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Sample records for boronated liposome development

  1. Boronated liposome development and evaluation

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    Hawthorne, M.F. [Univ. of California, Los Angeles, CA (United States)

    1995-11-01

    The boronated liposome development and evaluation effort consists of two separate tasks. The first is the development of new boron compounds and the synthesis of known boron species with BNCT potential. These compounds are then encapsulated within liposomes for the second task, biodistribution testing in tumor-bearing mice, which examines the potential for the liposomes and their contents to concentrate boron in cancerous tissues.

  2. Boron-Containing Compounds for Liposome-Mediated Tumor Localization and Application to Neutron Capture Therapy

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    Hawthorne, M. Frederick [Univ. of California, Los Angeles, CA (United States)

    2005-04-07

    Medical application of boron neutron capture therapy (BNCT) has been significantly hindered by the slow development of boron drug-targeting methodologies for the selective delivery of high boron concentration sto malignant cells. We have successfully sought to fill this need by creating liposomes suitable as in vivo boron delivery vehicles for BNCT. Delivery of therapeutic quantities of boron to tumors in murine models has been achieved with small unilamellar boron-rich liposomes. Subsequently, attempts have been made to improve delivery efficiency of liposomes encapsulating boron-containing water-soluble species into their hollow core by incorporating lipophilic boron compounds as addenda to the liposome bilayer, incorporating boron compounds as structural components of the bilayer (which however, poses the risk of sacrificing some stability), and combinations thereof. Regardless of the method, approximately 90% of the total liposome mass remains therapeutically inactive and comprised of the vehicle's construction materials, while less than 5% is boron for neutron targeting. Following this laboratory's intensive study, the observed tumor specificity of certain liposomes has been attributed to their diminutive size of these liposomes (30-150 nm), which enables these small vesicles to pass through the porous, immature vasculature of rapidly growing tumor tissue. We surmised that any amphiphilic nanoparticle of suitable size could possess some tumor selectivity. Consequently, the discovery of a very boron-rich nanoparticle delivery agent with biodistribution performance similar to unilamellar liposomes became one of our goals. Closomers, a new class of polyhedral borane derivatives, attracted us as an alternative BNCT drug-delivery system. We specifically envisioned dodeca (nido-carboranyl)-substituted closomers as possibly having a great potential role in BNCT drug delivery. They could function as extraordinarily boron-rich BNCT drugs since they are

  3. Therapeutic efficacy of boron neutron capture therapy mediated by boron-rich liposomes for oral cancer in the hamster cheek pouch model.

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    Heber, Elisa M; Hawthorne, M Frederick; Kueffer, Peter J; Garabalino, Marcela A; Thorp, Silvia I; Pozzi, Emiliano C C; Monti Hughes, Andrea; Maitz, Charles A; Jalisatgi, Satish S; Nigg, David W; Curotto, Paula; Trivillin, Verónica A; Schwint, Amanda E

    2014-11-11

    The application of boron neutron capture therapy (BNCT) mediated by liposomes containing (10)B-enriched polyhedral borane and carborane derivatives for the treatment of head and neck cancer in the hamster cheek pouch oral cancer model is presented. These liposomes are composed of an equimolar ratio of cholesterol and 1,2-distearoyl-sn-glycero-3-phosphocholine, incorporating K[nido-7-CH3(CH2)15-7,8-C2B9H11] (MAC) in the bilayer membrane while encapsulating the hydrophilic species Na3[ae-B20H17NH3] (TAC) in the aqueous core. Unilamellar liposomes with a mean diameter of 83 nm were administered i.v. in hamsters. After 48 h, the boron concentration in tumors was 67 ± 16 ppm whereas the precancerous tissue contained 11 ± 6 ppm, and the tumor/normal pouch tissue boron concentration ratio was 10:1. Neutron irradiation giving a 5-Gy dose to precancerous tissue (corresponding to 21 Gy in tumor) resulted in an overall tumor response (OR) of 70% after a 4-wk posttreatment period. In contrast, the beam-only protocol gave an OR rate of only 28%. Once-repeated BNCT treatment with readministration of liposomes at an interval of 4, 6, or 8 wk resulted in OR rates of 70-88%, of which the complete response ranged from 37% to 52%. Because of the good therapeutic outcome, it was possible to extend the follow-up of BNCT treatment groups to 16 wk after the first treatment. No radiotoxicity to normal tissue was observed. A salient advantage of these liposomes was that only mild mucositis was observed in dose-limiting precancerous tissue with a sustained tumor response of 70-88%.

  4. Therapeutic efficacy of boron neutron capture therapy mediated by boron-rich liposomes for oral cancer in the hamster cheek pouch model

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    Heber, Elisa M. [Comision Nacional de Energia Atomica (CNEA), Buenos Aires (Argentina); Hawthorne, M. Frederick [Univ. of Missouri, Columbia, MO (United States). International Inst. of Nano and Molecular Medicine; Kueffer, Peter J. [Univ. of Missouri, Columbia, MO (United States). International Inst. of Nano and Molecular Medicine; Garabalino, Marcela A. [Comision Nacional de Energia Atomica (CNEA), Buenos Aires (Argentina); Thorp, Silvia I. [Comision Nacional de Energia Atomica (CNEA), Buenos Aires (Argentina); Pozzi, Emiliano C. C. [Comision Nacional de Energia Atomica (CNEA), Buenos Aires (Argentina); Hughes, Andrea Monti [Comision Nacional de Energia Atomica (CNEA), Buenos Aires (Argentina); Maitz, Charles A. [Univ. of Missouri, Columbia, MO (United States). International Inst. of Nano and Molecular Medicine; Jalisatgi, Satish S. [Univ. of Missouri, Columbia, MO (United States). International Inst. of Nano and Molecular Medicine; Nigg, David W. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Curotto, Paula [Comision Nacional de Energia Atomica (CNEA), Buenos Aires (Argentina); Trivillin, Verónica A. [Comision Nacional de Energia Atomica (CNEA), Buenos Aires (Argentina); Schwint, Amanda E. [Comision Nacional de Energia Atomica (CNEA), Buenos Aires (Argentina)

    2014-11-11

    Unilamellar liposomes formulated with an equimolar mixture of cholesterol and 1,2-distearoyl-sn-glycero-3-phosphocholine, incorporating K[nido-7-CH3(CH2)15-7,8-C2B9H11] in the lipid bilayer, and encapsulating Na3[1-(2’-B10-H9)-2-NH3B10H8] were prepared by probe sonication and investigated in vivo. Microwave assisted digestion followed by inductively coupled plasma-optical emission spectroscopy was utilized to determine the biodistribution of boron in various tissues following either a single tail vein injection or two identical injections (separated by 24 hours) of the liposomal suspension in BALB/c mice bearing EMT6 mammary adenocarcinomas in their right flank. Double-injection protocols resulted in a boron content in the tumor exceeding 50 µg of boron per gram of tissue for 48 to 72 hours subsequent to the initial injection while tumor:blood boron ratios were more ideal from 54 hours (1.9:1) to 96 hours (5.7:1) subsequent to the initial injection. Tumor bearing mice were given a double-injection of liposomes containing the 10B-enriched analogs of the aforementioned agents and subjected to a 30 minute irradiation by thermal neutrons with a flux of 8.8 x 108 (±7%) neutrons/cm2 s integrated over the energy range of 0.0 – 0.414 eV. Significant tumor response for a single BNCT treatment was demonstrated by growth curves versus a control group. Vastly diminished tumor growth was witnessed at 14 days (186% increase versus 1551% in controls) in mice that were given a second injection/radiation treatment 7 days after the first. Mice given a one hour neutron irradiation following the double-injection of liposomes had a similar response (169% increase at 14 days) suggesting that neutron fluence is the limiting factor towards BNCT efficacy in this study.

  5. Boron-Based Drug Design.

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    Ban, Hyun Seung; Nakamura, Hiroyuki

    2015-06-01

    The use of the element boron, which is not generally observed in a living body, possesses a high potential for the discovery of new biological activity in pharmaceutical drug design. In this account, we describe our recent developments in boron-based drug design, including boronic acid containing protein tyrosine kinase inhibitors, proteasome inhibitors, and tubulin polymerization inhibitors, and ortho-carborane-containing proteasome activators, hypoxia-inducible factor 1 inhibitors, and topoisomerase inhibitors. Furthermore, we applied a closo-dodecaborate as a water-soluble moiety as well as a boron-10 source for the design of boron carriers in boron neutron capture therapy, such as boronated porphyrins and boron lipids for a liposomal boron delivery system.

  6. Development of liposomal salbutamol sulfate dry powder inhaler formulation.

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    Huang, Wen-Hua; Yang, Zhi-Jun; Wu, Heng; Wong, Yuen-Fan; Zhao, Zhong-Zhen; Liu, Liang

    2010-01-01

    The purpose of our study was to develop a formulation of liposomal salbutamol sulfate (SBS) dry powder inhaler (DPI) for the treatment of asthma. Liposomes of high encapsulation efficiency (more than 80%) were prepared by a vesicular phospholipid gel (VPG) technique. SBS VPG liposomes were subjected to lyophilization using different kinds of cryoprotectants in various mass ratios. Coarse lactose (63-106 microm) in different mass ratios was used as a carrier. Magnesium stearate (0.5%) was added as a lubricator. The dry liposomal powders were then crushed by ball milling and sieved through a 400-mesh sieve to control the mean particle size at about 10 microm. The effects of different kinds of cryoprotectants and the amount of lactose carrier on the fine particle fraction (FPF) of SBS were investigated. The results showed that the developed formulation of liposomal dry powder inhaler was obtained using lactose as a cryoprotectant with a mass ratio of lyophilized powder to carrier lactose at 1 : 5; 0.5% magnesium stearate was used as a lubricator. The value of FPF for SBS was 41.51+/-2.22% for this formulation. Sustained release of SBS from the VPG liposomes was found in the in vitro release study. The study results offer the promising possibility of localized pulmonary liposomal SBS delivery in the anhydrous state.

  7. Liposomal cytarabine for leukemic and lymphomatous meningitis: recent developments.

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    Benesch, Martin; Urban, Christian

    2008-02-01

    Liposomal cytarabine (Depocyte) is a sustained-release formulation of cytarabine developed for intrathecal administration, ensuring prolonged cytotoxic drug concentrations of cytarabine in cerebrospinal fluid. Although liposomal cytarabine is increasingly used for the treatment (and prophylaxis) of CNS involvement in patients with leukemia/lymphoma, many of the recently presented clinical trials on liposomal cytarabine were retrospective in nature or used this drug on a compassionate basis. So far, one randomized Phase III study has shown significantly better response rates in patients with lymphomatous meningitis who received liposomal cytarabine compared with free cytarabine. Considerable concerns about the safety of this drug arose from recent observations that liposomal cytarabine might contribute to neurologic side effects when given too closely to high-dose systemic chemotherapy known to penetrate the brain-blood barrier. Superior efficacy of liposomal cytarabine compared with standard intrathecal therapy should be confirmed in prospective clinical trials. Careful adherence with preventive measures might help physicians to minimize side effects possibly related to the administration of liposomal cytarabine.

  8. [Development of ultrasonic cancer therapy using ultrasound sensitive liposome].

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    Suzuki, Ryo; Oda, Yusuke; Utoguchi, Naoki; Maruyama, Kazuo

    2010-12-01

    Ultrasound (US) has been utilized as a useful tool for diagnosis and therapy. US mediated drug and gene delivery is paid to attention as a non-invasive system. The combination of US and microbubbles generated microjet stream by inducing disruption of bubbles and resulted in enhancing permeability of cell membrane. This phenomenon has been utilized as driving force for drug and gene delivery. Recently, we developed ultrasound sensitive liposome [Bubble liposome (BL)] containing perfluoropropane gas. US combined with BL could effectively transfer gene in vivo compared to conventional cationic liposomes. Using this method, we succeeded to obtain a therapeutic effect in cancer gene therapy with Interleukin-12 corded plasmid DNA. Therefore, it is expected that US combined with BL might be a useful non-viral vector system. From this result, the fusion of liposomal and ultrasound technologies would be important for establishment of advanced cancer therapy.

  9. Theranostic liposomes for cancer diagnosis and treatment: current development and pre-clinical success.

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    Muthu, Madaswamy S; Feng, Si-Shen

    2013-02-01

    Liposomes are one of the effective drug delivery systems that are developed based on the nanotechnology concept. Liposomal formulation is the first nanomedicine approved by the US FDA for clinical application. Recently, the marketed liposomes and stealth liposomes have made impact for cancer therapy. In addition, a few receptor-targeted liposome products have been in different phases of clinical trials, which are yet to be marketed. In the present editorial, the advantages of vitamin E TPGS-coated liposomes over the currently available PEG-coated liposomes will be described and their great potentials for nanotheranostics for cancer imaging and therapy will be covered.

  10. Liposomal Drug Product Development and Quality: Current US Experience and Perspective.

    Science.gov (United States)

    Kapoor, Mamta; Lee, Sau L; Tyner, Katherine M

    2017-02-03

    Research in the area of liposomes has grown substantially in the past few decades. Liposomes are lipid bilayer structures that can incorporate drug substances to modify the drug's pharmacokinetic profile thereby improving drug delivery. The agency has received over 400 liposomal drug product submissions (excluding combination therapies), and there are currently eight approved liposomal drug products on the US market. In order to identify the pain points in development and manufacturing of liposomal drug products, a retrospective analysis was performed from a quality perspective on submissions for new and generic liposomal drug products. General analysis on liposomal drug product submissions was also performed. Results indicated that 96% of the submissions were Investigational New Drug (IND) applications, 3% were New Drug Applications (NDAs), and the remaining 1% was Abbreviated New Drug Applications (ANDAs). Doxorubicin hydrochloride was the most commonly used drug substance incorporated into the liposomes (31%). The majority of the liposomal products were administered via intravenous route (84%) with cancer (various types) being the most common indication (63%). From a quality perspective, major challenges during the development of liposomal drug products included identification and (appropriate) characterization of critical quality attributes of liposomal drug products and suitable control strategies during product development. By focusing on these areas, a faster and more efficient development of liposomal drug products may be achieved. Additionally, in this way, the drug review process for such products can be streamlined.

  11. Development of Liposomal Ciprofloxacin to Treat Lung Infections

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    David Cipolla

    2016-03-01

    Full Text Available Except for management of Pseudomonas aeruginosa (PA in cystic fibrosis, there are no approved inhaled antibiotic treatments for any other diseases or for infections from other pathogenic microorganisms such as tuberculosis, non-tuberculous mycobacteria, fungal infections or potential inhaled biowarfare agents including Francisella tularensis, Yersinia pestis and Coxiella burnetii (which cause pneumonic tularemia, plague and Q fever, respectively. Delivery of an antibiotic formulation via the inhalation route has the potential to provide high concentrations at the site of infection with reduced systemic exposure to limit side effects. A liposomal formulation may improve tolerability, increase compliance by reducing the dosing frequency, and enhance penetration of biofilms and treatment of intracellular infections. Two liposomal ciprofloxacin formulations (Lipoquin® and Pulmaquin® that are in development by Aradigm Corporation are described here.

  12. Boron

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    ... an eye wash. Boron was used as a food preservative between 1870 and 1920, and during World Wars ... chemical symbol), B (symbole chimique), Borate, Borate de Sodium, Borates, Bore, Boric Acid, Boric Anhydride, Boric Tartrate, ...

  13. Developments in boron magnetic resonance imaging (MRI)

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    Schweizer, M.

    1995-11-01

    This report summarizes progress during the past year on maturing Boron-11 magnetic resonance imaging (MRI) methodology for noninvasive determination of BNCT agents (BSH) spatially in time. Three major areas are excerpted: (1) Boron-11 MRI of BSH distributions in a canine intracranial tumor model and the first human glioblastoma patient, (2) whole body Boron-11 MRI of BSH pharmacokinetics in a rat flank tumor model, and (3) penetration of gadolinium salts through the BBB as a function of tumor growth in the canine brain.

  14. Development and characterization of an innovative heparin coating to stabilize and protect liposomes against adverse immune reactions.

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    Duehrkop, Claudia; Leneweit, Gero; Heyder, Christoph; Fromell, Karin; Edwards, Katarina; Ekdahl, Kristina N; Nilsson, Bo

    2016-05-01

    Liposomes have been recognized as excellent drug delivery systems, but when they come in direct contact with different blood components they may trigger an immediate activation of the innate immune system. The aim of the present study was to produce long-circulating, blood-compatible liposomes by developing a construct of liposomes covered by a novel unique heparin complex (CHC; 70 heparin molecules per complex) to avoid recognition by the innate immune system. Unilamellar, cationic liposomes were produced by hand extrusion through a 100-nm polycarbonate membrane. Coating of liposomes with the macromolecular CHC was accomplished by electrostatic interactions. Dynamic light scattering as well as QCM-D measurements were used to verify the electrostatic deposition of the negatively charged CHC to cationic liposomes. The CHC-coated liposomes did not aggregate when in contact with lepirudin anti-coagulated plasma. Unlike previous attempts to coat liposomes with heparin, this technique produced freely moveable heparin strands sticking out from the liposome surface, which exposed AT binding sites reflecting the anticoagulant potentials of the liposomes. In experiments using lepirudin-anticoagulated plasma, CHC-coated liposomes, in contrast to non-coated control liposomes, did not activate the complement system, as evidenced by low C3a and sC5b-9 generation and reduced leakage from the liposomes. In conclusion, we show that liposomes can be successfully coated with the biopolymer CHC, resulting in biocompatible and stable liposomes that have significant application potential.

  15. Development of monodispersed and functional magnetic polymeric liposomes via simple liposome method

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    Liang Xiaofei; Wang Hanjie [Tianjin University and Tianjin Key Laboratory of Composites and Functional Materials, Institute of Nanobiotechnology, School of Materials Science and Engineering (China); Jiang Xinguo [Fudan University, School of Pharmacy (China); Chang Jin, E-mail: jinchang@tju.edu.c [Tianjin University and Tianjin Key Laboratory of Composites and Functional Materials, Institute of Nanobiotechnology, School of Materials Science and Engineering (China)

    2010-06-15

    We are reporting a simple and rapid method to prepare superparamagnetic, controlled size, and monodispersed magnetic cationic polymeric liposomes (MCPL) by octadecyl quaternized carboxymethyl chitosan (OQCMC) and cholesterol. The whole process is only about 25 min with simple thin-film dispersion and solvent evaporation method. Hydrophilic magnetic nanoparticles (LM) and hydrophobic magnetic nanoparticles (BM) can be encapsulated into these cationic polymeric liposomes, simultaneously or respectively. A model hydrophobic drug indomethacin can be successfully filled in MCPL with high drug loading capacity 22%. MCPL encapsulating BM also showed strong DNA (pEGFP) binding ability. Drug-loaded MCPL have a long and controlled sustained release profile by changing the number of polymeric lipid layer. These functional MCPL nanospheres can be allowed to serve as ideal candidates for many biomedical applications.Graphical AbstractA simple and rapid liposome method was reported to prepare superparamagnetic, controlled size, and monodispersed magnetic cationic polymeric liposomes (MCPL) by polymeric surfactant, octadecyl quaternized carboxymethyl chitosan (OQCMC), and cholesterol. Hydrophilic Fe{sub 3}O{sub 4} ferrofluid and hydrophobic magnetic nanoparticles can be encapsulated into these cationic polymeric liposomes, simultaneously or respectively. Hydrophobic drug indomethacin can be encapsulated into this MCPL with high encapsulating efficiency and with controlled release profile by changing the number of polymeric lipid layer.

  16. FORMULATION AND DEVELOPMENT OF LIPOSOMAL GEL FOR TOPICAL DRUG DELIVERY SYSTEM

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    Suraj R. Wasankar*, Syed M. Faizi and Abhisek D. Deshmuk

    2012-11-01

    Full Text Available Aim: The aims of this study were to develop liposome enriched Dexibuprofen liposomal hydrogels for topical delivery, perform in vitro release studies and in vivo permeation studies through mice/rat skin, and evaluate the efficacy of liposomal gels against inflammation induced rats. The purpose was to provide the delivery of the topical drug at a sustained rate across intact skin to improve bioavailability and inflammation control for longer period from liposomal gels.Method: Phosphatidylcholine, Cholesterol and Dexibuprofen were dissolved in chloroform/methanol (2:1, v/v mixture and subsequently transferred into a pear-shaped flask connected to a Rotavapor (Büchi- type. Rotary evaporation method was used for the formulation of liposomes.Result: liposome prepared was evaluated for particle size measurement, percent drug entrapment, diffusion study, skin permeation study and in vivo study. F-7 batch found to be optimized batch having particle size 5.40 µm, % drug entrapment 61.70, % CDR 75.35 %. Hence F-7 batch further evaluated for skin permeation study, skin deposition study, in vivo study and stability study.Conclusion: The present study has been a satisfactory attempt to formulate and evaluate liposome of Dexibuprofen and liposomal gel with a providing sustained delivery of drug. From skin permeation study and in vivo study it was concluded that the prepared liposome of Dexibuprofen may prove to be potential candidate for safe and effective sustained drug delivery over an extended period of time which can reduce dosing frequency.

