of Volatile-rich Crystal Mush (United States)

    Pistone, M.; Caricchi, L.; Ulmer, P.; Reusser, E.; Mancktelow, N.; Burlini, L.


    Magma batholiths are commonly highly crystalline (> 50 vol%; crystal mush, Bachmann and Bergantz, 2008a) and possible modes of mobilization and emplacement have been intensively discussed in the last decades. Recently, it has been proposed that a stiff mushy batholith must be reheated to mobilize; this produces a reduction in crystallinity that leads to an increase of the magma buoyancy (Burgisser and Bergantz, 2011). Another way of batholith mobilization in the crust can be caused by addition of volatiles (mainly H2O and CO2) released by ascending hydrous mafic magmas coming from the mantle (Bachmann and Bergantz, 2008b). The enrichment in volatiles induces a drastic decrease in the bulk viscosity of the granitic body and, thus, an evident change in the rheological properties of the batholith. The rheology of such very crystal-rich highly viscous systems is still a matter of debate. To provide some additional experimental constraints relevant to this discussion, we deformed hydrous (2.52 wt% H2O) haplogranitic magmas containing variable amounts of quartz crystals (from 55 to 65 vol%), and fixed volume of gas-pressurized CO2-bubbles (9-10 vol%), in simple shear using a HT-HP Paterson-type rock deformation apparatus. Strain rates ranging between 1•10-5 s-1 and 4•10-3 s-1 were applied at temperatures between 823 and 1023 K and constant confining pressure of 200-250 MPa (8-9 km depth). The results suggest that three-phase suspensions are characterized by strain rate-dependent rheology (non-Newtonian behavior). Two non-Newtonian regimes were observed: shear thinning (decrease of viscosity with increasing strain rate) and shear thickening (increase of viscosity with increasing strain rate). The first effect dominantly occurs because of crystal size reduction and shear localization, enhanced by the presence of gas bubbles in the weak shear bands. However, when the solid crystal framework induces an internal flow blockage due to crystal interlock, the second effect

  12. 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. (United States)

    Yang, Hu; Leffler, Christopher T


    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.

  13. Hydraulic Hybrid Parcel Delivery Truck Deployment, Testing & Demonstration

    Energy Technology Data Exchange (ETDEWEB)

    Gallo, Jean-Baptiste [Calstart Incorporated, Pasadena, CA (United States)


    Although hydraulic hybrid systems have shown promise over the last few years, commercial deployment of these systems has primarily been limited to Class 8 refuse trucks. In 2005, the Hybrid Truck Users Forum initiated the Parcel Delivery Working Group including the largest parcel delivery fleets in North America. The goal of the working group was to evaluate and accelerate commercialization of hydraulic hybrid technology for parcel delivery vehicles. FedEx Ground, Purolator and United Parcel Service (UPS) took delivery of the world’s first commercially available hydraulic hybrid parcel delivery trucks in early 2012. The vehicle chassis includes a Parker Hannifin hydraulic hybrid drive system, integrated and assembled by Freightliner Custom Chassis Corp., with a body installed by Morgan Olson. With funding from the U.S. Department of Energy, CALSTART and its project partners assessed the performance, reliability, maintainability and fleet acceptance of three pre-production Class 6 hydraulic hybrid parcel delivery vehicles using information and data from in-use data collection and on-road testing. This document reports on the deployment of these vehicles operated by FedEx Ground, Purolator and UPS. The results presented provide a comprehensive overview of the performance of commercial hydraulic hybrid vehicles in parcel delivery applications. This project also informs fleets and manufacturers on the overall performance of hydraulic hybrid vehicles, provides insights on how the technology can be both improved and more effectively used. The key findings and recommendations of this project fall into four major categories: -Performance, -Fleet deployment, -Maintenance, -Business case. Hydraulic hybrid technology is relatively new to the market, as commercial vehicles have been introduced only in the past few years in refuse and parcel delivery applications. Successful demonstration could pave the way for additional purchases of hydraulic hybrid vehicles throughout the

  14. Rheological properties of cupuassu and cocoa fats

    Directory of Open Access Journals (Sweden)

    Gioielli, L. A.