  17. Distribution of technetium-99m PEG-liposomes during oligofructose-induced laminitis development in horses

    NARCIS (Netherlands)

    Underwood, Claire; Pollitt, Christopher C.; Metselaar, Josbert M.; Laverman, Peter; van Bloois, Louis; van den Hoven, Jolanda M.; Storm, G; van Eps, Andrew W.

    2015-01-01

    Liposomes are phospholipid nanoparticles used for targeted drug delivery. This study aimed to determine whether intravenous liposomes accumulate in lamellar tissue during laminitis development in horses so as to assess their potential for targeted lamellar drug delivery. Polyethylene-glycol (PEG) co

  18. Development of paclitaxel-loaded liposomal nanocarrier stabilized by triglyceride incorporation

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    Hong SS

    2016-09-01

    Full Text Available Soon-Seok Hong,1 Ju Yeon Choi,2 Jong Oh Kim,2 Mi-Kyung Lee,3 So Hee Kim,4 Soo-Jeong Lim1 1Department of Bioscience and Bioengineering, Sejong University, Seoul, 2College of Pharmacy, Yeungnam University, Gyeongsan, 3College of Pharmacy, Woosuk University, Wanju-gun, Jeollabuk-do, 4College of Pharmacy and Research Institute of Pharmaceutical Science and Technology, Ajou University, Suwon, Republic of Korea Abstract: Studies have highlighted the challenge of developing injectable liposomes as a paclitaxel (PTX carrier, a challenge attributable to the limitations in liposomal stability caused by PTX loading. Poor stability of PTX-loaded liposomes is caused by PTX-triggered aggregation or fusion of liposomal membranes and is exacerbated in the presence of PEGylated lipid. In the present study, the effect of triglyceride incorporation on the stability of PTX-loaded/PEGylated liposomes was explored. Incorporation of a medium chain triglyceride Captex 300 into saturated phosphatidylcholine (PC-based liposomes (1,2-dimyristoyl-sn-glycero-3-phosphocholine [DMPC]:cholesterol [CHOL]:N-(Carbonyl-methoxypolyethyleneglycol 2000-1, 2-distearoyl-sn-glycero-3-phospho-ethanolamine [PE-PEG], produced a fine, homogeneous, and membrane-filterable PTX-loaded liposomes fulfilling the requirement of an injectable lipid formulation. Triglyceride incorporation also greatly inhibited the time-dependent leakage of PTX from saturated PC-based liposomes, which appears to be mediated by the inhibition of liposome fusion. In contrast, triglyceride incorporation induced the destabilization and PTX leakage of unsaturated PC-based liposomes, indicating the opposite effect of triglyceride depending on the fluidity status of PC constituting the liposomal membrane. PTX release profile and the in vitro and in vivo anticancer efficacy of triglyceride-incorporated DMPC:CHOL:PE-PEG liposomes were similar to Taxol® while the toxicity of liposomal PTX was significantly lower than that of

  19. Liposomes and nanotechnology in drug development: focus on oncotargets

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    Kozako T

    2012-09-01

    Full Text Available Tomohiro Kozako,1 Naomichi Arima,2 Makoto Yoshimitsu,3 Shin-Ichro Honda,1 Shinji Soeda11Department of Biochemistry, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan; 2Division of Hematology and Immunology, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan; 3Department of Hematology and Immunology, Kagoshima University Hospital, Kagoshima, JapanAbstract: Nanotechnology is the development of an engineered device at the atomic, molecular, and macromolecular level in the nanometer range. Advances in nanotechnology have proven beneficial in therapeutic fields such as drug-delivery and gene/protein delivery. Antigen delivery systems are important for inducing and modifying immune responses. In cellular immunity, cytotoxic T lymphocytes (CTLs are important in the host defense against tumors. Key to the development of CTL-inducible vaccines is the ability to deliver antigens to antigen-presenting cells efficiently and to induce the subsequent activation of T cell-mediated immunity without adjuvants, as they can induce excessive inflammation leading to systemic febrile disease. Since expression and cloning methods for tumor-associated antigens have been reported, cancer vaccines that induce effective cell immunity may be promising therapeutic candidates, but Th2 cells are undesirable for use in cancer immunotherapy. Peptide vaccines have immunological and economic advantages as cancer vaccines because CTL epitope peptides from tumor-associated antigens have high antigen-specificity. However, cancer vaccines have had limited effectiveness in clinical responses due to the ability of cancer cells to “escape” from cancer immunity and a low efficiency of antigen-specific CTL induction due to immunogenic-free synthetic peptides. In contrast, carbohydrate-decorated particles such as carbohydrate-coated liposomes with encapsulated antigens might be more suitable as

  20. Application of surface-linked liposomal antigens to the development of vaccines that induce both humoral and cellular immunity.

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    Uchida, Tetsuya; Taneichi, Maiko

    2014-01-01

    The first characteristic identified in surface-linked liposomal antigens was the ability to induce antigen-specific, IgE-selective unresponsiveness. These results remained consistent even when different coupling procedures were employed for antigens with liposomes or for liposomes with different lipid components. The potential usefulness of surface-linked liposomal antigens for application to vaccine development was further investigated. During this investigation, a significant difference was observed in the recognition of liposomal antigens by antigen-presenting cells between liposomes with different lipid components, and this difference correlated closely with the adjuvant activity of liposomes. In addition to this "quantitative" difference between liposomes with differential lipid components, a "qualitative" difference (i.e., a differential ability to induce cross-presentation) was observed between liposomes with different lipid components. Therefore, by utilizing the ability to induce cross-presentation, surface-linked liposomal antigens might be used to develop virus vaccines that would induce cytotoxic T lymphocyte (CTL) responses. We have successfully developed a liposome vaccine that is capable of inducing CTL responses against internal antigens of influenza viruses and thus removing virus-infected cells in the host. This CTL-based liposomal vaccine might be applicable to the development of vaccines against influenza and other viruses that frequently undergo changes in their surface antigenic molecules.

  1. DESIGN, DEVELOPMENT AND CHARACTERIZATION OF LIPOSOMAL NEEM GEL

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    ASMITA SINGH

    2014-04-01

    Full Text Available Purpose: Liposomal formulations have been successfully used in the treatment of a number of dermatological diseases. Various synthetic as well as herbal drugs are incorporated into liposome to improve its efficacy. Incorporation of herbal extract into liposome reduces side effects which are associated with the synthetic ones. Azadirachta indica leaves possesse good anti bacterial activity, confirming the great potential of bioactive compounds of neem. Among aqueous extract and alcoholic extract, alcoholic leaf extracts of A. indica were found to be more active towards the bacterial species. Hence, this extract was incorporated into liposomes to enhance its activity in skin delivery. The objective of the present research work is to convert this age old miraculous herb into nanotechnology based formulations i.e. liposomes. An attempt has been made to prepare liposomal Neem gel for topical use for anti-microbial activity. Methods: Methanolic Neem Extract (MeNE was incorporated into liposomes by thin film hydration method. The batch having lipid ratio i.e. Soya lecithin: Cholesterol (4:1; MeNE concentration 80 mg with entrapment efficiency 69.52 ±1.9% was finalized. Results and Conclusions: The vesicle size was found to be 3.2μm ± 0.67. In vitro drug diffusion and skin retention from liposomal gel was found to be 62.178% ± 0.91 and 20.03% ± 0.63 respectively. Stability studies indicated that formulation was stable over a period of 3 months when stored at 2-8°C.

  2. Development of a liposomal nanodelivery system for nevirapine

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    Krishnan Uma M

    2010-07-01

    Full Text Available Abstract Background The treatment of AIDS remains a serious challenge owing to high genetic variation of Human Immunodeficiency Virus type 1 (HIV-1. The use of different antiretroviral drugs (ARV is significantly limited by severe side-effects that further compromise the quality of life of the AIDS patient. In the present study, we have evaluated a liposome system for the delivery of nevirapine, a hydrophobic non-nucleoside reverse transcriptase inhibitor. Liposomes were prepared from egg phospholipids using thin film hydration. The parameters of the process were optimized to obtain spherical liposomes below 200 nm with a narrow polydispersity. The encapsulation efficiency of the liposomes was optimized at different ratios of egg phospholipid to cholesterol as well as drug to total lipid. The data demonstrate that encapsulation efficiency of 78.14% and 76.25% were obtained at egg phospholipid to cholesterol ratio of 9:1 and drug to lipid ratio of 1:5, respectively. We further observed that the size of the liposomes and the encapsulation efficiency of the drug increased concomitantly with the increasing ratio of drug and lipid and that maximum stability was observed at the physiological pH. Thermal analysis of the drug encapsulated liposomes indicated the formation of a homogenous drug-lipid system. The magnitude of drug release from the liposomes was examined under different experimental conditions including in phosphate buffered saline (PBS, Dulbecco's Modified Eagle's Medium (DMEM supplemented with 10% fetal bovine serum or in the presence of an external stimulus such as low frequency ultrasound. Within the first 20 minutes 40, 60 and 100% of the drug was released when placed in PBS, DMEM or when ultrasound was applied, respectively. We propose that nevirapine-loaded liposomal formulations reported here could improve targeted delivery of the anti-retroviral drugs to select compartments and cells and alleviate systemic toxic side effects as a

  3. Development and Characterization of Liposomal Doxorubicin Hydrochloride with Palm Oil

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    Bahareh Sabeti

    2014-01-01

    Full Text Available The usage of natural products in pharmaceuticals has steadily seen improvements over the last decade, and this study focuses on the utilization of palm oil in formulating liposomal doxorubicin (Dox. The liposomal form of Dox generally minimizes toxicity and enhances target delivery actions. Taking into account the antiproliferative and antioxidant properties of palm oil, the aim of this study is to design and characterize a new liposomal Dox by replacing phosphatidylcholine with 5% and 10% palm oil content. Liposomes were formed using the freeze_thaw method, and Dox was loaded through pH gradient technique and characterized through in vitro and ex vivo terms. Based on TEM images, large lamellar vesicles (LUV were formed, with sizes of 438 and 453 nm, having polydispersity index of 0.21 ± 0.8 and 0.22 ± 1.3 and zeta potentials of about −31 and −32 mV, respectively. In both formulations, the entrapment efficiency was about 99%, and whole Dox was released through 96 hours in PBS (pH = 7.4 at 37°C. Comparing cytotoxicity and cellular uptake of LUV with CaelyxR on MCF7 and MDA-MBA 231 breast cancer cell lines indicated suitable uptake and lower IC50 of the prepared liposomes.

  4. Development and characterization of liposomal doxorubicin hydrochloride with palm oil.

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    Sabeti, Bahareh; Noordin, Mohamed Ibrahim; Mohd, Shaharuddin; Hashim, Rosnani; Dahlan, Afendi; Javar, Hamid Akbari

    2014-01-01

    The usage of natural products in pharmaceuticals has steadily seen improvements over the last decade, and this study focuses on the utilization of palm oil in formulating liposomal doxorubicin (Dox). The liposomal form of Dox generally minimizes toxicity and enhances target delivery actions. Taking into account the antiproliferative and antioxidant properties of palm oil, the aim of this study is to design and characterize a new liposomal Dox by replacing phosphatidylcholine with 5% and 10% palm oil content. Liposomes were formed using the freeze_thaw method, and Dox was loaded through pH gradient technique and characterized through in vitro and ex vivo terms. Based on TEM images, large lamellar vesicles (LUV) were formed, with sizes of 438 and 453 nm, having polydispersity index of 0.21 ± 0.8 and 0.22 ± 1.3 and zeta potentials of about -31 and -32 mV, respectively. In both formulations, the entrapment efficiency was about 99%, and whole Dox was released through 96 hours in PBS (pH = 7.4) at 37°C. Comparing cytotoxicity and cellular uptake of LUV with Caelyx(R) on MCF7 and MDA-MBA 231 breast cancer cell lines indicated suitable uptake and lower IC50 of the prepared liposomes.

  5. CELECOXIB LOADED LIPOSOMES: DEVELOPMENT, CHARACTERIZATION AND IN VITRO EVALUATION

    Directory of Open Access Journals (Sweden)

    M. Yasmin Begum

    2012-01-01

    Full Text Available CLX (celecoxib is a highly hydrophobic non-steroidal anti-inflammatory drug with high plasma protein binding. We describe here the encapsulation of CLX in MLVs composed of SPC and variable amounts of cholesterol. The influence of drug – lipid ratio was studied and amount of the drug could be encapsulated was optimized. The effect of cholesterol and other process parameters were studied to obtain the liposomal vesicles with desired quality. All the prepared formulations were characterized for their physico chemical properties such as appearance, vesicle size, vesicle size distribution and percentage drug entrapment. Stability of the liposomes in terms of their drug leakage and drug retention behaviour was studied by storing the liposomal formulations under different conditions for the period of 30 days. The optimized formulation parameters and process parameters resulted the liposomes with mean vesicle diameter of 4.81μ. The maximum percentage drug entrapment was achieved with the formulation CL3 which contains the drug – lipid ratio of 1:10%W/W and the percentage drug entrapment is equal to 72.33±0.64 (%. In vitro release data showed that release profile follows zero order kinetics. Celecoxib liposomes with good stability and appreciable controlled drug release with good retention of the drug even after 24 hours were prepared successfully.

  6. Development, characterization and in vivo evaluation of benzocaine-loaded liposomes.

    Science.gov (United States)

    Mura, Paola; Maestrelli, Francesca; González-Rodríguez, Maria Luisa; Michelacci, Ilaria; Ghelardini, Carla; Rabasco, Antonio M

    2007-08-01

    This study reports the development and in vivo evaluation of a liposomal formulation of the local anaesthetic benzocaine. Multi-lamellar (MLV) and small uni-lamellar (SUV) vesicles entrapping benzocaine were prepared using 50:50 w/w phosphatidylcholine-cholesterol as lipophilic phase and 50:50 v/v ethanol-water as hydrophilic phase. Liposome size, Zeta-potential, encapsulation efficiency and skin penetration properties were determined. Drug permeation from liposomal dispersions, as such or formulated in Carbopol gel, was evaluated through artificial lipophilic membranes and excised abdominal rat skin, whereas in vivo anaesthetic effect was tested on rabbits. Interestingly, addition of the drug into the hydrophilic phase, rather than into the lipophilic one, during liposome preparation enabled an improvement of the MLV's entrapment efficiency from 29.7% to 82.3%. On the other hand, sonication conditions to obtain SUV influenced size and polydispersity index of the vesicles and reduced the entrapment efficiency by about 30%. All liposomal-benzocaine formulations showed sustained release properties and a more intense anaesthetic effect than plain drug. Permeation experiments from drug solutions in gel containing the same amount of ethanol as in the liposomal formulations made it possible to exclude a possible enhancer effect of this solvent, at least when not used in liposomal formulations. MLV with the drug added into the hydrophilic phase gave the most effective formulation, showing a permeability coefficient value 2.5 times higher than that of the plain drug and allowing a significant improvement (Pbenzocaine. These results suggest that a suitably developed liposomal formulation of benzocaine can be of actual value for improving its clinical effectiveness in topical anaesthesia.

  7. Development of mannosylated liposomes for bioadhesive oral drug delivery via M cells of Peyer's patches.

    Science.gov (United States)

    Pukanud, Pongthep; Peungvicha, Penchom; Sarisuta, Narong

    2009-07-01

    The aim of this study was to develop mannosylated liposomes as bioadhesive carriers for oral drug delivery. Two kinds of acyclovir (ACV)-entrapped mannosylated liposomes, i.e. ManN-ACV-lip and PAM-ACV-lip, were prepared by the use of mannosamine HCl (ManN) and p-aminophenyl-alpha-D-mannopyranoside (PAM), respectively. The mean sizes, drug entrapment efficiency, and loading capacity values of all liposomal formulations were in the ranges of 233-371 nm, 82-95%, and 42-47%, respectively. The mean size of PAM-ACV-lip was significantly smaller than those of conventional ACV liposomes and ManN-ACV-lip due to the more conical packing parameter of mannose-conjugated phospholipid. The mannosylating group grafted into bilayer membrane resulted in a decrease in drug entrapment, owing to competitive binding. The in vitro drug absorptions through everted sacs of mice ileum of both mannosylated ACV liposomes were significantly higher than those of conventional ACV liposomes or suspension.

  8. Synthesis and evaluation of a novel liposome containing BPA-peptide conjugate for BNCT

    Energy Technology Data Exchange (ETDEWEB)

    Shirakawa, Makoto [Department of Graduate School of Comprehensive Human Sciences, Faculty of Functional and Regulatory Medical Sciences, University of Tsukuba (Japan)], E-mail: m0720347@md.tsukuba.ac.jp; Yamamto, Tetsuya; Nakai, Kei [Department of Graduate School of Comprehensive Human Sciences, Faculty of Functional and Regulatory Medical Sciences, University of Tsukuba (Japan); Aburai, Kenichi [Department of Pure and Applied Chemistry, Faculty of Science and Technology, Tokyo University of Science (Japan); Kawatobi, Sho [Faculty of Pharmaceutical Sciences, Toho University (Japan); Tsurubuchi, Takao; Yamamoto, Yohei [Department of Graduate School of Comprehensive Human Sciences, Faculty of Functional and Regulatory Medical Sciences, University of Tsukuba (Japan); Yokoyama, Yuusaku; Okuno, Hiroaki [Faculty of Pharmaceutical Sciences, Toho University (Japan); Matsumura, Akira [Department of Graduate School of Comprehensive Human Sciences, Faculty of Functional and Regulatory Medical Sciences, University of Tsukuba (Japan)

    2009-07-15

    We aimed at securing sufficient concentrations of {sup 10}B in boron neutron capture therapy (BNCT) by developing a new drug delivery system. We have designed and developed a novel lipid analog and succeeded in using it to develop the new boron component liposome. It consisted of three different kinds of amino acid derivatives and two fatty acids, and could react directly with the peptide synthesized first on resin by Fmoc solid-phase synthesis. In this study, lipid analog conjugated with HIV-TAT peptide (domain of human immunodeficiency virus TAT protein) and boronophenylalanine (BPA) was synthesized and successfully incorporated into liposomes.

  9. Metallomics in drug development: characterization of a liposomal cisplatin drug formulation in human plasma by CE-ICP-MS.

    Science.gov (United States)

    Nguyen, Tam T T N; Østergaard, Jesper; Stürup, Stefan; Gammelgaard, Bente

    2013-02-01

    A capillary electrophoresis inductively coupled plasma mass spectrometry method for separation of free cisplatin from liposome-encapsulated cisplatin and protein-bound cisplatin was developed. A liposomal formulation of cisplatin based on PEGylated liposomes was used as model drug formulation. The effect of human plasma matrix on the analysis of liposome-encapsulated cisplatin and intact cisplatin was studied. The presence of 1 % of dextran and 4 mM of sodium dodecyl sulfate in HEPES buffer was demonstrated to be effective in improving the separation of liposomes and cisplatin bound to proteins in plasma. A detection limit of 41 ng/mL of platinum and a precision of 2.1 % (for 10 μg/mL of cisplatin standard) were obtained. Simultaneous measurements of phosphorous and platinum allows the simultaneous monitoring of the liposomes, liposome-encapsulated cisplatin, free cisplatin and cisplatin bound to plasma constituents in plasma samples. It was demonstrated that this approach is suitable for studies of the stability of liposome formulations as leakage of active drug from the liposomes and subsequent binding to biomolecules in plasma can be monitored. This methodology has not been reported before and will improve characterization of liposomal drugs during drug development and in studies on kinetics.

  10. Preclinical development of a C6-ceramide NanoLiposome, a novel sphingolipid therapeutic.

    Science.gov (United States)

    Kester, Mark; Bassler, Jocelyn; Fox, Todd E; Carter, Carly J; Davidson, Jeff A; Parette, Mylisa R

    2015-06-01

    Despite the therapeutic potential of sphingolipids, the ability to develop this class of compounds as active pharmaceutical ingredients has been hampered by issues of solubility and delivery. Beyond these technical hurdles, significant challenges in completing the necessary preclinical studies to support regulatory review are necessary for commercialization. This review seeks to identify the obstacles and potential solutions in the translation of a novel liposomal technology from the academic bench to investigational new drug (IND) stage by discussing the preclinical development of the Ceramide NanoLiposome (CNL), which is currently being developed as an anticancer drug for the initial indication of hepatocellular carcinoma (HCC).

  11. Development of a liposome formulation for improved biodistribution and tumor accumulation of pentamidine for oncology applications.

    Science.gov (United States)

    Mérian, Juliette; De Souza, Raquel; Dou, Yannan; Ekdawi, Sandra N; Ravenelle, François; Allen, Christine

    2015-07-05

    Pentamidine isethionate, widely used for the treatment of parasitic infections, has shown strong anticancer activity in cancer cells and models of melanoma and lung cancer. Systemic administration of pentamidine is associated with serious toxicities, particularly renal, affecting as many as 95% of patients (O'Brien et al., 1997). This work presents the development of a liposome pentamidine formulation for greater tumor accumulation and lower drug exposure to vulnerable tissues. Liposomes formulated with saturated/unsaturated phospholipids of different chain lengths, varying cholesterol content, and surface PEG were explored to understand the effects of such variations on drug release, encapsulation efficiency, stability and in vivo performance. Saturated phospholipids with longer chain lengths, higher cholesterol content and PEG resulted in greater stability. The optimal formulation obtained showed significantly lower clearance rate (3.6 ± 1.2 mL/h/Kg) and higher AUC0-inf (348 ± 31 μmol/L × h) in vivo when compared to free drug (414 ± 138 mL/h/Kg and 2.58 ± 0.74 μmol/L × h, respectively). In tumor-bearing mice, liposomal delivery decreased kidney drug levels by up to 5-fold at 6 and 24h post-administration. Tumor drug exposure was up to 12.7-fold greater with liposomal administration compared to free drug. Overall, the liposomal pentamidine formulation developed has significant potential for the treatment of solid tumors.

  12. Development of Liposome containing sodium deoxycholate to enhance oral bioavailability of itraconazole

    Directory of Open Access Journals (Sweden)

    Zhenbao Li

    2017-03-01

    Full Text Available The aim of this study was to enhance oral bioavailability of itraconazole (ITZ by developing Liposome containing sodium deoxycholate (ITZ-Lip-NaDC. The liposome, consisting of egg yolk lecithin and sodium deoxycholate, was prepared by thin-film dispersion method. Differential Scanning Calorimetry (DSC results indicated an amorphous state in the liposome. The physicochemical characteristics including particle size, morphology, entrapment efficiency, dissolution properties were also investigated. The performance of single-pass intestinal infusion exhibited that the transport order of intestinal segment was jejunum, duodenum, colon and ileum, and that all the segments participated in the absorption of ITZ in intestinal tract. The bioavailability study in rats showed that the AUC0-72 of the liposome was nearly 1.67-fold higher than that of commercial capsules (SPORANOX in terms of oral administration, and the RSD of AUC0-72 of ITZ-Lip-NaDC was also decreased. Our results indicated that ITZ-Lip-NaDC liposome was facilitated to improve dissolution efficiency, augment transmembrane absorption, and then enhance the oral bioavailability of ITZ, successfully.

  13. Development of a cell-based bioassay for phospholipase A2-triggered liposomal drug release

    DEFF Research Database (Denmark)

    Arouri, Ahmad; Trojnar, Jakub; Schmidt, Steffen

    2015-01-01

    models, the pattern of sPLA2-assisted drug release is unknown due to the lack of a suitable bio-relevant model. We report here on the development of a novel bioluminescence living-cell-based luciferase assay for the monitoring of sPLA2-triggered release of luciferin from liposomes. To this end, we...

  14. Liposomes as nanomedical devices.

    Science.gov (United States)

    Bozzuto, Giuseppina; Molinari, Agnese

    2015-01-01

    Since their discovery in the 1960s, liposomes have been studied in depth, and they continue to constitute a field of intense research. Liposomes are valued for their biological and technological advantages, and are considered to be the most successful drug-carrier system known to date. Notable progress has been made, and several biomedical applications of liposomes are either in clinical trials, are about to be put on the market, or have already been approved for public use. In this review, we briefly analyze how the efficacy of liposomes depends on the nature of their components and their size, surface charge, and lipidic organization. Moreover, we discuss the influence of the physicochemical properties of liposomes on their interaction with cells, half-life, ability to enter tissues, and final fate in vivo. Finally, we describe some strategies developed to overcome limitations of the "first-generation" liposomes, and liposome-based drugs on the market and in clinical trials.

  15. Development of a cell-based bioassay for phospholipase A2-triggered liposomal drug release.

    Science.gov (United States)

    Arouri, Ahmad; Trojnar, Jakub; Schmidt, Steffen; Hansen, Anders H; Mollenhauer, Jan; Mouritsen, Ole G

    2015-01-01

    The feasibility of exploiting secretory phospholipase A2 (sPLA2) enzymes, which are overexpressed in tumors, to activate drug release from liposomes precisely at the tumor site has been demonstrated before. Although the efficacy of the developed formulations was evaluated using in vitro and in vivo models, the pattern of sPLA2-assisted drug release is unknown due to the lack of a suitable bio-relevant model. We report here on the development of a novel bioluminescence living-cell-based luciferase assay for the monitoring of sPLA2-triggered release of luciferin from liposomes. To this end, we engineered breast cancer cells to produce both luciferase and sPLA2 enzymes, where the latter is secreted to the extracellular medium. We report on setting up a robust and reproducible bioassay for testing sPLA2-sensitive, luciferin remote-loaded liposomal formulations, using 1,2-distearoyl-sn-glycero-3-phosphatidylcholine/1,2-distearoyl-sn-glycero-3-phosphatidylglycerol (DSPC/DSPG) 7:3 and DSPC/DSPG/cholesterol 4:3:3 as initial test systems. Upon their addition to the cells, the liposomes were degraded almost instantaneously by sPLA2 releasing the encapsulated luciferin, which provided readout from the luciferase-expressing cells. Cholesterol enhanced the integrity of the formulation without affecting its susceptibility to sPLA2. PEGylation of the liposomes only moderately broadened the release profile of luciferin. The provided bioassay represents a useful tool for monitoring active drug release in situ in real time as well as for testing and optimizing of sPLA2-sensitive lipid formulations. In addition, the bioassay will pave the way for future in-depth in vitro and in vivo studies.

  16. DEVELOPMENT AND CHARACTARIZATION OF PERINDOPRIL ERBUMINE LOADED ETHANOLIC LIPOSOMES

    Directory of Open Access Journals (Sweden)

    Prakash Goudanavar

    2014-03-01

    Full Text Available The present work describes the preparation of Perindopril erbumine ethosomes and study of effect of alcohol and phospholipid on transdermal delivery. Perindopril erbumine is an ACE inhibitor which slowly inhibits the activity of the enzyme ACE, which decreases the production of angiotensin II, is being involved in the blood pressure regulation. Perindopril erbumine loaded ethanolic Liposomes were prepared by an hot - cold method using different concentrations of Alcohol and Soya lecithin in different ratios and propylene glycol. The prepared ethosomal formulations were subjected to Vesicle size analysis, Morphological studies, Entrapment efficiency, In vitro release, Stability studies, In vitro permeation study and kinetic data analysis. The vesicle size of ethosomes varied between 1.96±0.003 to 4.56±0.008 µm (Without sonication and from 1.62±1.31 to 1.99±1.02 µm (With sonication, Entrapment efficiency between 43.91±0.57 to 78.04±0.30%. FT-IR, DSC and Zetapotential studies revealed the integrity of the drug in the formulations. In vitro release profiles indicated that the highest % of drug release is 95.22±0.35 over period of 24 hrs with 30% alcohol & 2% phospholipid (ETH8 compared to other formulations. The in vitro permeation across rat abdominal skin for the optimized formulations ETH3 and ETH8 after 24 hrs was found to be 79.63% and 85.33% respectively. Stability studies indicated that, the prepared ethosomes remained stable at refrigeration (4-8˚C and room (25±2˚C temperature. The prepared ethosomes showed promising results under in vitro conditions.

  17. The boron efflux transporter ROTTEN EAR is required for maize inflorescence development and fertility.

    Science.gov (United States)

    Chatterjee, Mithu; Tabi, Zara; Galli, Mary; Malcomber, Simon; Buck, Amy; Muszynski, Michael; Gallavotti, Andrea

    2014-07-01

    Although boron has a relatively low natural abundance, it is an essential plant micronutrient. Boron deficiencies cause major crop losses in several areas of the world, affecting reproduction and yield in diverse plant species. Despite the importance of boron in crop productivity, surprisingly little is known about its effects on developing reproductive organs. We isolated a maize (Zea mays) mutant, called rotten ear (rte), that shows distinct defects in vegetative and reproductive development, eventually causing widespread sterility in its inflorescences, the tassel and the ear. Positional cloning revealed that rte encodes a membrane-localized boron efflux transporter, co-orthologous to the Arabidopsis thaliana BOR1 protein. Depending on the availability of boron in the soil, rte plants show a wide range of phenotypic defects that can be fully rescued by supplementing the soil with exogenous boric acid, indicating that rte is crucial for boron transport into aerial tissues. rte is expressed in cells surrounding the xylem in both vegetative and reproductive tissues and is required for meristem activity and organ development. We show that low boron supply to the inflorescences results in widespread defects in cell and cell wall integrity, highlighting the structural importance of boron in the formation of fully fertile reproductive organs.

  18. Studies on preparation of folate-targeted boron liposomes as potential delivery agents for neutron capture therapy%叶酸靶向含硼脂质体的制备及其包封率的测定

    Institute of Scientific and Technical Information of China (English)

    王志会; 钱林学; 刘冬

    2012-01-01

    To prepare folate-targeted liposomes with high encapsulation efficiency is an effective targeted drug delivery agent for boron neutron capture therapy (BNCT). The double emulsion method is used to prepare liposomes. The combination of thin film hydration and ultrasonic dispersion method is used to prepare liposomes loaded with HBA,TBA or BBA. The content and the encapsulation efficiency of HBA,TBA or BBA liposomes are evaluated by high performance liquid chromatography ( HPLC). As the basis of the encapsulation efficiency, the optimal conditions for preparing liposomes were explored by the single factor method. The optimal chromatographic conditions of the three drugs were filtered out. They had a good linear relation in a range of 1 ~ 100 μg/mL. The encapsulation efficiency of HBA, TBA and BBA liposomes were 25. 7 % , 38. 9 % and 94. 8 % at the optimal preparation and condition. The optimal conditions for preparing BBA liposomes are as follows; the mass ratio of cholesterol and phospholipid is 1: 1, the ratio of drug and lipid is 1: 50 and the optimal pH value is 7. 4. The entrapment efficiency for BBA liposomes in the optimal groups reached 94. 8 % . The technique of preparing folate-tar-geted liposomes is feasible and the method of quality control is simple and high accuracy. The liposomes appeare to be round, and well separated with high entrapment efficiency.%制备具有良好靶向性及包封率高的硼脂质体,为硼中子俘获治疗方法的研究与应用建立了一个有效的靶向给药途径.采用复乳法及薄膜—超声分散法制备叶酸靶向硼脂质体,利用高效液相色谱法检测4—羟基苯硼酸4—Hydroxyphenylboronicacid (HBA)脂质体、2—噻吩硼酸2—thiophenylboric acid(TBA)脂质体、4—叔丁基苯硼酸4—tert-Butylphenylboronic Acid(BBA)脂质体的含量及包封率,以包封率为评价指标,采用单因素法优化脂质体的制备处方和工艺条件.筛选出HBA、TBA、BBA最优的色谱条件,分

  19. Redispersible liposomal-N-acetylcysteine powder for pulmonary administration: development, in vitro characterization and antioxidant activity.

    Science.gov (United States)

    Ourique, Aline Ferreira; Chaves, Paula Dos Santos; Souto, Gabriele Dadalt; Pohlmann, Adriana Raffin; Guterres, Silvia Stanisçuaski; Beck, Ruy Carlos Ruver

    2014-12-18

    Liposomal dry powders of N-acetylcysteine (SD-NAC-Lip) were developed for pulmonary administration. Liposomes were prepared by reverse phase evaporation and spray dried using lactose (10%, w/w) as drying adjuvant. The powders were characterized according to process yield, drug content, residual water content, particle size distribution, morphology and redispersion behavior. In vitro aerosol performance was evaluated using an eight-stage Andersen Cascade Impactor. Moreover, in vitro antioxidant activity was determined by measuring thiobarbituric acid reactive species (TBARS) present in the lungs of healthy Wistar rats after induction of oxidation by iron/EDTA. The spray-drying process had a high yield (71%±2), drug content (mg/g) according to the expected value, moisture content below 9%, geometric mean diameter under 3μm with span value lower than 1. Spherical particles were observed by scanning electron microscopy. Liposomal dry-powders were able to recover the nanometric size of the original dispersion after their redispersion in aqueous medium, as shown by laser diffraction and transmission electron microscopy. Furthermore, the powders presented aerodynamic diameter of about 7μm and respirable fraction above 30%, indicating suitable properties for pulmonary use. The encapsulation of N-acetylcysteine in liposomes was essential to maintain its in vitro antioxidant activity after the drying process. In addition, the powder containing the encapsulated drug had better in vitro antioxidant activity than the liquid and solid formulations containing the non-encapsulated drug, which makes it a good candidate for the treatment of pulmonary diseases associated with oxidative stress.

  20. Development and characterization of oral liposomes of vegetal ceramide based amphotericin B having enhanced dry solubility and solubility.

    Science.gov (United States)

    Skiba-Lahiani, Malika; Hallouard, François; Mehenni, Lyes; Fessi, Hatem; Skiba, Mohamed

    2015-03-01

    Despite the development of new antifungal, amphotericin B remains one of the most effective agents in the treatment of systemic fungal infections. Many patients exhibit nevertheless intolerance to amphotericin B at higher dosages and parenteral formulations present unlike per os ones, associated risks and high care cost. Free amphotericin B per os showed however an apparently poor absorption. In this study, we evaluate the potential of amphotericin B liposomes formulated with vegetal ceramides for oral administration. Ceramides, one of the constituents of cellular cytoplasmic membranes, constitute an important element in the construction and stability of their lipid bilayer. To fulfill this objective, vegetal ceramides, composed essentially of glucosylceramides, were firstly incorporated in various liposome preparations, entrapping or not amphotericin B, in comparison with phosphatidylcholine liposomes. Then, these preparations were introduced in an "Artificial-Stomach-Duodenum" model to improve their stability for oral administration. The formulation of amphotericin B liposomes containing ceramides presented a mean hydrodynamic size of about 200nm. We showed also that cholesterol and phospholipids are required to prevent drug leakage and to obtain lamellar structure respectively. In "Artificial-Stomach-Duodenum" model, ceramides conferred to liposomes better membrane stability. In addition, ceramides did not alter their drug encapsulation yield being by 75%. This could be explained by the fact that ceramides as we proved, limited the detergent effect of bile salts on liposome membranes.

  1. Liposomal chemotherapeutics.

    Science.gov (United States)

    Gentile, Emanuela; Cilurzo, Felisa; Di Marzio, Luisa; Carafa, Maria; Ventura, Cinzia Anna; Wolfram, Joy; Paolino, Donatella; Celia, Christian

    2013-12-01

    Currently, six liposomal chemotherapeutics have received clinical approval and many more are in clinical trials or undergoing preclinical evaluation. Liposomes exhibit low toxicity and improve the biopharmaceutical features and therapeutic index of drugs, thereby increasing efficacy and reducing side effects. In this review we discuss the advantages of using liposomes for the delivery of chemotherapeutics. Gemcitabine and paclitaxel have been chosen as examples to illustrate how the performance of a metabolically unstable or poorly water-soluble drug can be greatly improved by liposomal incorporation. We look at the beneficial effects of liposomes in a variety of solid and blood-borne tumors, including thyroid cancer, pancreatic cancer, breast cancer and multiple myeloma.

  2. 78 FR 16692 - Prospective Grant of Start-Up Option Exclusive License: The Development of Liposomal Therapeutic...

    Science.gov (United States)

    2013-03-18

    ... Development of Liposomal Therapeutic Agents for the Treatment of Human Epithelial Cancers and Liposarcomas...: ovary, pancreas, metastatic skin, head and neck, colon, kidney, non-small cell lung, or liposarcoma.... Richard U. Rodriguez, Director, Division of Technology Development & Transfer, Office of...

  3. Carborane derivative development for boron neutron capture therapy. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Barnum, Beverly A.; Yan Hao; Moore, Roger; Hawthorne, M. Frederick; Baum, Kurt

    1999-04-01

    Boron Neutron Capture Therapy [BNCT] is a binary method of cancer therapy based on the capture of neutrons by a boron-10 atom [{sup 10}B]. Cytotoxic {sup 7}Li nuclei and {alpha}-particles are emitted, with a range in tissue of 9 and 5 {micro}m, respectively, about one cell diameter. The major obstacle to clinically viable BNCT is the selective localization of 5-30 ppm {sup 10}B in tumor cells required for effective therapy. A promising approach to BNCT is based on hydrophilic boron-rich oligomeric phosphate diesters, or ''trailers'' that have been shown to concentrate selectively in tumor tissue. Examples of these compounds were prepared previously at high cost using an automated DNA synthesizer. Direct synthesis methods are needed for the production of gram-scale quantities for further biological evaluation. The work accomplished as a result of the collaboration between Fluorochem, Inc. and UCLA demonstrates that short oligomers containing at least five carborane units with four phosphodiester linkages can be prepared in substantial quantities. This work was accomplished by the application of standard phosphoramidite coupling chemistry.

  4. tassel-less1 encodes a boron channel protein required for inflorescence development in maize.

    Science.gov (United States)

    Leonard, April; Holloway, Beth; Guo, Mei; Rupe, Mary; Yu, GongXin; Beatty, Mary; Zastrow-Hayes, Gina; Meeley, Robert; Llaca, Victor; Butler, Karlene; Stefani, Tony; Jaqueth, Jennifer; Li, Bailin

    2014-06-01

    tassel-less1 (tls1) is a classical maize (Zea mays) inflorescence mutant. Homozygous mutant plants have no tassels or very small tassels, and ear development is also impaired. Using a positional cloning approach, ZmNIP3;1 (a NOD26-like intrinsic protein) was identified as the candidate gene for tls1. The ZmNIP3;1 gene is completely deleted in the tls1 mutant genome. Two Mutator-insertional TUSC alleles of ZmNIP3;1 exhibited tls1-like phenotypes, and allelism tests confirmed that the tls1 gene encodes ZmNIP3;1. Transgenic plants with an RNA interference (RNAi) construct to down-regulate ZmNIP3;1 also showed tls1-like phenotypes, further demonstrating that TLS1 is ZmNIP3;1. Sequence analysis suggests that ZmNIP3;1 is a boron channel protein. Foliar application of boron could rescue the tls1 phenotypes and restore the normal tassel and ear development. Gene expression analysis indicated that in comparison with that of the wild type or tls1 plants treated with boron, the transition from the vegetative to reproductive phase or the development of the floral meristem is impaired in the shoot apical meristem of the tls1 mutant plants. It is concluded that the tls1 mutant phenotypes are caused by impaired boron transport, and boron is essential for inflorescence development in maize.

  5. Co-loaded paclitaxel/rapamycin liposomes: Development, characterization and in vitro and in vivo evaluation for breast cancer therapy.

    Science.gov (United States)

    Eloy, Josimar O; Petrilli, Raquel; Topan, José Fernando; Antonio, Heriton Marcelo Ribeiro; Barcellos, Juliana Palma Abriata; Chesca, Deise L; Serafini, Luciano Neder; Tiezzi, Daniel G; Lee, Robert J; Marchetti, Juliana Maldonado

    2016-05-01

    Paclitaxel and rapamycin have been reported to act synergistically to treat breast cancer. Albeit paclitaxel is available for breast cancer treatment, the most commonly used formulation in the clinic presents side effects, limiting its use. Furthermore, both drugs present pharmacokinetics drawbacks limiting their in vivo efficacy and clinic combination. As an alternative, drug delivery systems, particularly liposomes, emerge as an option for drug combination, able to simultaneously deliver co-loaded drugs with improved therapeutic index. Therefore, the purpose of this study is to develop and characterize a co-loaded paclitaxel and rapamycin liposome and evaluate it for breast cancer efficacy both in vitro and in vivo. Results showed that a SPC/Chol/DSPE-PEG (2000) liposome was able to co-encapsulate paclitaxel and rapamycin with suitable encapsulation efficiency values, nanometric particle size, low polydispersity and neutral zeta potential. Taken together, FTIR and thermal analysis evidenced drug conversion to the more bioavailable molecular and amorphous forms, respectively, for paclitaxel and rapamycin. The pegylated liposome exhibited excellent colloidal stability and was able to retain drugs encapsulated, which were released in a slow and sustained fashion. Liposomes were more cytotoxic to 4T1 breast cancer cell line than the free drugs and drugs acted synergistically, particularly when co-loaded. Finally, in vivo therapeutic evaluation carried out in 4T1-tumor-bearing mice confirmed the in vitro results. The co-loaded paclitaxel/rapamycin pegylated liposome better controlled tumor growth compared to the solution. Therefore, we expect that the formulation developed herein might be a contribution for future studies focusing on the clinical combination of paclitaxel and rapamycin.