    Full Text Available Cocoa butter is an important ingredient in chocolate formulation as it dictates the main properties (texture, sensation in the mouth, and gloss. In the food industry, the texture of fat-containing products strongly depends on the macroscopic properties of the fat network formed within the finished product. Cupuassu ( Theobroma grandiflorum , Sterculiaceae is an Amazonian native fruit and the seeds can be used to derive a cocoa butter like product. In general, these fats are similar to those of cocoa, although they are different in some physical properties. The objective of this study was to analyze several properties of the cupuassu fat and cocoa butter (crystal formation at 25 ° C, rheological properties, and fatty acid composition and mixtures between the two fats (rheological properties, in order to understand the behavior of these fats for their use in chocolate products. Fat flow was described using common rheological models ( Newton , Power Law, Casson and Bingham plastic.La manteca de cacao es un ingrediente muy importante en la formulación de chocolates y es responsable de la mayor parte de sus propiedades (textura, palatibilidad y brillo. En la industria de alimentos, la textura de productos que contienen grasa depende enormemente de las propiedades macroscópicas de la red cristalina de la grasa en el producto final. El cupuaçu es una fruta nativa de la región amazónica y sus semillas pueden ser usadas para obtener una grasa semejante a la manteca de cacao. En general, esta grasa es similar a la manteca de cacao, pero difiere en algunas de sus propiedades fisicas . El objetivo de este estudio fue analizar algunas propiedades de la grasa de cupuaçu y de la manteca de cacao (formación de cristales a 25 °C, propiedades reológicas y composición en ácidos grasos y de algunas mezclas entre las dos grasas (propiedades reológicas, a fin de conocer el comportamiento de estas grasas para ser usadas en productos de la industria

  15. Rheology of Melt-bearing Crustal Rocks (United States)

    Rosenberg, C. L.; Medvedev, S.; Handy, M. R.


    A review and reinterpretation of previous experimental data on the deformation of melt-bearing crustal rocks (Rosenberg and Handy, 2005) revealed that the relationship of aggregate strength to melt fraction is non-linear, even if plotted on a linear ordinate and abscissa. At melt fractions, Φ 0.07, the dependence of aggregate strength on Φ is significantly greater than at Φ > 0.07. This melt fraction (Φ= 0.07) marks the transition from a significant increase in the proportion of melt-bearing grain boundaries up to this point to a minor increase thereafter. Therefore, we suggest that the increase of melt-interconnectivity causes the dramatic strength drop between the solidus and a melt fraction of 0.07. A second strength drop occurs at higher melt fractions and corresponds to the breakdown of the solid (crystal) framework, corresponding to the well-known "rheologically critical melt percentage" (RCMP; Arzi, 1978). Although the strength drop at the RCMP is about 4 orders of magnitude, the absolute value of this drop is small compared to the absolute strength of the unmelted aggregate, rendering the RCMP invisible in a linear aggregate strength vs. melt fraction diagram. Predicting the rheological properties and thresholds of melt-bearing crust on the basis of the results and interpretations above is very difficult, because the rheological data base was obtained from experiments performed at undrained conditions in the brittle field. These conditions are unlikely to represent the flow of partially melted crust. The measured strength of most of the experimentally deformed, partially-melted samples corresponds to their maximum differential stress, before the onset of brittle failure, not to their viscous strength during "ductile" (viscous) flow. To overcome these problems, we extrapolated a theoretically-derived flow law for partially melted granite deforming by diffusion-accommodated grain-boundary sliding (Paterson, 2001) and an experimentally-derived flow law for

  16. Shear History Extensional Rheology Experiment II (SHERE II) Microgravity Rheology with Non-Newtonian Polymeric Fluids (United States)

    Jaishankar, Aditya; Haward, Simon; Hall, Nancy Rabel; Magee, Kevin; McKinley, Gareth


    The primary objective of SHERE II is to study the effect of torsional preshear on the subsequent extensional behavior of filled viscoelastic suspensions. Microgravity environment eliminates gravitational sagging that makes Earth-based experiments of extensional rheology challenging. Experiments may serve as an idealized model system to study the properties of lunar regolith-polymeric binder based construction materials. Filled polymeric suspensions are ubiquitous in foods, cosmetics, detergents, biomedical materials, etc.