  6. Co-loaded paclitaxel/rapamycin liposomes: Development, characterization and in vitro and in vivo evaluation for breast cancer therapy

    Science.gov (United States)

    Eloy, Josimar O.; Petrilli, Raquel; Topan, José Fernando; Antonio, Heriton Marcelo Ribeiro; Barcellos, Juliana Palma Abriata; Chesca, Deise L.; Serafini, Luciano Neder; Tiezzi, Daniel G.; Lee, Robert J.; Marchetti, Juliana Maldonado

    2016-01-01

    Paclitaxel and rapamycin have been reported to act synergistically to treat breast cancer. Albeit paclitaxel is available for breast cancer treatment, the most commonly used formulation in the clinic presents side effects, limiting its use. Furthermore, both drugs present pharmacokinetics drawbacks limiting their in vivo efficacy and clinic combination. As an alternative, drug delivery systems, particularly liposomes, emerge as an option for drug combination, able to simultaneously deliver co-loaded drugs with improved therapeutic index. Therefore, the purpose of this study is to develop and characterize a co-loaded paclitaxel and rapamycin liposome and evaluate it for breast cancer efficacy both in vitro and in vivo. Results showed that a SPC/Chol/DSPE-PEG (2000) liposome was able to co-encapsulate paclitaxel and rapamycin with suitable encapsulation efficiency values, nanometric particle size, low polydispersity and neutral zeta potential. Taken together, FTIR and thermal analysis evidenced drug conversion to the more bioavailable molecular and amorphous forms, respectively, for paclitaxel and rapamycin. The pegylated liposome exhibited excellent colloidal stability and was able to retain drugs encapsulated, which were released in a slow and sustained fashion. Liposomes were more cytotoxic to 4T1 breast cancer cell line than the free drugs and drugs acted synergistically, particularly when co-loaded. Finally, in vivo therapeutic evaluation carried out in 4T1-tumor-bearing mice confirmed the in vitro results. The co-loaded paclitaxel/rapamycin pegylated liposome better controlled tumor growth compared to the solution. Therefore, we expect that the formulation developed herein might be a contribution for future studies focusing on the clinical combination of paclitaxel and rapamycin. PMID:26836480

  7. Liposomal paclitaxel formulations.

    Science.gov (United States)

    Koudelka, Stěpán; Turánek, Jaroslav

    2012-11-10

    Over the past three decades, taxanes represent one of the most important new classes of drugs approved in oncology. Paclitaxel (PTX), the prototype of this class, is an anti-cancer drug approved for the treatment of breast and ovarian cancer. However, notwithstanding a suitable premedication, present-day chemotherapy employing a commercial preparation of PTX (Taxol®) is associated with serious side effects and hypersensitivity reactions. Liposomes represent advanced and versatile delivery systems for drugs. Generally, both in vivo mice tumor models and human clinical trials demonstrated that liposomal PTX formulations significantly increase a maximum tolerated dose (MTD) of PTX which outperform that for Taxol®. Liposomal PTX formulations are in various stages of clinical trials. LEP-ETU (NeoPharm) and EndoTAG®-1 (Medigene) have reached the phase II of the clinical trials; Lipusu® (Luye Pharma Group) has already been commercialized. Present achievements in the preparation of various liposomal formulations of PTX, the development of targeted liposomal PTX systems and the progress in clinical testing of liposomal PTX are discussed in this review summarizing about 30 years of liposomal PTX development.

  8. The Boron Efflux Transporter ROTTEN EAR Is Required for Maize Inflorescence Development and Fertility[C][W][OPEN

    Science.gov (United States)

    Chatterjee, Mithu; Tabi, Zara; Galli, Mary; Malcomber, Simon; Buck, Amy; Muszynski, Michael; Gallavotti, Andrea

    2014-01-01

    Although boron has a relatively low natural abundance, it is an essential plant micronutrient. Boron deficiencies cause major crop losses in several areas of the world, affecting reproduction and yield in diverse plant species. Despite the importance of boron in crop productivity, surprisingly little is known about its effects on developing reproductive organs. We isolated a maize (Zea mays) mutant, called rotten ear (rte), that shows distinct defects in vegetative and reproductive development, eventually causing widespread sterility in its inflorescences, the tassel and the ear. Positional cloning revealed that rte encodes a membrane-localized boron efflux transporter, co-orthologous to the Arabidopsis thaliana BOR1 protein. Depending on the availability of boron in the soil, rte plants show a wide range of phenotypic defects that can be fully rescued by supplementing the soil with exogenous boric acid, indicating that rte is crucial for boron transport into aerial tissues. rte is expressed in cells surrounding the xylem in both vegetative and reproductive tissues and is required for meristem activity and organ development. We show that low boron supply to the inflorescences results in widespread defects in cell and cell wall integrity, highlighting the structural importance of boron in the formation of fully fertile reproductive organs. PMID:25035400

  9. Boron film thickness determination to develop a low cost neutron using Monte Carlo method

    Energy Technology Data Exchange (ETDEWEB)

    Costa, Priscila; Raele, Marcus P.; Yoriyaz, Helio; Siqueira, Paulo de T.D.; Zahn, Guilherme S.; Genezini, Frederico A., E-mail: fredzini@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2015-07-01

    Neutron measurement is important for safety and security of workers at nuclear facilities. As neutron is an uncharged particle, for its detection is necessary to use a converter material that interacts with the neutron and produce a charged particle, which is easy to detect. One of the converter candidates is natural boron composed by about 20% of Boron-10, which capture a low energy neutron ejecting an energetic alpha particle and a lithium ion. A neutron detector can be developed applying a boron thin film over a silicon photodiode, which is charged particle sensitive. For this reason is important to determine the optimal film thickness. We have used an empirical solution for the boron film thickness evaluation; furthermore we developed, using Monte Carlo method (MCNP6), a model to simulate the alpha particles propagation through the detector. Our goal was to ensure the best production and transference of alpha particles to silicon region. The film thickness ranged between 0 to 5.5 μm, the neutron energy was also varied. The optimal thickness value will be used to develop a prototype of a low cost neutron detector. (author)

  10. Development of Cutting Tool Through Superplastic Boronizing of Duplex Stainless Steel

    Science.gov (United States)

    Jauhari, Iswadi; Harun, Sunita; Jamlus, Siti Aida; Sabri, Mohd Faizul Mohd

    2017-01-01

    In this study, a cutting tool is developed from duplex stainless steel (DSS) using the superplastic boronizing technique. The feasibility of the development process is studied, and the cutting performances of the cutting tool are evaluated and compared with commercially available carbide and high-speed steel (HSS) tools. The superplastically boronized (SPB) cutting tool yielded a dense boronized layer of 50.5 µm with a surface hardness of 3956 HV. A coefficient of friction value of 0.62 is obtained, which is lower than 1.02 and 0.8 of the carbide and HSS tools. When tested on an aluminum 6061 surface under dry condition, the SPB cutting tool is also able to produce turning finishing below 0.4 µm, beyond the travel distance of 3000 m, which is comparable to the carbide tool, but produces much better results than HSS tool. Through superplastic boronizing of DSS, it is possible to produce a high-quality metal-based cutting tool that is comparable to the conventional carbide tool.

  11. Development of Cutting Tool Through Superplastic Boronizing of Duplex Stainless Steel

    Science.gov (United States)

    Jauhari, Iswadi; Harun, Sunita; Jamlus, Siti Aida; Sabri, Mohd Faizul Mohd

    2017-03-01

    In this study, a cutting tool is developed from duplex stainless steel (DSS) using the superplastic boronizing technique. The feasibility of the development process is studied, and the cutting performances of the cutting tool are evaluated and compared with commercially available carbide and high-speed steel (HSS) tools. The superplastically boronized (SPB) cutting tool yielded a dense boronized layer of 50.5 µm with a surface hardness of 3956 HV. A coefficient of friction value of 0.62 is obtained, which is lower than 1.02 and 0.8 of the carbide and HSS tools. When tested on an aluminum 6061 surface under dry condition, the SPB cutting tool is also able to produce turning finishing below 0.4 µm, beyond the travel distance of 3000 m, which is comparable to the carbide tool, but produces much better results than HSS tool. Through superplastic boronizing of DSS, it is possible to produce a high-quality metal-based cutting tool that is comparable to the conventional carbide tool.

  12. Chitosan-aprotinin coated liposomes for oral peptide delivery: Development, characterisation and in vivo evaluation.

    Science.gov (United States)

    Werle, Martin; Takeuchi, Hirofumi

    2009-03-31

    In order to improve the systemic uptake of therapeutic peptides/proteins after oral administration, the polymer-protease inhibitor conjugate chitosan-aprotinin was synthesised and polyelectrolyte complexes between negatively charged multilamellar vesicles (MLV) and positively charged chitosan-aprotinin conjugate were prepared. It could be demonstrated that chitosan-aprotinin was capable of significantly inhibiting Trypsin in vitro in concentrations of 0.05% and 0.1%, whereas no inhibition was observed in the presence of 0.1% chitosan. The size range of the prepared MLV was between 3 and 4.5microm and the initially negative zeta potential (ca. -90mV) of the core liposomes switched to a positive value after polymer coating (ca. +40mV). Confocal laser microscopy studies showed comparable mucoadhesive properties of chitosan-aprotinin coated MLV and chitosan coated MLV. In comparison to calcitonin in solution, the area above the blood calcium concentration-time curve (AAC) after oral administration of calcitonin loaded chitosan coated MLV to rats increased around 11-fold, and around 15-fold in the case of calcitonin loaded chitosan-aprotinin coated MLV. Data gained in the current study are believed to contribute to the development of novel polymer-protease inhibitor based delivery systems.

  13. Clinical developments of chemotherapeutic nanomedicines: Polymers and liposomes for delivery of camptothecins and platinum (II) drugs

    KAUST Repository

    Kieler-Ferguson, Heidi M.

    2013-01-17

    For the past 40 years, liposomal and polymeric delivery vehicles have been studied as systems capable of modulating the cytotoxicity of small molecule chemotherapeutics, increasing tumor bearing animal survival times, and improving drug targeting. Although a number of macromolecular-drug conjugates have progressed to clinical trials, tuning drug release to maintain efficacy in conjunction with controlling drug toxicity has prevented the clinical adoption of many vehicles. In this article, we review the motivations for and approaches to polymer and liposomal delivery with regard to camptothecin and cisplatin delivery. WIREs Nanomed Nanobiotechnol 2013, 5:130-138. doi: 10.1002/wnan.1209 For further resources related to this article, please visit the WIREs website. Conflict of interest: Drs Kieler-Ferguson and Fréchet declare no conflicts of interest. Dr Szoka is the founder of a liposome drug delivery company that is not working on any of the compounds mentioned in this article. © 2013 Wiley Periodicals, Inc.

  14. Development of nanoparticles incorporating a novel liposomal membrane destabilization peptide for efficient release of cargos into cancer cells.

    Directory of Open Access Journals (Sweden)

    Shoko Itakura

    Full Text Available In anti-cancer therapy mediated by a nanoparticle-based drug delivery system (DDS, overall efficacy depends on the release efficiency of cargos from the nanoparticles in the cancer cells as well as the specificity of delivery to tumor tissue. However, conventional liposome-based DDS have no mechanism for specifically releasing the encapsulated cargos inside the cancer cells. To overcome this barrier, we developed nanoparticles containing a novel liposomal membrane destabilization peptide (LMDP that can destabilize membranes by cleavage with intramembranous proteases on/in cancer cells. Calcein encapsulated in liposomes modified with LMDP (LMDP-lipo was effectively released in the presence of a membrane fraction containing an LMDP-cleavable protease. The release was inhibited by a protease inhibitor, suggesting that LMDP-lipo could effectively release its cargo into cells in response to a cancer-specific protease. Moreover, when LMDP-lipo contained fusogenic lipids, the release of cargo was accelerated, suggesting that the fusion of LMDP-lipo with cellular membranes was the initial step in the intracellular delivery. Time-lapse microscopic observations showed that the release of cargo from LMDP-lipo occurred immediately after association of LMDP-lipo with target cells. Consequently, LMDP-lipo could be a useful nanoparticle capable of effective release of cargos specifically into targeted cancer cells.

  15. Clinical developments of chemotherapeutic nanomedicines: polymers and liposomes for delivery of camptothecins and platinum (II) drugs.

    Science.gov (United States)

    Kieler-Ferguson, Heidi M; Fréchet, Jean M J; Szoka, Francis C

    2013-01-01

    For the past 40 years, liposomal and polymeric delivery vehicles have been studied as systems capable of modulating the cytotoxicity of small molecule chemotherapeutics, increasing tumor bearing animal survival times, and improving drug targeting. Although a number of macromolecular-drug conjugates have progressed to clinical trials, tuning drug release to maintain efficacy in conjunction with controlling drug toxicity has prevented the clinical adoption of many vehicles. In this article, we review the motivations for and approaches to polymer and liposomal delivery with regard to camptothecin and cisplatin delivery.

  16. Application of Response Surface Methodology in Development of Sirolimus Liposomes Prepared by Thin Film Hydration Technique

    Directory of Open Access Journals (Sweden)

    Saeed Ghanbarzadeh

    2013-04-01

    Full Text Available Introduction: The present investigation was aimed to optimize the formulating process of sirolimus liposomes by thin film hydration method. Methods: In this study, a 32 factorial design method was used to investigate the influence of two independent variables in the preparation of sirolimus liposomes. The dipalmitoylphosphatidylcholine (DPPC /Cholesterol (Chol and dioleoyl phosphoethanolamine(DOPE /DPPC molar ratios were selected as the independent variables. Particle size (PS and Encapsulation Efficiency (EE % were selected as the dependent variables. To separate the un-encapsulated drug, dialysis method was used. Drug analysis was performed with a validated RP-HPLC method. Results: Using response surface methodology and based on the coefficient values obtained for independent variables in the regression equations, it was clear that the DPPC/Chol molar ratio was the major contributing variable in particle size and EE %. The use of a statistical approach allowed us to see individual and/or interaction effects of influencing parameters in order to obtain liposomes with desired properties and to determine the optimum experimental conditions that lead to the enhancement of characteristics. In the prediction of PS and EE % values, the average percent errors are found to be as 3.59 and 4.09%. This value is sufficiently low to confirm the high predictive power of model. Conclusion: Experimental results show that the observed responses were in close agreement with the predicted values and this demonstrates the reliability of the optimization procedure in prediction of PS and EE % in sirolimus liposomes preparation.

  17. LIPOSOMES: AN OVERVIEW

    Directory of Open Access Journals (Sweden)

    Sipai Altaf Bhai. M

    2012-02-01

    Full Text Available Drug development technologies constituting innovations at the formulation end in the Pharmaceutical industry has received a lot of attention in past two decades. Drug delivery as an opportunity to extend product life cycles has indeed proved its place in the market with significant advantages of therapeutic gains as well as commercial success. Carrier technology offers an intelligent approach for drug delivery by coupling the drug to a carrier particle such as liposomes, microspheres, nanoparticles, etc. which modulates the release and absorption characteristics of the drug. Liposomes are well known to alter the bio distribution of entrapped substances by protecting the enclosed material. They are widely used as vehicles to target the specific molecule to specific organ. During the last few decades liposomes have attracted great interest as ideal models for biological membranes as well as efficient carriers for drugs, diagnostics, vaccines, nutrients and other bioactive agents. Many techniques and methodologies have involved for the manufacture of liposomes, on small and large scales, since their introduction to the scientific community around 40 years ago. This article intends to provide an overview of the advantages and disadvantages of liposome preparation methods,their stability, bio distribution and their uses as drug delivery systems. The conventional method of preparing liposomes is basically for the multilamellar vesicles (MLVs. However, other methods are used to reduce the size of these MLVs to small unilamellar vesicles (SUVs so as to increase their plasma lifetime and consequently increase the possibility of achieving greater tissue localisation. Some of these methods of size reduction are sonication and high pressure extrusion. Each of these methods has its own advantages and disadvantages. Large unilamellar vesicles (LUVs, on the other hand, are prepared mainly by detergent removal method and reverse phase extrusion technique. There

  18. Flurbiprofen-Loaded Stealth Liposomes: Studies on the Development, Characterization, Pharmacokinetics, and Biodistribution

    Science.gov (United States)

    Begum, MY; Abbulu, K; Sudhakar, M

    2012-01-01

    Flurbiprofen (FP) is a phenyl alkanoic acid derivative and a family of non–steroidal anti-inflammatory drug used in the treatment of arthritis. The aim of this study was to prepare a new parenteral formulation for FP that can prolong the biologic half-life of the drug, improve its therapeutic efficacy, and reduce its associated side effects targeting the inflammation due to arthritis. PEG-anchored (stealth) and non–PEG-anchored liposomes were prepared by thin film hydration technique followed by extrusion cycle and characterized for in vitro and in vivo. Stealth liposomes (SLs) exhibited increase in percent encapsulation efficiency (68%) and percent drug retention during release studies in 24 h (71%) with good stability for a period of 1 month at –20°C and 4°C (refrigerated temperature) compared with other liposomes. The maximum percent edema inhibition (58%) and significant analgesic effect of 13 s were determined for SLs. The pharmacokinetic parameters after i.v. administration to arthritis induced rats were determined and compared with non-SLs. The marked differences produced for SLs over those of non-SL (conventional) formulations with an increase in area under plasma concentration time curve, t1/2, mean residence time, and reduced clearance. The drug localization in liver, spleen, and kidney were significantly higher for non-PEGylated liposomes than the SLs. Nearly 3-fold increase in drug concentration was measured in arthritic paw when compared with the other liposome formulations. Thus SLs may help to increase the therapeutic efficacy of FP by increasing the targeting potential at the site of action. PMID:23493109

  19. Science and technology in the recent development of boron nitride materials

    CERN Document Server

    Fukunaga, O

    2002-01-01

    In this paper, we review recent developments relating to cubic boron nitride (cBN) abrasive grains and sintered cutting tools. The demand for high-speed machining and the ecological benefits of using ferrous materials have led to developments in the area of heavy-duty dry cutting and grinding processes in recent years. Optimization of the process of manufacturing cBN materials is an important issue, both fundamentally and as regards applications. We review recent developments in cBN applications and discuss the challenges arising from new processes encountered in basic cBN study at high pressure and high temperature.

  20. Development of boron carbide-copper cermets. Status report

    Energy Technology Data Exchange (ETDEWEB)

    1979-09-01

    The status of a program to develop a B/sub 4/C-Cu cermet for Breeder Reactor spent-fuel shipping cask neutron shields is presented. It is shown that inspectable 6 to 7 cm thick 60 to 70 volume percent B/sub 4/C cermets can be fabricated using hot isostatic powder processing procedures. An alternative manufacturing method, rheocasting, also appears to be a promising, perhaps more cost-effective method for producing these cermets. Recommendations for further development of these manufacturing processes are given.

  1. Development of Silicon Drift Detectors using Boron layer technology

    NARCIS (Netherlands)

    Golshani, N.

    2015-01-01

    Radiation detectors are used in a large variety of fields such as medicine, security, defense, geophysics, industry and physics. They have been developed to detect the energy or position of radiation or charge particles. In Chapter 1 several X-ray detectors were introduced briefly. In gas filled X

  2. Development of liposomal Ganoderma lucidum polysaccharide: formulation optimization and evaluation of its immunological activity.

    Science.gov (United States)

    Liu, Zhenguang; Ma, Xia; Deng, Bihua; Huang, Yee; Bo, Ruonan; Gao, Zhenzhen; Yu, Yun; Hu, Yuanliang; Liu, Jiaguo; Wu, Yi; Wang, Deyun

    2015-03-01

    The aim of this study was to investigate the optimizing preparation conditions of Ganoderma lucidum polysaccharide liposome (GLPL) with response surface methodology (RSM) and the immunological enhancement activity of GLPL. The immunological enhancement activity of GLPL on splenocyte proliferation was measured. The optimum formulation of GLPL, in which the ratio of soybean phospholipid to cholesterol(w/w) of 11:1, the ratio of soybean phospholipid to tween-80 (w/w) of 10.5:1 and ultrasonic time(min) of 11, had higher entrapment efficiency (EE) of 71.43±0.49% with spherical shape and uniform sizes. In addition, GLPL could significantly promote splenocyte proliferation singly or synergistically with PHA and LPS. That indicated that the immunological enhancement of Ganoderma lucidum polysaccharide (GLP) was significantly enhanced after encapsulation with the liposome.

  3. Development of Silicon Drift Detectors using Boron layer technology

    OpenAIRE

    2015-01-01

    Radiation detectors are used in a large variety of fields such as medicine, security, defense, geophysics, industry and physics. They have been developed to detect the energy or position of radiation or charge particles. In Chapter 1 several X-ray detectors were introduced briefly. In gas filled X-ray detectors, incoming photons ionize inert gas and create electron and ions which can be collected at a thin wire anode inside of the chamber. The advantage of this type of detector is the possibi...

  4. Development of edge-activated liposomes for siRNA delivery to human basal epidermis for melanoma therapy.

    Science.gov (United States)

    Dorrani, Mania; Garbuzenko, Olga B; Minko, Tamara; Michniak-Kohn, Bozena

    2016-04-28

    Delivery of macromolecules such as siRNA into cells that reside in the basal epidermis of the skin is a major challenge due to the transport barriers that need to be overcome. siRNAs have potential therapeutic applications in various dermatological diseases such as psoriasis, atopic dermatitis, and cancer. Unfortunately, a low permeability of siRNA through the stratum corneum and epidermis has significantly limited its use for topical application. The objective of this study was to develop a topical siRNA delivery system that can permeate through the stratum corneum and viable epidermis and efficiently deposit therapeutic levels of siRNA to the basal epidermis/upper dermis where melanoma cells reside. To achieve this objective, a series of liposome compositions that contained various concentrations of edge activator in their structures were prepared and then complexed with siRNA at different ratios to generate a small library of liposome-siRNA complexes (lipoplexes) with different physicochemical properties. In this study we used melanoma as a disease model. Through use of quantitative imaging analysis, we identified the necessary design parameters for effective permeation of lipoplexes through the skin layers and deposition at the upper dermis. The ability of the formulated lipoplexes to internalize into melanoma cells, knockdown the expression of the BRAF protein and induce cell death in melanoma cells was studied by fluorescent microscopy, in-cell immunofluorescence assay and WST-1 cell proliferation assay. By providing direct quantitative and qualitative microscopy evidence, the results of this study demonstrate for the first time that the passive delivery of an edge-activated liposomal formulation can effectively carry siRNA through the stratum corneum and deposit it at the lower epidermis/upper dermis.

  5. Development and construction of a neutron beam line for accelerator-based boron neutron capture synovectomy.

    Science.gov (United States)

    Gierga, D P; Yanch, J C; Shefer, R E

    2000-01-01

    A potential application of the 10B(n, alpha)7Li nuclear reaction for the treatment of rheumatoid arthritis, termed Boron Neutron Capture Synovectomy (BNCS), is under investigation. In an arthritic joint, the synovial lining becomes inflamed and is a source of great pain and discomfort for the afflicted patient. The goal of BNCS is to ablate the synovium, thereby eliminating the symptoms of the arthritis. A BNCS treatment would consist of an intra-articular injection of boron followed by neutron irradiation of the joint. Monte Carlo radiation transport calculations have been used to develop an accelerator-based epithermal neutron beam line for BNCS treatments. The model includes a moderator/reflector assembly, neutron producing target, target cooling system, and arthritic joint phantom. Single and parallel opposed beam irradiations have been modeled for the human knee, human finger, and rabbit knee joints. Additional reflectors, placed to the side and back of the joint, have been added to the model and have been shown to improve treatment times and skin doses by about a factor of 2. Several neutron-producing charged particle reactions have been examined for BNCS, including the 9Be(p,n) reaction at proton energies of 4 and 3.7 MeV, the 9Be(d,n) reaction at deuteron energies of 1.5 and 2.6 MeV, and the 7Li(p,n) reaction at a proton energy of 2.5 MeV. For an accelerator beam current of 1 mA and synovial boron uptake of 1000 ppm, the time to deliver a therapy dose of 10,000 RBEcGy ranges from 3 to 48 min, depending on the treated joint and the neutron producing charged particle reaction. The whole-body effective dose that a human would incur during a knee treatment has been estimated to be 3.6 rem or 0.75 rem, for 1000 ppm or 19,000 ppm synovial boron uptake, respectively, although the shielding configuration has not yet been optimized. The Monte Carlo design process culminated in the construction, installation, and testing of a dedicated BNCS beam line on the high

  6. Physicochemical characterization of asulacrine towards the development of an anticancer liposomal formulation via active drug loading: stability, solubility, lipophilicity and ionization.

    Science.gov (United States)

    See, Esther; Zhang, Wenli; Liu, Jianping; Svirskis, Darren; Baguley, Bruce C; Shaw, John P; Wang, Guangji; Wu, Zimei

    2014-10-01

    To facilitate the development of a liposomal formulation for cancer therapy, the physicochemical properties of asulacrine (ASL), an anticancer drug candidate, were characterized. Nano-liposomes were prepared by thin-film hydration in conjugation with active drug loading using ammonium sulphate and post-insertion with Poloxamer 188. A stability-indicating HPLC assay with diode array detection was developed for the determination of ASL concentrations. The U-shaped pH-solubility profile in aqueous solutions, with a lowest solubility at pH 7.4 (0.843 μg/mL), indicated that ASL is an ampholyte, and dilution or neutralization of acidic drug solutions used in clinical trials with physiological fluids may cause drug precipitation. The basic pKa value measured by absorbance spectroscopy was 6.72. The logD value at pH 3.8 was 1.15 which increased to 3.24 as pH increased to 7.4. ASL was found to be the most stable in acidic conditions and degraded most rapidly in alkaline conditions. An extra-liposomal pH of 5.6 during drug loading was found to be optimal to achieve the highest drug loading (DL) of 4.76% and entrapment efficiency (EE) of 99.9%. At this pH, >90% of ASL was ionized conferring high drug solubility (1mg/mL) and acted as a reservoir of unionized ASL to be transported into liposomal cores. As a suspension the optimized liposomes showed great physicochemical stability for five months at 4°C. In summary, the obtained physicochemical parameters provided insightful information useful to maximise DL into the liposomes, and explain a tendency of drug precipitation of pH-solubilized formulations following intravenous infusion.

  7. Development of Liposomal Formulation for Delivering Anticancer Drug to Breast Cancer Stem-Cell-Like Cells and its Pharmacokinetics in an Animal Model.

    Science.gov (United States)

    Ahmad, Ajaz; Mondal, Sujan Kumar; Mukhopadhyay, Debabrata; Banerjee, Rajkumar; Alkharfy, Khalid M

    2016-03-07

    The objective of the present study is to develop a liposomal formulation for delivering anticancer drug to breast cancer stem-cell-like cells, ANV-1, and evaluate its pharmacokinetics in an animal model. The anticancer drug ESC8 was used in dexamethasone (Dex)-associated liposome (DX) to form ESC8-entrapped liposome named DXE. ANV-1 cells showed high-level expression of NRP-1. To enhance tumor regression, we additionally adapted to codeliver the NRP-1 shRNA-encoded plasmid using the established DXE liposome. In vivo efficacy of DXE-NRP-1 was carried out in mice bearing ANV-1 cells as xenograft tumors and the extent of tumor growth inhibition was evaluated by tumor-size measurement. A significant difference in tumor volume started to reveal between DXE-NRP-1 group and DXE-Control group. DXE-NRP-1 group showed ∼4 folds and ∼2.5 folds smaller tumor volume than exhibited by untreated and DXE-Control-treated groups, respectively. DXE disposition was evaluated in Sprague-Dawley rats following an intraperitoneal dose (3.67 mg/kg of ESC8 in DXE). The plasma concentrations of ESC8 in the DXE formulation were measured by liquid chromatography mass spectrometry and pharmacokinetic parameters were determined using a noncompartmental analysis. ESC8 had a half-life of 11.01 ± 0.29 h, clearance of 2.10 ± 3.63 L/kg/h, and volume of distribution of 33.42 ± 0.83 L/kg. This suggests that the DXE liposome formulation could be administered once or twice daily for therapeutic efficacy. In overall, we developed a potent liposomal formulation with favorable pharmacokinetic and tumor regressing profile that could sensitize and kill highly aggressive and drug-resistive cancer stem-cell-like cells.

  8. LIPOSOME AS A POTENTIAL DRUG DELIVERY SYSTEM: A REVIEW

    Directory of Open Access Journals (Sweden)

    Dash Tapaswi Rani

    2013-01-01

    Full Text Available Liposomes are microscopic phospholipid vescicles made of lipid bilayer which are the drug carrier for improving the delivery of therapeutic agents. Research on liposome technology has progressed from conventional vesicles (“first-generation liposomes” to “second-generation liposomes”, in which long-circulating liposomes are obtained by modulating the lipid composition, size, and charge of the vesicle. Liposomes with modified surfaces have also been developed using several molecules, such as glycolipids or sialic acid. A significant step in the development of long-circulating liposomes came with inclusion of the synthetic polymer poly-(ethylene glycol (PEG in liposome composition. Due to advancement in liposomal technology a number of liposomal formulations are available in market for clinical use, with gene delivery and cancer therapy and some formulations are under clinical trial. Reformulation of drugs in liposomes has provided an opportunity to enhance the therapeutic indices of various agents mainly through alteration in their biodistribution. This review discusses the basic principles of liposome structures and preparations, evaluation parameters of liposomal formulation, pharmacokinetics of liposomes and liposome-encapsulated drugs, the potential applications of liposomes in drug delivery with examples of formulations approved for clinical use, and the problems associated with further exploitation of this drug delivery system.

  9. Development and pharmacokinetic of antimony encapsulated in liposomes of phosphatidylserine using radioisotopes in experimental leishmaniasis; Desenvolvimento e farmacocinetica de antimonio encapsulado em lipossomas de fosfatidilserina utilizando radioisotopos em leishmaniose experimental

    Energy Technology Data Exchange (ETDEWEB)

    Borborema, Samanta Etel Treiger

    2010-07-01

    Leishmaniasis are a complex of parasitic diseases caused by intra macrophage protozoa of the genus Leishmania, and is fatal if left untreated. Pentavalent antimonials, though toxic and their mechanism of action being unclear, remain the first-line drugs for treatment. Effective therapy could be achieved by delivering antileishmanial drugs to these sites of infection. Liposomes are phospholipid vesicles that promote improvement in the efficacy and action of drugs in target cell. Liposomes are taken up by the cells of mononuclear phagocytic system (MPS). The purpose of this study was to develop a preparation of meglumine antimonate encapsulated in liposomes of phosphatidylserine and to study its pharmacokinetic in healthy mice to establish its metabolism and distribution. Quantitative analysis of antimony from liposomes demonstrated that Neutron Activation Analysis was the most sensitive technique with almost 100 % of accuracy. All liposome formulations presented a mean diameter size of 150 nm. The determination of IC{sub 50} in infected macrophage showed that liposome formulations were between 10 - 63 fold more effective than the free drug, indicating higher selectivity index. By fluorescence microscopy, an increased uptake of fluorescent-liposomes was seen in infected macrophages during short times of incubation compared with non-infected macrophages. Biodistribution studies showed that meglumine antimonate irradiated encapsulated in liposomes of phosphatidylserine promoted a targeting of antimony for MPS tissues and maintained high doses in organs for a prolonged period. In conclusion, these data suggest that meglumine antimonate encapsulated in liposomes showed higher effectiveness than the non-liposomal drug against Leishmania infection. The development of liposome formulations should be a new alternative for the chemotherapy of infection diseases, especially Leishmaniasis, as they are used to sustain and target pharmaceuticals to the local of infection. (author)

  10. Complement activation as a bioequivalence issue relevant to the development of generic liposomes and other nanoparticulate drugs

    NARCIS (Netherlands)

    Szebeni, Janos; Storm, G

    2015-01-01

    Liposomes are known to activate the complement (C) system, which can lead in vivo to a hypersensitivity syndrome called C activation-related pseudoallergy (CARPA). CARPA has been getting increasing attention as a safety risk of i.v. therapy with liposomes, whose testing is now recommended in bioequi

  11. EXPERIMENTAL LIPOSOMAL VIRAL VACCINE SAFETY

    Directory of Open Access Journals (Sweden)

    Romanova OA

    2016-12-01

    Full Text Available Introduction. With the transport links development there is rather important issue respiratory viral infections spread, especially influenza. The only method controlling influenza is vaccination. Search and development effective and safe vaccines is important. Material and methods. In base SO "Mechnikov Institute Microbiology and Immunology National Ukrainian Academy Medical Sciences" in the scientific theme "Developing new approaches to creating viral vaccines and study specific activity depending of type and degree component`s modification" was created several experimental influenza vaccine with subsequent component`s modification for selecting the most optimal pattern of safety and immunogenicity. In assessing the influenza vaccine safety is using a few criteria, including, reactivity, as measured by the frequency of local and systemic adverse (negative effects, which due to its introduction, and for lipid content drugs, ability to influence oxidation processes. At present study phase was determined: a systemic reaction and local reaction of delayed-type hypersensitivity (foot pad swelling assay;b lipids and proteins peroxidation processes after administration officinal and experimental vaccines (content protein’s carbonyl groups, lipid’s hydroperoxides, activity of glutathione-peroxidase.Study objects were trivalent seasonal influenza vaccine, "Vaxigrip" (Sanofi Pasteur, S.A., France, "Inflexal V" (Biotech Ltd. Berne, Switzerland and experimental vaccine samples. Highest immunogenicity vaccines had undergone improvements and modifications using adjuvant systems and acylation influenza proteins. Liposomes 2 – the experimental influenza vaccine with a liposome negative charge and antigenic composition like split vaccines "Vaksihryp". Liposomes 2.1 - the adjuvantexperimental influenza vaccine with modifications liposomal components (etoniy and chlorophyllipt molecules embedded in liposomal membrane. Liposomes 2.2 - the adjuvant

  12. Lysolipid containing liposomes for transendothelial drug delivery

    Directory of Open Access Journals (Sweden)

    Koklic Tilen

    2012-04-01

    Full Text Available Abstract Background Designing efficient 'vectors', to deliver therapeutics across endothelial barriers, in a controlled manner, remains one of the key goals of drug development. Recently, transcytosis of liposome encapsulated fluorescence marker calcein across a tight cell barrier was studied. The most efficient liposomes were found to be liposomes containing sufficient amount of alkyl phospholipid (APL perifosine. APLs have similar structure as lysophosphatidyl choline (LPC, since APLs were synthesized as metabolically stable analogues of LPC, which increases endothelial permeability directly by inducing endothelial cell contraction, resulting in formation of gaps between endothelial cells. Since one of the unique properties of lysolipid, containing liposomal formulations is dynamic equilibrium of lysolipids, which are distributed among liposomes, micelles, and free form, such liposomes represent a reservoir of free lysolipids. On the other hand lysolipid containing liposomes also represent a reservoir of an encapsulated hydrophilic drug. Presentation of the hypothesis We hypothesize that free lysolipids, with highest concentration in vicinity of drug carrying liposomes, compromise endothelial integrity, primarily where concentrations of liposomes is the highest, in a similar manner as LPC, by formation of gaps between endothelial cells. Liposome encapsulated drug, which leaks from liposomes, due to liposome destabilization, caused by lysolipid depletion, can therefore be efficiently transported across the locally compromised endothelial barrier. Testing the hypothesis This hypothesis could be verified: by measuring binding of perifosine and other lysolipids to albumin and to lysophospholipid receptor (LPL-R group; formation of stress fibers and subsequent cell contraction; activation of RhoA, and endothelial barrier dysfunction; by a synthesis of other LPC analogues with high critical micellar concentration and measuring their effect on

  13. Liposomal amphotericin B for the treatment of visceral leishmaniasis

    OpenAIRE

    Bern, C.; Adler-Moore, J.; Berenguer, J.; Boelaert, M; van den Boer, M.; Davidson, R N; Figueras, C; Gradoni, L.; Kafetzis, D. A.; Ritmeijer, E.; Rosenthal, E.; Royce, C; Russo, R; Sundar, S; Alvar, J.

    2006-01-01

    During the past decade, liposomal amphotericin B has been used with increasing frequency to treat visceral leishmaniasis (VL). The World Health Organization convened a workshop to review current knowledge and to develop guidelines for liposomal amphotericin B use for VL. In Europe, liposomal amphotericin B is widely used to treat VL. In Africa and Asia, the VL disease burden is high and drug access is poor; liposomal amphotericin B is available only through preferential pricing for nonprofit ...

  14. Liposomal dry powders as aerosols for pulmonary delivery of proteins

    OpenAIRE

    Lu, Dongmei; Hickey, Anthony J.

    2005-01-01

    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...

  15. Development of tea tree oil-loaded liposomal formulation using response surface methodology.

    Science.gov (United States)

    Ge, Yan; Ge, Mingqiao

    2015-03-23

    The aim of this study is to prepare tea tree oil liposome (TTOL) and optimize the preparation condition by single factor experiment and statistical design. TTOL was prepared using a thin-film hydration with the combination of sonication method and the preparation conditions of TTOL were optimized with response surface methodology (RSM). The optimal preparation conditions for TTOL by response surface methodology were as follows: the mass ratio of PC and Cho 5.51, TTO concentration 1.21% (v/v) and Tween 80 concentration 0.79% (v/v). The response surface analysis showed that the significant (p  0.05) lack of fit for the reduced models. Furthermore, the interaction of the mass ratio of PC/Cho and TTO concentration had a significant effect. The amounts of Tween 80 required were also reduced with RSM. Under these conditions, the experimental encapsulation efficiency of TTOL was 97.81 ± 0.33%, which was close with the predicted value. Therefore, the optimized preparation condition was very reliable. The increased entrapment efficiency would significantly improve the TTO stability and bioavailability.

  16. Pharmacokinetics of temoporfin-loaded liposome formulations: correlation of liposome and temoporfin blood concentration.

    Science.gov (United States)

    Decker, Christiane; Schubert, Harald; May, Sylvio; Fahr, Alfred

    2013-03-28

    Liposomal formulations of the highly hydrophobic photosensitizer temoporfin were developed in order to overcome solubility-related problems associated with the current therapy scheme. We have incorporated temoporfin into liposomes of varying membrane composition, cholesterol content, and vesicle size. Specifically, two phosphatidyl oligoglycerols were compared to PEG2000-DSPE with respect to the ability to prolong circulation half life of the liposomal carrier. We measured the resulting pharmacokinetic profile of the liposomal carrier and the incorporated temoporfin in a rat model employing a radioactive lipid label and (14)C-temoporfin. The data for the removal of liposomes and temoporfin were analyzed in terms of classical pharmacokinetic theory assuming a two-compartment model. This model, however, does not allow in a straightforward manner to distinguish between temoporfin eliminated together with the liposomal carrier and temoporfin that is first transferred to other blood components (e. g. plasma proteins) before being eliminated from the blood. We therefore additionally analyzed the data based on two separate one-compartment models for the liposomes and temoporfin. The model yields the ratio of the rate constant of temoporfin elimination together with the liposomal carrier and the rate constant of temoporfin elimination following the transfer to e. g. plasma proteins. Our analysis using this model demonstrates that a fraction of temoporfin is released from the liposomes prior to being eliminated from the blood. In case of unmodified liposomes this temoporfin release was observed to increase with decreasing bilayer fluidity, indicating an accelerated temoporfin transfer from gel-phase liposomes to e. g. plasma proteins. Interestingly, liposomes carrying either one of the three investigated surface-modifying agents did not adhere to the tendencies observed for unmodified liposomes. Although surface-modified liposomes exhibited improved pharmacokinetic

  17. "Smart" liposomal nanocontainers in biology and medicine.

    Science.gov (United States)

    Tarahovsky, Y S

    2010-07-01

    The perspectives of using liposomes for delivery of drugs to desired parts of the human body have been intensively investigated for more than 30 years. During this time many inventions have been suggested and different kinds of liposomal devices developed, and a number of them have reached the stages of preclinical or clinical trials. The latest techniques can be used to develop biocompatible nano-sized liposomal containers having some abilities of artificial intellect, such as the presence of sensory and responsive units. However, only a few have been clinically approved. Further improvements in this area depend on our knowledge of the interactions of drugs with the lipid bilayer of liposomes. Further studies on liposomal transport through the human body, their targeting of cells requiring therapeutic treatment, and finally, the development of techniques for controlled drug delivery to desired acceptors on cell surfaces or in cytoplasm are still required.

  18. Development of Enantiospecific Coupling of Secondary and Tertiary Boronic Esters with Aromatic Compounds

    Science.gov (United States)

    2016-01-01

    The stereospecific cross-coupling of secondary boronic esters with sp2 electrophiles (Suzuki–Miyaura reaction) is a long-standing problem in synthesis, but progress has been achieved in specific cases using palladium catalysis. However, related couplings with tertiary boronic esters are not currently achievable. To address this general problem, we have focused on an alternative method exploiting the reactivity of a boronate complex formed between an aryl lithium and a boronic ester. We reasoned that subsequent addition of an oxidant or an electrophile would remove an electron from the aromatic ring or react in a Friedel–Crafts-type manner, respectively, generating a cationic species, which would trigger 1,2-migration of the boron substituent, creating the new C–C bond. Elimination (preceded by further oxidation in the former case) would result in rearomatization giving the coupled product stereospecifically. Initial work was examined with 2-furyllithium. Although the oxidants tested were unsuccessful, electrophiles, particularly NBS, enabled the coupling reaction to occur in good yield with a broad range of secondary and tertiary boronic esters, bearing different steric demands and functional groups (esters, azides, nitriles, alcohols, and ethers). The reaction also worked well with other electron-rich heteroaromatics and 6-membered ring aromatics provided they had donor groups in the meta position. Conditions were also found under which the B(pin)- moiety could be retained in the product, ortho to the boron substituent. This protocol, which created a new C(sp2)–C(sp3) and an adjacent C–B bond, was again applicable to a range of secondary and tertiary boronic esters. In all cases, the coupling reaction occurred with complete stereospecificity. Computational studies verified the competing processes involved and were in close agreement with the experimental observations. PMID:27384259

  19. Development of Enantiospecific Coupling of Secondary and Tertiary Boronic Esters with Aromatic Compounds.

    Science.gov (United States)

    Odachowski, Marcin; Bonet, Amadeu; Essafi, Stephanie; Conti-Ramsden, Philip; Harvey, Jeremy N; Leonori, Daniele; Aggarwal, Varinder K

    2016-08-03

    The stereospecific cross-coupling of secondary boronic esters with sp(2) electrophiles (Suzuki-Miyaura reaction) is a long-standing problem in synthesis, but progress has been achieved in specific cases using palladium catalysis. However, related couplings with tertiary boronic esters are not currently achievable. To address this general problem, we have focused on an alternative method exploiting the reactivity of a boronate complex formed between an aryl lithium and a boronic ester. We reasoned that subsequent addition of an oxidant or an electrophile would remove an electron from the aromatic ring or react in a Friedel-Crafts-type manner, respectively, generating a cationic species, which would trigger 1,2-migration of the boron substituent, creating the new C-C bond. Elimination (preceded by further oxidation in the former case) would result in rearomatization giving the coupled product stereospecifically. Initial work was examined with 2-furyllithium. Although the oxidants tested were unsuccessful, electrophiles, particularly NBS, enabled the coupling reaction to occur in good yield with a broad range of secondary and tertiary boronic esters, bearing different steric demands and functional groups (esters, azides, nitriles, alcohols, and ethers). The reaction also worked well with other electron-rich heteroaromatics and 6-membered ring aromatics provided they had donor groups in the meta position. Conditions were also found under which the B(pin)- moiety could be retained in the product, ortho to the boron substituent. This protocol, which created a new C(sp(2))-C(sp(3)) and an adjacent C-B bond, was again applicable to a range of secondary and tertiary boronic esters. In all cases, the coupling reaction occurred with complete stereospecificity. Computational studies verified the competing processes involved and were in close agreement with the experimental observations.