  17. Optimized vehicle scheduling and filling model based on effective space and integrated solving algorithm

    Institute of Scientific and Technical Information of China (English)

    ZHAO Peng; MU Xin; YAO Jin-hua; WANG Yong; YANG Xiu-tai


    We established an integrated and optimized model of vehicle scheduling problem and vehicle filling problem for solving an extremely complex delivery mode-multi-type vehicles, non-full loads, pickup and delivery in logistics and delivery system. The integrated and optimized model is based on our previous research result-effective space method. An integrated algorithm suitable for the integrated and optimized model was proposed and corresponding computer programs were designed to solve practical problems. The results indicates the programs can work out optimized delivery routes and concrete loading projects. The model and algorithm have many virtues and are valuable in practice.

  18. Improved Ant Colony Optimization for Seafood Product Delivery Routing Problem

    Directory of Open Access Journals (Sweden)

    Baozhen Yao


    Full Text Available This paper deals with a real-life vehicle delivery routing problem, which is a seafood product delivery routing problem. Considering the features of the seafood product delivery routing problem, this paper formulated this problem as a multi-depot open vehicle routing problem. Since the multi-depot open vehicle routing problem is a very complex problem, a method is used to reduce the complexity of the problem by changing the multi-depot open vehicle routing problem into an open vehicle routing problem with a dummy central depot in this paper. Then, ant colony optimization is used to solve the problem. To improve the performance of the algorithm, crossover operation and some adaptive strategies are used. Finally, the computational results for the benchmark problems of the multi-depot vehicle routing problem indicate that the proposed ant colony optimization is an effective method to solve the multi-depot vehicle routing problem. Furthermore, the computation results of the seafood product delivery problem from Dalian, China also suggest that the proposed ant colony optimization is feasible to solve the seafood product delivery routing problem.

  19. Attenuation of seismic waves and the universal rheological model of the Earth's mantle (United States)

    Birger, B. I.


    Analysis of results of laboratory studies on creep of mantle rocks, data on seismic wave attenuation in the mantle, and rheological micromechanisms shows that the universal, i.e., relevant to all time scales, rheological model of the mantle can be represented as four rheological elements connected in series. These elements account for elasticity, diffusion rheology, high temperature dislocation rheology, and low temperature dislocation rheology. The diffusion rheology element is described in terms of a Newtonian viscous fluid. The high temperature dislocation rheology element is described by the rheological model previously proposed by the author. This model is a combination of a power-law non-Newtonian fluid model for stationary flows and the linear hereditary Andrade model for flows associated with small strains. The low temperature dislocation rheology element is described by the linear hereditary Lomnitz model.

  20. Comparative costs and benefits of hydrogen vehicles

    Energy Technology Data Exchange (ETDEWEB)

    Berry, G.D. [Lawrence Livermore National Lab., CA (United States)


    The costs and benefits of hydrogen as a vehicle fuel are compared to gasoline, natural gas, and battery-powered vehicles. Costs, energy, efficiency, and tail-pipe and full fuel cycle emissions of air pollutants and greenhouse gases were estimated for hydrogen from a broad range of delivery pathways and scales: from individual vehicle refueling systems to large stations refueling 300 cars/day. Hydrogen production from natural gas, methanol, and ammonia, as well as water electrolysis based on alkaline or polymer electrolytes and steam electrolysis using solid oxide electrolytes are considered. These estimates were compared to estimates for competing fuels and vehicles, and used to construct oil use, air pollutant, and greenhouse gas emission scenarios for the U.S. passenger car fleet from 2005-2050. Fuel costs need not be an overriding concern in evaluating the suitability of hydrogen as a fuel for passenger vehicles. The combined emissions and oil import reduction benefits of hydrogen cars are estimated to be significant, valued at up to {approximately}$400/yr for each hydrogen car when primarily clean energy sources are used for hydrogen production. These benefits alone, however, become tenuous as the basis supporting a compelling rationale for hydrogen fueled vehicles, if efficient, advanced fossil-fuel hybrid electric vehicles (HEV`s) can achieve actual on-road emissions at or below ULEV standards in the 2005-2015 timeframe. It appears a robust rationale for hydrogen fuel and vehicles will need to also consider unique, strategic, and long-range benefits of hydrogen vehicles which can be achieved through the use of production, storage, delivery, and utilization methods for hydrogen which are unique among fuels: efficient use of intermittent renewable energy sources, (e,g, wind, solar), small-scale feasibility, fuel production at or near the point of use, electrolytic production, diverse storage technologies, and electrochemical conversion to electricity.