  20. Radioprotective effect of transferrin targeted citicoline liposomes.

    Science.gov (United States)

    Suresh Reddy, Jannapally; Venkateswarlu, Vobalaboina; Koning, Gerben A

    2006-01-01

    The high level of expression of transferrin receptors (Tf-R) on the surface of endothelial cells of the blood-brain-barrier (BBB) had been widely utilized to deliver drugs to the brain. The primary aim of this study was to use transferrin receptor mediated endocytosis as a pathway for the rational development of holo-transferrin coupled liposomes for drug targeting to the brain. Citicoline is a neuroprotective agent used clinically to treat for instance Parkinson disease, stroke, Alzheimer's disease and brain ischemia. Citicoline does not readily cross the BBB because of its strong polar nature. Hence, citicoline was used as a model drug. (Citicoline liposomes have been prepared using dipalmitoylphosphatidylcholine (DPPC) or distearoylphosphatidylcholine (DSPC) by dry lipid film hydration-extrusion method). The effect of the use of liposomes composed of DPPC or DSPC on their citicoline encapsulation efficiency and their stability in vitro were studied. Transferrin was coupled to liposomes by a technique which involves the prevention of scavenging diferric iron atoms of transferrin. The coupling efficiency of transferrin to the liposomes was studied. In vitro evaluation of transferrin-coupled liposomes was performed for their radioprotective effect in radiation treated cell cultures. In this study, OVCAR-3 cells were used as a model cell type over-expressing the Tf-R and human umbilical vein endothelial cells (HUVEC) as BBB endothelial cell model. The average diameter of DPPC and DSPC liposomes were 138 +/- 6.3 and 79.0 +/- 3.2 nm, respectively. The citicoline encapsulation capacity of DPPC and DSPC liposomes was 81.8 +/- 12.8 and 54.9 +/- 0.04 microg/micromol of phospholipid, respectively. Liposomes prepared from DSPC showed relatively better stability than DPPC liposomes at 37 degrees C and in the presence of serum. Hence, DSPC liposomes were used for transferrin coupling and an average of 46-55 molecules of transferrin were present per liposome. Free citicoline

  1. Development of a cavity ring-down spectroscopy sensor for boron nitride sputter erosion in Hall thrusters

    CERN Document Server

    Tao, Lei; Gallimore, Alec D; Yalin, Azer P

    2010-01-01

    Sputter erosion of boron nitride (BN) is a critically important process in Hall thrusters from the point of view of both lifetime assessment and contamination effects. This contribution describes the development of a laser based sensor for in situ monitoring of sputtered BN from Hall thrusters. We present a continuous-wave cavity ring-down spectroscopy (cw-CRDS) system and its demonstrative measurement results from BN sputtering experiments.

  2. Development of JCDS, a computational dosimetry system at JAEA for boron neutron capture therapy

    Science.gov (United States)

    Kumada, H.; Yamamoto, K.; Matsumura, A.; Yamamoto, T.; Nakagawa, Y.

    2007-06-01

    Clinical trials of boron neutron capture therapy (BNCT) are being carried out using several research reactors throughout the world. In Japan, many medical groups perform clinical trials of BNCT using Japan Research Reactor No.4 (JRR-4) in Japan Atomic Energy Agency (JAEA). JAEA has developed a treatment planning system, JCDS, in order to evaluate radiation dose given to a patient in the BNCT. JCDS employs a voxel calculation method to compute the radiation dose given to a patient. An initial version of JCDS created a voxel model, dividing a space into 1 × 1 × 1 cm3voxel cells. JCDS was improved to create a detailed voxel model consisting of minute voxel cells such as 2 × 2 × 2 mm3voxel cells. Verification of accuracy of calculations with the detailed voxel mode demonstrated that the detailed voxel model enables JCDS to evaluate more accurately the radiation doses to a patient undergoing BNCT. Furthermore, the calculation code of JCDS is being incorporated into the PHITS system as a Monte-Carlo transport code. By employing the PHITS system in the dose evaluation, total doses given to a patient by combined modality therapy such as BNCT and X-ray therapy can be estimated accurately. Here, an outline and the performances of the latest version of JCDS are presented, and a future system integrated with JCDS is introduced.

  3. Development of a new neutron monitor using a boron-loaded organic liquid scintillation detector

    CERN Document Server

    Rasolonjatovo, A H D; Kim, E; Nakamura, T; Nunomiya, T; Endo, A; Yamaguchi, Y; Yoshizawa, M

    2002-01-01

    A new type of neutron dose monitor was developed by using a 12.7 cm diameterx12.7 cm long boron-loaded organic liquid scintillation detector BC523A. This detector aims to have a response in the wide energy range of thermal energy to 100 MeV by using the H and C reactions to the fast neutrons of organic liquid and the sup 1 sup 0 B(n, alpha) reaction to thermalized neutrons in the liquid. The response functions of this detector were determined by the Monte Carlo simulation in the energy region from thermal energy to 100 MeV. Using these response functions, the spectrum-weighted dose function, G-function, to get the neutron dose from the light output spectrum of the detector was also determined by the unfolding technique. The calculated G-function was applied to determine the neutron dose in real neutron fields having energies ranging from thermal energy to several tens of MeV, where the light output spectra were measured with the BC523A detector. The thus-obtained ambient doses and effective doses show rather ...

  4. Development of a new neutron monitor using a boron-loaded organic liquid scintillation detector

    Energy Technology Data Exchange (ETDEWEB)

    Rasolonjatovo, A.H.D.; Shiomi, T.; Kim, E.; Nakamura, T. E-mail: nakamura@cyric.tohoku.ac.jp; Nunomiya, T.; Endo, A.; Yamaguchi, Y.; Yoshizawa, M

    2002-10-21

    A new type of neutron dose monitor was developed by using a 12.7 cm diameterx12.7 cm long boron-loaded organic liquid scintillation detector BC523A. This detector aims to have a response in the wide energy range of thermal energy to 100 MeV by using the H and C reactions to the fast neutrons of organic liquid and the {sup 10}B(n, {alpha}) reaction to thermalized neutrons in the liquid. The response functions of this detector were determined by the Monte Carlo simulation in the energy region from thermal energy to 100 MeV. Using these response functions, the spectrum-weighted dose function, G-function, to get the neutron dose from the light output spectrum of the detector was also determined by the unfolding technique. The calculated G-function was applied to determine the neutron dose in real neutron fields having energies ranging from thermal energy to several tens of MeV, where the light output spectra were measured with the BC523A detector. The thus-obtained ambient doses and effective doses show rather good agreement with the fluence-to-dose conversion factor given by ICRP 74. This detector will be useful as a wide-energy range neutron monitor.

  5. Development of the JAERI computational dosimetry system (JCDS) for boron neutron capture therapy. Cooperative research

    CERN Document Server

    Kumada, H; Matsumura, A; Nakagawa, Y; Nose, T; Torii, Y; Uchiyama, J; Yamamoto, K; Yamamoto, T

    2003-01-01

    The Neutron Beam Facility at JRR-4 enables us to carry out boron neutron capture therapy with epithermal neutron beam. In order to make treatment plans for performing the epithermal neutron beam BNCT, it is necessary to estimate radiation doses in a patient's head in advance. The JAERI Computational Dosimetry System (JCDS), which can estimate distributions of radiation doses in a patient's head by simulating in order to support the treatment planning for epithermal neutron beam BNCT, was developed. JCDS is a software that creates a 3-dimentional head model of a patient by using CT and MRI images, and that generates a input data file automatically for calculation of neutron flux and gamma-ray dose distributions in the brain with the Monte Carlo code MCNP, and that displays these dose distributions on the head model for dosimetry by using the MCNP calculation results. JCDS has any advantages as follows; By using CT data and MRI data which are medical images, a detail three-dimensional model of patient's head is...

  6. Potential Effect of Liposomes and Liposome-Encapsulated Botulinum Toxin and Tacrolimus in the Treatment of Bladder Dysfunction.

    Science.gov (United States)

    Janicki, Joseph J; Chancellor, Michael B; Kaufman, Jonathan; Gruber, Michele A; Chancellor, David D

    2016-03-18

    Bladder drug delivery via catheter instillation is a widely used treatment for recurrence of superficial bladder cancer. Intravesical instillation of liposomal botulinum toxin has recently shown promise in the treatment of overactive bladder and interstitial cystitis/bladder pain syndrome, and studies of liposomal tacrolimus instillations show promise in the treatment of hemorrhagic cystitis. Liposomes are lipid vesicles composed of phospholipid bilayers surrounding an aqueous core that can encapsulate hydrophilic and hydrophobic drug molecules to be delivered to cells via endocytosis. This review will present new developments on instillations of liposomes and liposome-encapsulated drugs into the urinary bladder for treating lower urinary tract dysfunction.

  7. Calorimetric study on pH-responsive block copolymer grafted lipid bilayers: rational design and development of liposomes.

    Science.gov (United States)

    Pippa, Natassa; Chountoulesi, Maria; Kyrili, Aimilia; Meristoudi, Anastasia; Pispas, Stergios; Demetzos, Costas

    2016-09-01

    This study is focused on chimeric advanced drug delivery nanosystems and specifically on pH-sensitive liposomes, combining lipids and pH-responsive amphiphilic block copolymers. Chimeric liposomes composed of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and two different forms of block copolymers, i.e. poly(n-butylacrylate)-b-poly(acrylic acid) (PnBA-b-PAA) at 70 and 85% content of PAA at six different molar ratios, each form respectively. PAA block exhibits pH-responsiveness, because of the regulative group of -COOH. -COOH is protonated under acidic pH (pKa ca. 4.2), while remains ionized under basic or neutral pH, leading to liposomes repulse and eventually stability. Lipid bilayers were prepared composed of DPPC and PnBA-b-PAA. Experiments were carried out using differential scanning calorimetry (DSC) in order to investigate their thermotropic properties. DSC indicated disappearance of pre-transition at all chimeric lipid bilayers and slight thermotropic changes of the main transition temperature. Chimeric liposomes have been prepared and their physicochemical characteristics have been explored by measuring the size, size distribution and ζ-potential, owned to the presence of pH-responsive polymer. At percentages containing medium to high amounts of the polymer, chimeric liposomes were found to retain their size during the stability studies. These results were well correlated with those indicated in the DSC measurements of lipid bilayers incorporating polymers in order to explain their physicochemical behavior. The incorporation of the appropriate amount of these novel pH-responsive block copolymers affects thus the cooperativity, the liposomal stabilization and imparts pH-responsiveness.

  8. Application and Development of Liposome Formulation in Pulmonary Delivery%脂质体肺部给药的应用进展

    Institute of Scientific and Technical Information of China (English)

    汪燕; 汤玥; 鲁锡峰; 朱家壁

    2011-01-01

    The liposome-mediated pulmonary drug delivery as a non-invasive administration, makes drugs located at the site of action to treat pulmonary diseases directly, reduces extrapulmonary side-effects,avoids the hepatic first pass effect, increases the bioavailability and avoids frequent administration as the double-layer of the liposome can increase the retention-time. The related advantage of the liposome-mediated pulmonary drug delivery and the way of administration are mainly introduced in this review. We also summarized the research and development of the relevant liposomes at home and abroad, being used to work through pulmonary pathway, as the carriers of antiinflammatory and anti-infective drugs,antioxidants, antasthmatics, antitumor drugs, antithrombotics and so on.%脂质体肺部给药作为一种非侵入性给药形式,可以使药物局部定量化,实现肺部疾病的直接靶向,免除肝脏首过效应,生物利用度高,同时通过脂质双层的延时作用,避免频繁给药.本文介绍了脂质体肺部给药的相关优越性、给药方式以及国内外有关脂质体作为抗炎抗感染药物、抗氧化药物、抗哮喘药物、抗肿瘤药物、抗血栓药物等的载体,通过肺部给药的形式发挥相关作用的研究与进展.

  9. Development of a bone-targeted pH-sensitive liposomal formulation containing doxorubicin: physicochemical characterization, cytotoxicity, and biodistribution evaluation in a mouse model of bone metastasis

    Science.gov (United States)

    Ferreira, Diêgo dos Santos; Faria, Samilla Dornelas; Lopes, Sávia Caldeira de Araújo; Teixeira, Cláudia Salviano; Malachias, Angelo; Magalhães-Paniago, Rogério; de Souza Filho, José Dias; Oliveira, Bruno Luis de Jesus Pinto; Guimarães, Alexander Ramos; Caravan, Peter; Ferreira, Lucas Antônio Miranda; Alves, Ricardo José; Oliveira, Mônica Cristina

    2016-01-01

    Background Despite recent advances in cancer therapy, the treatment of bone tumors remains a major challenge. A possible underlying hypothesis, limitation, and unmet need may be the inability of therapeutics to penetrate into dense bone mineral, which can lead to poor efficacy and high toxicity, due to drug uptake in healthy organs. The development of nanostructured formulations with high affinity for bone could be an interesting approach to overcome these challenges. Purpose To develop a liposomal formulation with high affinity for hydroxyapatite and the ability to release doxorubicin (DOX) in an acidic environment for future application as a tool for treatment of bone metastases. Materials and methods Liposomes were prepared by thin-film lipid hydration, followed by extrusion and the sulfate gradient-encapsulation method. Liposomes were characterized by average diameter, ζ-potential, encapsulation percentage, X-ray diffraction, and differential scanning calorimetry. Release studies in buffer (pH 7.4 or 5), plasma, and serum, as well as hydroxyapatite-affinity in vitro analysis were performed. Cytotoxicity was evaluated by MTT assay against the MDA-MB-231 cell line, and biodistribution was assessed in bone metastasis-bearing animals. Results Liposomes presented suitable diameter (~170 nm), DOX encapsulation (~2 mg/mL), controlled release, and good plasma and serum stability. The existence of interactions between DOX and the lipid bilayer was proved through differential scanning calorimetry and small-angle X-ray scattering. DOX release was faster when the pH was in the range of a tumor than at physiological pH. The bone-targeted formulation showed a strong affinity for hydroxyapatite. The encapsulation of DOX did not interfere in its intrinsic cytotoxicity against the MDA-MB-231 cell line. Biodistribution studies demonstrated high affinity of this formulation for tumors and reduction of uptake in the heart. Conclusion These results suggest that bone-targeted p

  10. Development of the JAERI computational dosimetry system (JCDS) for boron neutron capture therapy. Cooperative research

    Energy Technology Data Exchange (ETDEWEB)

    Kumada, Hiroaki; Yamamoto, Kazuyoshi; Torii, Yoshiya; Uchiyama, Junzo [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment; Matsumura, Akira; Yamamoto, Tetsuya; Nose, Tadao [Tsukuba Univ., Tsukuba, Ibaraki (Japan); Nakagawa, Yoshinobu [National Sanatorium Kagawa-Children' s Hospital, Kagawa (Japan); Kageji, Teruyoshi [Tokushima Univ., Tokushima (Japan)

    2003-03-01

    The Neutron Beam Facility at JRR-4 enables us to carry out boron neutron capture therapy with epithermal neutron beam. In order to make treatment plans for performing the epithermal neutron beam BNCT, it is necessary to estimate radiation doses in a patient's head in advance. The JAERI Computational Dosimetry System (JCDS), which can estimate distributions of radiation doses in a patient's head by simulating in order to support the treatment planning for epithermal neutron beam BNCT, was developed. JCDS is a software that creates a 3-dimentional head model of a patient by using CT and MRI images, and that generates a input data file automatically for calculation of neutron flux and gamma-ray dose distributions in the brain with the Monte Carlo code MCNP, and that displays these dose distributions on the head model for dosimetry by using the MCNP calculation results. JCDS has any advantages as follows; By using CT data and MRI data which are medical images, a detail three-dimensional model of patient's head is able to be made easily. The three-dimensional head image is editable to simulate the state of a head after its surgical processes such as skin flap opening and bone removal in the BNCT with craniotomy that are being performed in Japan. JCDS can provide information for the Patient Setting System which can support to set the patient to an actual irradiation position swiftly and accurately. This report describes basic design of JCDS and functions in several processing, calculation methods, characteristics and performance of JCDS. (author)

  11. Liposome imaging agents in personalized medicine

    DEFF Research Database (Denmark)

    Petersen, Anncatrine Luisa; Hansen, Anders Elias; Gabizon, Alberto;

    2012-01-01

    that selectively localize in tumor tissue can transport both drugs and imaging agents, which allows for a theranostic approach with great potential in personalized medicine. Radiolabeling of liposomes have for many years been used in preclinical studies for evaluating liposome in vivo performance and has been...... start to consider how to use imaging for patient selection and treatment monitoring in connection to nanocarrier based medicines. Nanocarrier imaging agents could furthermore have interesting properties for disease diagnostics and staging. Here, we review the major advances in the development...... of radiolabeled liposomes for imaging as a tool in personalized medicine....

  12. Effect Anticipation of Boron on Seawater Reverse Osmosis Desalination Development%硼对反渗透海水淡化发展的影响预期

    Institute of Scientific and Technical Information of China (English)

    葛云红; 冯厚军

    2011-01-01

    Comparing to the need for economic and social development, water resources are severely deficient, which leads to fast development of seawater desalination at home and abroad. Desalination plants tend to large scale, and the use extends from industrial to municipal water supply. Many people suspect the security of desalinated seawater as drinking water, and boron is a problem which draws people' s attention. The present forms of boron in seawater, boron level in desalinated seawater by different seawater desalination methods, boron removal methods and influencing factors are summarized. The boron removal situation in international large-scale seawater reverse osmosis desalination projects, effects of boron on human health and crop, drinking water quality guidelines for boron at home and abroad and their developing trend are introduced.%水资源量与经济社会发展需求相比严重不足,使得海水淡化迅速发展起来,规模呈大型化发展趋势,用途也逐渐从工业向市政供水扩展.很多人对海水淡化水作为饮用水的安全性存在疑虑,其中硼是人们一直比较关注的问题.概括了硼在海水中的存在形式、不同海水淡化方法产水的硼含量、脱硼方法及影响因素分析,同时介绍了国外大型反渗透海水淡化工程的脱硼情况、硼对人体健康的影响和对农作物的影响,以及国内外饮用水水质标准对硼含量的规定和发展趋势.

  13. Paramagnetic Liposome Nanoparticles for Cellular and Tumour Imaging

    Directory of Open Access Journals (Sweden)

    Nazila Kamaly

    2010-04-01

    Full Text Available In this review we discuss the development of paramagnetic liposomes incorporating MRI contrast agents and show how these are utilized in cellular imaging in vitro. Bi-functional, bi-modal imaging paramagnetic liposome systems are also described. Next we discuss the upgrading of paramagnetic liposomes into bi-modal imaging neutral nanoparticles for in vivo imaging applications. We discuss the development of such systems and show how paramagnetic liposomes and imaging nanoparticles could be developed as platforms for future multi-functional, multi-modal imaging theranostic nanodevices tailor-made for the combined imaging of early stage disease pathology and functional drug delivery.

  14. EFFECTS OF SILVER NANOPARTICLES IN SOLUTION AND LIPOSOMAL FORM ON SOME BLOOD PARAMETERS IN FEMALE RABBITS DURING FERTILIZATION AND EARLY EMBRYONIC DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    Vasyl Syrvatka

    2014-02-01

    Full Text Available Silver nanoparticles are the most rapidly growing classes of nanoproducts. In this study, we investigated the influence of subcutaneous injections of silver nanoparticles in solution and in liposomal form on hematological and biochemical parameters of blood of New Zealand White rabbits during hormonal treatment, fertilization and early embryonic development. The females treated by free silver nanoparticles and silver nanoparticles in liposomal form received silver at a dose of 10 µg/kg/day in 5 % glucose solution during 28 days. Blood sampling was done four times: the day before the compounds administration; on day 7 after the compounds administration; in the period after hormonal induction and fertilization and on the 14th day of pregnancy. Our results showed changes in some biochemical (lactate dehydrogenase activities, progesterone and estradiol concentration, malondialdehyde level, etc. and hematological (hematocrit, mean cell volume, mean corpuscular hemoglobin concentration, etc. parameters under the influence of hormonal treatment and pregnancy. The concentration of progesterone showed significantly higher values (P˂0.05 on GDs 1 in S group than in C group. The percentage of neutrophils was significantly higher in SG rabbits after 7 days of silver nanoparticles administration than that in the CG. There were no significant changes in red blood cells parameters, platelets, and activity of some ferments (ALP, AST, ALT, LDH, GGT between control and silver groups during the entire period of experiment. In conclusion, the hematological and biochemical values of blood obtained in the given study showed that free silver nanoparticles and silver nanoparticles in liposomal form in the investigated concentrations had no toxic effect on hormonal treatment, fertilization and early embryonic development in New Zealand White rabbits.

  15. New drug candidates for liposomal delivery identified by computer modeling of liposomes' remote loading and leakage.

    Science.gov (United States)

    Cern, Ahuva; Marcus, David; Tropsha, Alexander; Barenholz, Yechezkel; Goldblum, Amiram

    2017-02-16

    Remote drug loading into nano-liposomes is in most cases the best method for achieving high concentrations of active pharmaceutical ingredients (API) per nano-liposome that enable therapeutically viable API-loaded nano-liposomes, referred to as nano-drugs. This approach also enables controlled drug release. Recently, we constructed computational models to identify APIs that can achieve the desired high concentrations in nano-liposomes by remote loading. While those previous models included a broad spectrum of experimental conditions and dealt only with loading, here we reduced the scope to the molecular characteristics alone. We model and predict API suitability for nano-liposomal delivery by fixing the main experimental conditions: liposome lipid composition and size to be similar to those of Doxil® liposomes. On that basis, we add a prediction of drug leakage from the nano-liposomes during storage. The latter is critical for having pharmaceutically viable nano-drugs. The "load and leak" models were used to screen two large molecular databases in search of candidate APIs for delivery by nano-liposomes. The distribution of positive instances in both loading and leakage models was similar in the two databases screened. The screening process identified 667 molecules that were positives by both loading and leakage models (i.e., both high-loading and stable). Among them, 318 molecules received a high score in both properties and of these, 67 are FDA-approved drugs. This group of molecules, having diverse pharmacological activities, may be the basis for future liposomal drug development.

  16. Progress involving new techniques for liposome preparation

    Directory of Open Access Journals (Sweden)

    Zhenjun Huang

    2014-08-01

    Full Text Available The article presents a review of new techniques being used for the preparation of liposomes. A total of 28 publications were examined. In addition to the theories, characteristics and problems associated with traditional methods, the advantages and drawbacks of the latest techniques were reviewed. In the light of developments in many relevant areas, a variety of new techniques are being used for liposome preparation and each of these new technique has particular advantages over conventional preparation methods. However, there are still some problems associated with these new techniques that could hinder their applications and further improvements are needed. Generally speaking, due to the introduction of these latest techniques, liposome preparation is now an improved procedure. These applications promote not only advances in liposome research but also the methods for their production on an industrial scale.

  17. Heterogeneous PNA Liposomes for Gene Delivery

    Science.gov (United States)

    Marques, Bruno; Morfesis, Ana; Yoon, Diana; Schneider, James

    2002-03-01

    To circumvent complications of DNA adsorption onto cationic liposomes (i.e. structural reorganization, cytotoxicity), we have developed a liposomal system that binds genetic material via hydrogen bonding interactions. These liposomes contain surfactants linked to peptide nucleic acid (PNA), a synthetic DNA mimic with unique DNA-binding properties. We target multiple short regions of the DNA strand, sequestering the DNA from nuclease in solution, to protect it from nuclease digestion. Here, we present zeta potential measurements quantifying the extent of PNA incorporation in the liposomes, as well as the extent of DNA binding and nuclease activity under various conditions for mixtures of di- and trinucleotide PNA. We also discuss our attempts to identify the minimal PNA oligomer length to achieve stable binding and sequence specificity.

  18. Predicting the influence of liposomal lipid composition on liposome size, zeta potential and liposome-induced dendritic cell maturation using a design of experiments approach.

    Science.gov (United States)

    Soema, Peter C; Willems, Geert-Jan; Jiskoot, Wim; Amorij, Jean-Pierre; Kersten, Gideon F

    2015-08-01

    In this study, the effect of liposomal lipid composition on the physicochemical characteristics and adjuvanticity of liposomes was investigated. Using a design of experiments (DoE) approach, peptide-containing liposomes containing various lipids (EPC, DOPE, DOTAP and DC-Chol) and peptide concentrations were formulated. Liposome size and zeta potential were determined for each formulation. Moreover, the adjuvanticity of the liposomes was assessed in an in vitro dendritic cell (DC) model, by quantifying the expression of DC maturation markers CD40, CD80, CD83 and CD86. The acquired data of these liposome characteristics were successfully fitted with regression models, and response contour plots were generated for each response factor. These models were applied to predict a lipid composition that resulted in a liposome with a target zeta potential. Subsequently, the expression of the DC maturation factors for this lipid composition was predicted and tested in vitro; the acquired maturation responses corresponded well with the predicted ones. These results show that a DoE approach can be used to screen various lipids and lipid compositions, and to predict their impact on liposome size, charge and adjuvanticity. Using such an approach may accelerate the formulation development of liposomal vaccine adjuvants.

  19. Plasmon resonant liposomes for controlled drug delivery

    Science.gov (United States)

    Knights-Mitchell, Shellie S.; Romanowski, Marek

    2015-03-01

    Nanotechnology use in drug delivery promotes a reduction in systemic toxicity, improved pharmacokinetics, and better drug bioavailability. Liposomes continue to be extensively researched as drug delivery systems (DDS) with formulations such as Doxil® and Ambisome® approved by FDA and successfully marketed in the United States. However, the limited ability to precisely control release of active ingredients from these vesicles continues to challenge the broad implementation of this technology. Moreover, the full potential of the carrier to sequester drugs until it can reach its intended target has yet to be realized. Here, we describe a liposomal DDS that releases therapeutic doses of an anticancer drug in response to external stimulus. Earlier, we introduced degradable plasmon resonant liposomes. These constructs, obtained by reducing gold on the liposome surface, facilitate spatial and temporal release of drugs upon laser light illumination that ultimately induces an increase in temperature. In this work, plasmon resonant liposomes have been developed to stably encapsulate and retain doxorubicin at physiological conditions represented by isotonic saline at 37o C and pH 7.4. Subsequently, they are stimulated to release contents either by a 5o C increase in temperature or by laser illumination (760 nm and 88 mW/cm2 power density). Successful development of degradable plasmon resonant liposomes responsive to near-infrared light or moderate hyperthermia can provide a new delivery method for multiple lipophilic and hydrophilic drugs with pharmacokinetic profiles that limit clinical utility.

  20. Materials Development for Boron Phosphide Based Neutron Detectors: Final Technical Report

    Energy Technology Data Exchange (ETDEWEB)

    Edgar, James Howard [Kansas State Univ., Manhattan, KS (United States)

    2014-09-09

    The project goal was to improve the quality of boron phosphide (BP) by optimizing its epitaxial growth on single crystal substrates and by producing bulk BP single crystals with low dislocation densities. BP is potentially a good semiconductor for high efficiency solid state neutron detectors by combining neutron capture and charge creation within the same volume. The project strategy was to use newly available single crystal substrates, silicon carbide and aluminum nitride, engineered to produce the best film properties. Substrate variables included the SiC polytype, crystallographic planes, misorientation of the substrate surface (tilt direction and magnitude) from the major crystallographic plane, and surface polarity (Si and C). The best films were (111)BP on silicon-face (0001) 4H-SiC misoriented 4° in the [1-100] direction, and BP on (100) and (111) 3C-SiC/Si; these substrates resulted in films that were free of in-plane twin defects, as determined by x-ray topography. The impact of the deposition temperature was also assessed: increasing the temperature from 1000 °C to 1200 °C produced films that were more ordered and more uniform, and the size of individual grains increased by more than a factor of twenty. The BP films were free of other compounds such as icosahedral boron phosphide (B12P2) over the entire temperature range, as established by Raman spectroscopy. The roughness of the BP films was reduced by increasing the phosphine to diborane ratio from 50 to 200. Bulk crystals were grown by reacting boron dissolved in nickel with phosphorus vapor to precipitate BP. Crystals with dimensions up to 2 mm were produced.

  1. In vitro characteristics of liposomes and double liposomes prepared using a novel glass beads method.

    Science.gov (United States)

    Yamabe, Kenji; Kato, Yoshinori; Onishi, Hiraku; Machida, Yoshiharu

    2003-06-01

    A novel preparative method for liposomes and double liposomes (DL) using glass beads was superior to a glass-filter method developed previously. Lipid dissolved in chloroform was poured into a kjeldahl flask with glass beads (BZ-04, 0.350-0.500 mm phi; BZ-3, 2.794-3.962 mm phi; or BZ-6, 5.613-6.680 mm phi), and the organic solvent was evaporated. The lipid layer that formed on the glass beads was hydrated with 1.5 ml of the suspension of inner liposomes at a temperature above the phase transition temperature of the lipids employed, and was agitated vigorously. Erythrosine (ER) was used as a model drug. The size of liposomes prepared by the glass beads method depended on the size of the glass beads. The size of the liposomes became smaller as glass beads with a smaller size were used. A high encapsulation efficiency was observed when glass bead blends consisting of two different sizes were used. Large sizes (BZ-3/BZ-6) had a tendency to show high encapsulation efficiency and size also played an important role in the formation of liposomes. DL formation inhibited the release of ER and DL formative efficiency was markedly improved by means of the glass beads method. These findings suggested that the glass beads method developed in this study conferred a high drug loading and a high DL formation on liposomes compared with ordinary methods.

  2. Liposomal delivery of radionuclides for cancer diagnostics and radiotherapy

    DEFF Research Database (Denmark)

    Petersen, Anncatrine Luisa

    , as the use of positron emission tomography (PET) scanners for molecular and diagnostic imaging has become more attractive. Furthermore, the importance of molecular and diagnostic imaging in nanotechnology has also been recognized, and significant research has been conducted on radiolabeled liposomes...... for scintigraphy and single photon emission computed tomography (SPECT) imaging. Preclinical as well as clinical SPECT studies on radiolabeled liposomes have contributed with valuable information on the pharmacokinetics of liposomes during several liposomal drug developments. SPECT has lower detection sensitivity......, an in vivo study is presented, where passive tumor accumulation of 64Cu loaded liposomes (64Cu-liposomes) in tumor-bearing mice was quantified directly by PET and computed tomography (CT) imaging. Furthermore, Article I present an evaluation and quantitative measurement of the biodistribution of 64Cu...

  3. Liposomal amphotericin B for the treatment of visceral leishmaniasis.

    Science.gov (United States)

    Bern, Caryn; Adler-Moore, Jill; Berenguer, Juan; Boelaert, Marleen; den Boer, Margriet; Davidson, Robert N; Figueras, Concepcion; Gradoni, Luigi; Kafetzis, Dimitris A; Ritmeijer, Koert; Rosenthal, Eric; Royce, Catherine; Russo, Rosario; Sundar, Shyam; Alvar, Jorge

    2006-10-01

    During the past decade, liposomal amphotericin B has been used with increasing frequency to treat visceral leishmaniasis (VL). The World Health Organization convened a workshop to review current knowledge and to develop guidelines for liposomal amphotericin B use for VL. In Europe, liposomal amphotericin B is widely used to treat VL. In Africa and Asia, the VL disease burden is high and drug access is poor; liposomal amphotericin B is available only through preferential pricing for nonprofit groups in East Africa. Clinical trials and experience demonstrate high efficacy and low toxicity for liposomal amphotericin B (total dose, 20 mg/kg) in immunocompetent patients with VL. Combination trials in areas with antileishmanial drug resistance, and treatment and secondary prophylaxis trials in VL-human immunodeficiency virus-coinfected patients, are important to safeguard the current armamentarium and to optimize regimens. The public health community should work to broaden access to preferential liposomal amphotericin B pricing by public sector VL treatment programs.

  4. Liposome Delivery Systems for Inhalation: A Critical Review Highlighting Formulation Issues and Anticancer Applications.

    Science.gov (United States)

    Rudokas, Mindaugas; Najlah, Mohammad; Alhnan, Mohamed Albed; Elhissi, Abdelbary

    2016-01-01

    This is a critical review on research conducted in the field of pulmonary delivery of liposomes. Issues relating to the mechanism of nebulisation and liposome composition were appraised and correlated with literature reports of liposome formulations used in clinical trials to understand the role of liposome size and composition on therapeutic outcome. A major highlight was liposome inhalation for the treatment of lung cancers. Many in vivo studies that explored the potential of liposomes as anticancer carrier systems were evaluated, including animal studies and clinical trials. Liposomes can entrap anticancer drugs and localise their action in the lung following pulmonary delivery. The safety of inhaled liposomes incorporating anticancer drugs depends on the anticancer agent used and the amount of drug delivered to the target cancer in the lung. The difficulty of efficient targeting of liposomal anticancer aerosols to the cancerous tissues within the lung may result in low doses reaching the target site. Overall, following the success of liposomes as inhalable carriers in the treatment of lung infections, it is expected that more focus from research and development will be given to designing inhalable liposome carriers for the treatment of other lung diseases, including pulmonary cancers. The successful development of anticancer liposomes for inhalation may depend on the future development of effective aerosolisation devices and better targeted liposomes to maximise the benefit of therapy and reduce the potential for local and systemic adverse effects.

  5. Liposomal amphotericin B: clinical experience and perspectives.

    Science.gov (United States)

    Gibbs, Winter J; Drew, Richard H; Perfect, John R

    2005-04-01

    While amphotericin B deoxycholate (Fungizone, Apothecon Pharmaceuticals) has been considered by many to be the gold standard for the treatment for numerous invasive fungal infections for over 45 years, toxicities associated with its use often necessitate treatment modification or discontinuation. Lipid-based formulations, including liposomal amphotericin B (AmBisome, Fujisawa Healthcare, Inc.), were developed to decrease many of these toxicities while retaining broad antifungal spectrum and potency of amphotericin B. In clinical trials, liposomal amphotericin B has demonstrated efficacy comparable to that of amphotericin B deoxycholate while reducing the incidence of treatment-related nephrotoxicity, electrolyte-wasting, and infusion-related reactions. In addition, recent clinical trials have also compared liposomal amphotericin B with other antifungal classes. Acquisition costs of liposomal amphotericin B are substantially higher than those of amphotericin B deoxycholate and other antifungals. While pharmacoeconomic analyses consider outcomes and other treatment-related costs, they have yet to clearly demonstrate the cost-effectiveness of liposomal amphotericin B when compared with amphotericin B deoxycholate or other antifungal agents. This review will focus primarily on recent liposomal amphotericin B experience and attempt to put its use into perspective considering other available antifungal agents.

  6. Development of a bone-targeted pH-sensitive liposomal formulation containing doxorubicin: physicochemical characterization, cytotoxicity, and biodistribution evaluation in a mouse model of bone metastasis

    Directory of Open Access Journals (Sweden)

    Ferreira DS

    2016-08-01

    Full Text Available Diêgo dos Santos Ferreira,1,2 Samilla Dornelas Faria,1 Sávia Caldeira de Araújo Lopes,1 Cláudia Salviano Teixeira,1 Angelo Malachias,3 Rogério Magalhães-Paniago,3 José Dias de Souza Filho,4 Bruno Luis de Jesus Pinto Oliveira,2 Alexander Ramos Guimarães,2 Peter Caravan,2 Lucas Antônio Miranda Ferreira,1 Ricardo José Alves,1 Mônica Cristina Oliveira1 1Department of Pharmaceutical Products, Faculty of Pharmacy,Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; 2Athinoula A Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; 3Department of Physics, 4Department of Chemistry, Institute of Exact Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil Background: Despite recent advances in cancer therapy, the treatment of bone tumors remains a major challenge. A possible underlying hypothesis, limitation, and unmet need may be the inability of therapeutics to penetrate into dense bone mineral, which can lead to poor efficacy and high toxicity, due to drug uptake in healthy organs. The development of nanostructured formulations with high affinity for bone could be an interesting approach to overcome these challenges.Purpose: To develop a liposomal formulation with high affinity for hydroxyapatite and the ability to release doxorubicin (DOX in an acidic environment for future application as a tool for treatment of bone metastases.Materials and methods: Liposomes were prepared by thin-film lipid hydration, followed by extrusion and the sulfate gradient-encapsulation method. Liposomes were characterized by average diameter, ζ-potential, encapsulation percentage, X-ray diffraction, and differential scanning calorimetry. Release studies in buffer (pH 7.4 or 5, plasma, and serum, as well as hydroxyapatite-affinity in vitro analysis were performed. Cytotoxicity was evaluated by MTT assay against the MDA-MB-231 cell line, and biodistribution was

  7. Liposomal formulations of amphotericin B: differences according to the scientific evidence.

    Science.gov (United States)

    Azanza, José Ramón; Sádada, Belén; Reis, Joana

    2015-12-01

    This article presents an overview of the characteristics of liposomes as drug carriers, particularly in relation to liposomal formulations of amphotericin B. General features regarding structure, liposome-cell interactions, stability, encapsulation of active substances and elimination of liposomes are described. Up to the present time extensive efforts to produce similar or bioequivalent products of amphotericin B formulations, in particular in the case of liposomal amphotericin B, have been unsuccessful in spite of having a very similar composition and even an apparently identical manufacturing process. Guidelines for the development of generic liposomal formulations developed by the FDA and EMA are also summarized. Based on the available evidence of the composition of liposomes, any differences in the manufacturing process even if the same lipid composition is used may result in different final products. Therefore, it seems unreasonable to infer that all amphotericin B liposomal formulations are equal in efficacy and safety.

  8. Development of a novel microbubble-liposome complex conjugated with peptide ligands targeting IL4R on brain tumor cells.

    Science.gov (United States)

    Park, See-Hyoung; Yoon, Young Ii; Moon, Hyoungwon; Lee, Ga-Hyun; Lee, Byung-Heon; Yoon, Tae-Jong; Lee, Hak Jong

    2016-07-01

    Gas (SF6)-filled microbubbles (MBs) were prepared by emulsion and solvent-evaporation method. The prepared MBs were further conjugated with doxorubicin (Dox)-loaded nano-sized liposome and peptide ligands to interleukin-4 receptor (IL4R) for targeting brain tumor cells. The final MB-liposome (Dox)-IL4R targeting peptide ligand [MB-Lipo (Dox)-IL4RTP] had a spherical structure with the mean size of 1,500 nm. The MB-Lipo (Dox)‑IL4RTP exhibited cellular uptake in U87MG brain tumor cells (a brain tumor cell line expressing strongly IL4R) with frequency ultrasound energy suggesting that MB-Lipo (Dox)‑IL4RTP provided effective targeting ability for brain tumor cells. In addition, WST-1 assay results showed that MB-Lipo (Dox)‑IL4RTP inhibited the proliferation of U87MG cells IL4R‑dependently. This was confirmed by western blotting of γH2AX, phospho (Ser15)-p53, p53 and p21 which are signal transduction proteins involved in DNA damage response and cell cycle arrest. Taken together, these results indicate that MB-Lipo (Dox)-IL4RTP represents a promising ultrasonic contrast agent for tumor-targeting ultrasonic imaging.

  9. Development and validation of a single collector ICPMS procedure to determine boron isotopeic compositions of water and food samples

    Science.gov (United States)

    Vogl, Jochen; Rosner, Martin; Pritzkow, Wolfgang

    2010-05-01

    Authenticity and provenance studies as well as issues in environmental- and geo-sciences are hot topics in nowadays isotope research. Elements being known for their natural isotopic variation, such as lead and strontium, are being used to assign the provenance of artefacts, food and other products. A recent study revealed the potential of boron (B) isotopes for delivering information on the provenance of crop plants. To offer alternative analytical instrumentations beside the classical TIMS procedures a single collector ICPMS procedure for B isotope analyses has been developed and validated. This procedure should enable more B isotope studies, as single collector ICPMS intruments are more widepread in the relevant laboratories compared to TIMS. The developed procedures for the determination of B isotopic compositions use a magnetic sector ICPMS and consist of one low resolution (LR) and one medium resolution (MR) procedure. The absolute standard deviation for the δ11B determination in three independently measured samples lies between 0.2 and 0.8 ‰ for the LR and between 0.3 and 1.5 ‰ for the MR. The expanded uncertainties with a coverage factor of k=2 range between 1.4 and 1.6 ‰ for the LR and between 2.9 and 3.2 ‰ for the MR. The trueness, expressed as average deviation from the reference values, is less than 1.1 ‰ for LR and 0.8 ‰ for MR. To test the practicability of the procedure the matrix tolerance has been investigated. Using a measurement solution containing 100 µg/kg boron a matrix of 2 mg/kg of alkaline and earth alkaline elements was found as a limit for stable instrumental mass discrimination. Thus a highly efficient matrix separation is required, similar to TIMS. The developed procedure is well suited for the for B isotope studies of various matrices and especially the LR procedure offers relatively small uncertainties combined with high sample throughput.

  10. Design, development and characterization of multi-functionalized gold nanoparticles for biodetection and targeted boron delivery in BNCT applications.

    NARCIS (Netherlands)

    Mandal, S.; Bakeine, G.J.; Krol, S.; Ferrari, C.; Clerici, A.M.; Zonta, C.; Cansolino, L.; Ballarini, F.; Bortolussi, S.; Stella, S.; Protti, N.; Bruschi, P.; Altieri, S.

    2011-01-01

    The aim of this study is to optimize targeted boron delivery to cancer cells and its tracking down to the cellular level. To this end, we describe the design and synthesis of novel nanovectors that double as targeted boron delivery agents and fluorescent imaging probes. Gold nanoparticles were coate

  11. 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

    1997-01-01

    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

  12. Liposomal formulations of cytotoxic drugs.

    Science.gov (United States)

    Janknegt, R

    1996-07-01

    Liposomes are microscopic particles of lipid bilayer membrane that enclose aqueous internal compartments. These drug-delivery systems offer a very interesting opportunity for delivering cytotoxic drugs with equal or improved clinical efficacy and reduced toxicity. The most important clinical application of liposomes until now has been the inclusion of amphotericin B. At the same dose level, liposomal amphotericin B is as effective or slightly less effective than the conventional formulation, but much higher dosages, up to 5-7 mg kg-1day-1, can be given with acceptable toxicity. There are three preparations of cytotoxic drugs in an advanced stage of commercial development. Two of these (Doxil and TLD D99) contain doxorubicin and the other (DaunoXome) contains daunorubicin. The cardiac toxicity of the three preparations under clinical evaluation appears to be low in comparison with conventional doxorubicin or daunorubicin. No direct comparisons between the new formulations are available, so it is not yet possible to make any statements concerning their relative efficacy and toxicity. DaunoXome is the only drug that is approved in any country, and is also the best documented. It is too early to make recommendations concerning the place of these drugs in therapy. The marked increase in concentrations at the site of the tumour has yet to lead to increased therapeutic efficacy. These findings need further investigation. The efficacy of liposomal preparations in Kaposi's sarcoma appears to be similar to that of standard therapy and the clinical tolerance is good. Perhaps combination therapy with other cytotoxic agents could result in improved clinical efficacy. Their cost will probably be high in comparison with standard therapies.

  13. Development of Nano-Liposomal Formulations of Epidermal Growth Factor Receptor Inhibitors and their Pharmacological Interactions on Drug-Sensitive and Drug-Resistant Cancer Cell Lines

    Science.gov (United States)

    Trummer, Brian J.

    A rapidly expanding understanding of molecular derangements in cancer cell function has led to the development of selective, targeted chemotherapeutic agents. Growth factor signal transduction networks are frequently activated in an aberrant fashion, particularly through the activity of receptor tyrosine kinases (RTK). This has spurred an intensive effort to develop receptor tyrosine kinase inhibitors (RTKI) that are targeted to specific receptors, or receptor subfamilies. Chapter 1 reviews the pharmacology, preclinical, and clinical aspects of RTKIs that target the epidermal growth factor receptor (EGFR). EGFR inhibitors demonstrate significant success at inhibiting phosphorylation-based signaling pathways that promote cancer cell proliferation. Additionally RTKIs have physicochemical and structural characteristics that enable them to function as inhibitors of multi-drug resistance transport proteins. Thus EGFR inhibitors and other RTKIs have both on-target and off-target activities that could be beneficial in cancer therapy. However, these agents exert a number of side effects, some of which arise from their hydrophobic nature and large in vivo volume of distribution. Side effects of the EGFR inhibitor gefitinib include skin rash, severe myelotoxicity when combined with certain chemotherapeutic agents, and impairment of the blood brain barrier to xenobiotics. Weighing the preclinical and clinical observations with the EGFR inhibitors, we developed the primary overall hypothesis of this research: that drug-carrier formulations of RTKIs such as the EGFR inhibitors could be developed based on nanoparticulate liposomal carriers. Theoretically, this carrier strategy would ameliorate toxicity and improve the biodistribution and tumor selectivity of these agents. We hypothesized specifically that liposomal formulations could shift the biodistribution of EGFR inhibitors such as gefitinib away from skin, bone marrow, and the blood brain barrier, and toward solid tumors

  14. Enhanced antitumor effect of novel dual-targeted paclitaxel liposomes

    Energy Technology Data Exchange (ETDEWEB)

    Meng Shuyan; Su Bo; Li Wei; Ding Yongmei; Tang Liang; Zhou Wei; Song Yin; Li Heyan; Zhou Caicun, E-mail: caicunzhou@yahoo.com.cn [Cancer Institute of Tongji University School of Medicine, Shanghai Pulmonary Hospital, 507 Zhengmin Road, Shanghai (China)

    2010-10-15

    A novel dual-targeted peptide containing an alpha V integrins specific ligand and a neuropilin-1 specific motif was developed which showed an increased specific targeting affinity to tumors. Active dual-targeted liposomes were then produced with this peptide and exhibited greater binding activity than single-targeted liposomes in vitro. Paclitaxel entrapped in this formulation greatly increased the uptake of paclitaxel in the targeting cells and significantly suppressed the growth of HUVEC and A549 cells compared with general paclitaxel injections (Taxol) and single-targeted paclitaxel liposomes. The treatment of tumor xenograft models with dual-targeted paclitaxel liposomes also resulted in better tumor growth inhibition than any other treatment groups. Therefore, the dual-targeted paclitaxel liposomes prepared in the present study might be a more promising drug for cancer treatment. Furthermore, the dual-targeting approach may produce synergistic effects that can be applied in the development of new targeted drug delivery systems.

  15. [Liposomal amphotericin B].

    Science.gov (United States)

    Fukasawa, Masatomo

    2005-01-01

    Liposomal amphotericin B (AmBisome) is a DDS (drug delivery system) formulation of amphotericin B (AMPH-B), and has been developed in an attempt to reduce the toxicity of AMPH-B while retaining its therapeutic efficacy. AMPH-B has been the "gold standard" of antifungal therapy over the past four decades. It has a broad spectrum of fungicidal activity against a number of clinically important pathogens including Aspergillus and Candida. The mechanism of action of AMPH-B involves binding to ergosterol, the principal sterol in fungal cell membranes. Binding to ergosterol causes an increase in fungal membrane permeability, electrolyte leakage, and cell death. AMPH-B has affinity for cholesterol in mammalian membranes, which leads to severe side-effects including kidney damage. AmBisome is a unilamellar vesicle composed of AMPH-B and phospholipid. Upon administration, AmBisome remains intact in the blood and distributes to the tissues where fungal infection may occur, and is disrupted after attachment to the outside of fungal cells, resulting in fungal cell death. AmBisome and AMPH-B show similar in vitro and in vivo antifungal activity and clinical efficacy. However, AmBisome has less infusion-related toxicity and nephrotoxicity than AMPH-B.

  16. MRI shows clodronate-liposomes attenuating liverinjuryinratswithsevereacutepancreatitis

    Institute of Scientific and Technical Information of China (English)

    Jian-Xin Zhang; Sheng-Chun Dang; Yong Zhang; Xin Sha; Li-Rong Zhang; Chuan-She Wei; Min Chen; De-Li Jiang

    2010-01-01

    BACKGROUND: Studies have revealed that macrophages play an important role in the development of severe acute pancreatitis (SAP). Activated macrophages can lead to a systemic inlfammatory response, induce lipid peroxidation, impair membrane structure, result in injury to the liver and the other extrahepatic organs, and eventually result in multiple organ dysfunction syndrome by promoting excessive secretion of cytokines. Liver injury can further aggravate the systemic inlfammatory response and increase mortality by affecting the metabolism of toxins and the release of excessive inlfammatory mediators. Clodronate is a synthetic bisphosphonate, which is often used for treating bone changes caused by osteoporosis and other factors. In the current study, we created liposomes containing superparamagnetic iron oxide particles (SPIOs) for macrophage labeling and magnetic resonance imaging, using a novel method that can bind the clodronate to induce apoptosis and deplete macrophages. METHODS: Superparamagnetic Fe3O4 nanoparticles were prepared by chemical coprecipitation. SPIO-containing liposomes and SPIO-clodronate-containing liposomes were prepared by the thin iflm method. SAP models were prepared by injection of sodium taurocholate (2 ml/kg body weight) into the subcapsular space of the pancreas. Sprague-Dawley rats were randomly divided into a control group, a SAP plus SPIO-liposome group, and a SAP plus SPIO-clodronate-containing group. Two and six hours after SAP models were available, T2-weighted MRI scans (in the same plane) of the livers of rats in each group were performed. At the end of the scans, 2 ml of blood was taken from the superior mesenteric vein to measure the levels of serum amylase, ALT, AST, TNF-α, and IL-6. Pathological changes in the liver and pancreas were assessed. RESULTS: Transmission electron microscopy showed that the liposomes had a uniform size. No pathological changes in the pancreata of rats in the control group were noted. The

  17. Liposomal drug delivery systems: from concept to clinical applications.

    Science.gov (United States)

    Allen, Theresa M; Cullis, Pieter R

    2013-01-01

    The first closed bilayer phospholipid systems, called liposomes, were described in 1965 and soon were proposed as drug delivery systems. The pioneering work of countless liposome researchers over almost 5 decades led to the development of important technical advances such as remote drug loading, extrusion for homogeneous size, long-circulating (PEGylated) liposomes, triggered release liposomes, liposomes containing nucleic acid polymers, ligand-targeted liposomes and liposomes containing combinations of drugs. These advances have led to numerous clinical trials in such diverse areas as the delivery of anti-cancer, anti-fungal and antibiotic drugs, the delivery of gene medicines, and the delivery of anesthetics and anti-inflammatory drugs. A number of liposomes (lipidic nanoparticles) are on the market, and many more are in the pipeline. Lipidic nanoparticles are the first nanomedicine delivery system to make the transition from concept to clinical application, and they are now an established technology platform with considerable clinical acceptance. We can look forward to many more clinical products in the future.

  18. Calcipotriol delivery into the skin with PEGylated liposomes

    DEFF Research Database (Denmark)

    Knudsen, Nina Østergaard; Rønholt, Stine; Salte, Ragnhild Djønne

    2012-01-01

    The d-vitamin analogue calcipotriol is commonly used for topical treatment of psoriasis, but skin penetration is required for calcipotriol to reach its pharmacological target: the keratinocytes in the lower epidermis. Liposomes can enhance the delivery of drugs into the skin, but a major challenge...... for the development of dosage forms containing liposomes is to maintain the colloidal stability in the formulation. The purpose of this study was to investigate the effect of stabilising liposomes with the lipopolymer poly(ethylene glycol)-distearoylphosphoethanolamine (PEG-DSPE) on the physicochemical properties...... of the liposomes and the ability to deliver membrane-intercalated calcipotriol into the skin. Inclusion of 0.5, l and 5mol% PEG-DSPE in the membrane enhanced the colloidal stability of the liposomes without compromising the delivery of calcipotriol from the vehicle into excised pig skin. Calcipotriol...

  19. The Treatment of Breast Cancer Using Liposome Technology

    Directory of Open Access Journals (Sweden)

    Sarah Brown

    2012-01-01

    Full Text Available Liposome-based chemotherapeutics used in the treatment of breast cancer can in principle enhance the therapeutic index of otherwise unencapsulated anticancer drugs. This is partially attributed to the fact that encapsulation of cytotoxic agents within liposomes allows for increased concentrations of the drug to be delivered to the tumor site. In addition, the presence of the phospholipid bilayer prevents the encapsulated active form of the drug from being broken down in the body prior to reaching tumor tissue and also serves to minimize exposure of the drug to healthy sensitive tissue. While clinically approved liposome-based chemotherapeutics such as Doxil have proven to be quite effective in the treatment of breast cancer, significant challenges remain involving poor drug transfer between the liposome and cancerous cells. In this review, we discuss the recent advancements made in the development of liposome-based chemotherapeutics with respect to improved drug transfer for use in breast cancer therapy.

  20. Ultrasound triggered drug delivery with liposomal nested microbubbles.

    Science.gov (United States)

    Wallace, N; Wrenn, S P

    2015-12-01

    When ultrasound contrast agent microbubbles are nested within a liposome, damage to the liposome membrane caused by both stable and inertial cavitation of the microbubble allows for release of the aqueous core of the liposome. Triggered release was not accomplished unless microbubbles were present within the liposome. Leakage was tested using fluorescence assays developed specifically for this drug delivery vehicle and qualitative measurements using an optical microscope. These studies were done using a 1 MHz focused ultrasound transducer while varying parameters including peak negative ultrasound pressure, average liposome diameter, and microbubble concentration. Two regimes exist for membrane disruption caused by cavitating microbubbles. A faster release rate, as well as permanent membrane damage are seen for samples exposed to high pressure (2.1-3.7 MPa). A slower release rate and dilation/temporary poration are characteristic of stable cavitation for low pressure studies (0.54-1.7 MPa).

  1. Crystalline boron nitride aerogels

    Energy Technology Data Exchange (ETDEWEB)

    Zettl, Alexander K.; Rousseas, Michael; Goldstein, Anna P.; Mickelson, William; Worsley, Marcus A.; Woo, Leta

    2017-04-04

    This disclosure provides methods and materials related to boron nitride aerogels. In one aspect, a material comprises an aerogel comprising boron nitride. The boron nitride has an ordered crystalline structure. The ordered crystalline structure may include atomic layers of hexagonal boron nitride lying on top of one another, with atoms contained in a first layer being superimposed on atoms contained in a second layer.

  2. Liposomes as a gene delivery system

    Directory of Open Access Journals (Sweden)

    C. Ropert

    1999-02-01

    Full Text Available Gene therapy is an active field that has progressed rapidly into clinical trials in a relatively short time. The key to success for any gene therapy strategy is to design a vector able to serve as a safe and efficient gene delivery vehicle. This has encouraged the development of nonviral DNA-mediated gene transfer techniques such as liposomes. Many liposome-based DNA delivery systems have been described, including molecular components for targeting given cell surface receptors or for escaping from the lysosomal compartment. Another recent technology using cationic lipids has been evaluated and has generated substantial interest in this approach to gene transfer.

  3. Boron Nitride Nanotubes

    Science.gov (United States)

    Smith, Michael W. (Inventor); Jordan, Kevin (Inventor); Park, Cheol (Inventor)

    2012-01-01

    Boron nitride nanotubes are prepared by a process which includes: (a) creating a source of boron vapor; (b) mixing the boron vapor with nitrogen gas so that a mixture of boron vapor and nitrogen gas is present at a nucleation site, which is a surface, the nitrogen gas being provided at a pressure elevated above atmospheric, e.g., from greater than about 2 atmospheres up to about 250 atmospheres; and (c) harvesting boron nitride nanotubes, which are formed at the nucleation site.

  4. Boron nitride composites

    Energy Technology Data Exchange (ETDEWEB)

    Kuntz, Joshua D.; Ellsworth, German F.; Swenson, Fritz J.; Allen, Patrick G.

    2017-02-21

    According to one embodiment, a composite product includes: a matrix material including hexagonal boron nitride and one or more borate binders; and a plurality of cubic boron nitride particles dispersed in the matrix material. According to another embodiment, a composite product includes: a matrix material including hexagonal boron nitride and amorphous boron nitride; and a plurality of cubic boron nitride particles dispersed in the matrix material.

  5. Transport of boron by the tassel-less1 aquaporin is critical for vegetative and reproductive development in maize.

    Science.gov (United States)

    Durbak, Amanda R; Phillips, Kimberly A; Pike, Sharon; O'Neill, Malcolm A; Mares, Jonathan; Gallavotti, Andrea; Malcomber, Simon T; Gassmann, Walter; McSteen, Paula

    2014-07-01

    The element boron (B) is an essential plant micronutrient, and B deficiency results in significant crop losses worldwide. The maize (Zea mays) tassel-less1 (tls1) mutant has defects in vegetative and inflorescence development, comparable to the effects of B deficiency. Positional cloning revealed that tls1 encodes a protein in the aquaporin family co-orthologous to known B channel proteins in other species. Transport assays show that the TLS1 protein facilitates the movement of B and water into Xenopus laevis oocytes. B content is reduced in tls1 mutants, and application of B rescues the mutant phenotype, indicating that the TLS1 protein facilitates the movement of B in planta. B is required to cross-link the pectic polysaccharide rhamnogalacturonan II (RG-II) in the cell wall, and the percentage of RG-II dimers is reduced in tls1 inflorescences, indicating that the defects may result from altered cell wall properties. Plants heterozygous for both tls1 and rotten ear (rte), the proposed B efflux transporter, exhibit a dosage-dependent defect in inflorescence development under B-limited conditions, indicating that both TLS1 and RTE function in the same biological processes. Together, our data provide evidence that TLS1 is a B transport facilitator in maize, highlighting the importance of B homeostasis in meristem function.

  6. Development of the Novel PEG-PE-Based Polymer for the Reversible Attachment of Specific Ligands to Liposomes: Synthesis and in vitro Characterization

    Science.gov (United States)

    Biswas, Swati; Dodwadkar, Namita S.; Sawant, Rupa R.; Torchilin, Vladimir P.

    2011-01-01

    Surface grafting of liposomes with the wide variety of ligands including antibodies and other proteins is a promising approach for targeted delivery of therapeutics. In this paper, we describe a simple method of synthesizing a hydrazine-functionalized polyethylene glycol-phosphatidylethanolamine (PEG-PE)-based amphiphilic polymer which can conjugate a variety of ligands via a reversible, pH-cleavable bond. In this method, the targeting ligand is attached to the distal end of the PEG chain, which facilitates its easy access to the targeted site of interaction. The reversible attachment of targeting ligands is useful especially in multifunctional liposomal systems, where after successfully performing the function of targeting to the specific site, the bulky ligands, such as proteins or antibodies, are cleaved off in response to an environmental stimulus to expose some other functionalities such as ligands for intracellular penetration or organelle-specific targeting. To investigate the applicability of the protocol, the model ligands monoclonal antinucleosome antibody 2C5 and antimyosin antibody 2G4, and glycoproteins concanavalin A (Con-A) and avidin were conjugated to the synthesized polymer and incorporated into liposomes. In vitro assays including biochemical, enzyme-linked immunosorbent, fluorescence microscopy and flow cytometry were used to confirm three key characteristics of the modified and/or liposome-attached proteins: successful conjugation of the targeting ligands to the polymer, preservation of specific activity of the ligands after the conjugation and liposome attachment, and the facile pH-sensitive ligand detachment. Monoclonal mAb 2C5 and 2G4, immobilized on the liposome surface, retained their binding affinity to corresponding antigens as confirmed by ELISA. The Con A-bearing liposomes showed significantly higher agglutination in the presence of its substrate mannan compared to plain liposomes (PL) and avidin-functionalized liposomes bound

  7. Liposomal Drug Products: A Quality by Design Approach

    Science.gov (United States)

    Xu, Xiaoming

    Quality by Design (QbD) principles has been applied to the development of two liposomal formulations, containing a hydrophilic small molecule therapeutic (Tenofovir) and a protein therapeutic (superoxide dismutase). The goal of the research is to provide critical information on 1) how to reduce the preparation variability in liposome formulations, and 2) how to increase drug encapsulation inside liposomes to reduce manufacturing cost. Most notably, an improved liposome preparation method was developed which increased the encapsulation efficiency of hydrophilic molecules. In particular, this method allows for very high encapsulation efficiency. For example, encapsulation efficiencies of up to 50% have been achieved, whereas previously only 20% or less have been reported. Another significant outcome from this research is a first principle mathematical model to predict the encapsulation efficiency of hydrophilic drugs in unilamellar liposomes. This mathematical model will be useful in: formulation development to rapidly achieve optimized formulations; comparison of drug encapsulation efficiencies of liposomes prepared using different methods; and assisting in the development of suitable process analytical technologies to achieve real-time monitoring and control of drug encapsulation during manufacturing. A novel two-stage reverse dialysis in vitro release testing method has also been developed for passively targeted liposomes, which uses the first stage to mimic the circulation of liposomes in the body and the second stage to imitate the drug release process at the target. The developed in vitro release testing method can be used to distinguish formulations with varied compositions for quality control testing purposes. This developed method may pave the way to the development of more biorelevant quality control testing methods for liposomal drug products in the future. The QbD case studies performed in this research are examples of how this approach can be used to

  8. Development of theranostic pH-sensitive liposomal nanoparticle for early detection and treatment of colon cancer

    Science.gov (United States)

    Udofot, Ofonime Cosmas

    Purpose: 5-Fluorouracil (5-FU) is a main drug used in the treatment of cancer alone or in combination with other anticancer drugs. 5-FU is associated with poor permeability and short membrane half-life (5-20 min), due to its rapid metabolism in the body. Therefore it has become necessary for the continuous administration of high doses of 5-FU to maintain the minimum therapeutic serum concentration, which gives rise to associated severe side effect, and ultimately lead to severe toxic effect. The aim of this study is to formulate 5-FU-loaded pH-sensitive liposomal nanoparticles (pHLNps-5-FU) and evaluate the 5-FU release characteristics and anticancer effect of pHLNps-5-FU both in vitro and in vivo. Methods: Particle size and zeta potential were determined using particle size analyzer. Release pattern of pHLNps-5-FU formulations was evaluated at 37oC at pH 3, 5, 6.5 and 7.4 while drug release kinetics of 5-FU from pHLNp3--5-FU formulation was determined at pH 3 and 7.4 at different time points (37oC). Cell viability and clonogenic studies were conducted to evaluate the effectiveness of pHLNps-5-FU on HCT-116 and HT-29 cell lines while cellular uptake of rhodamine labeled pHLNps-5-FU was determined by flow cytometry and confocal imaging. The biodistribution and pharmacokinetics parameters of the administered 5-FU and pHLNps-5-FU were compared in nude mice while the efficacy of 5-FU and pHLNps-5-FU were determined in subcutaneous models of HT-29 and HCT-116 mice. Results: The average size of the pHLNps-5-FU liposome was 200 +/- 9.8, 181.9 +/- 9.1 and 164.3 +/- 8.4 nm. In-vitro drug release of 5-FU from pHLNps-5-FU was highest at pH of 3.8 from the different pHLNps-5-FU was observed. Both cells treated with pHLNps-5-FU reduced their viability to 2--3 fold lower compared to that of 5-FU. Flow cytometry and confocal imaging confirmed higher uptake of rhodamine labeled pHLNps-5-FU on both cell lines. Drug release profile of the chosen pHLNp-5-FU was best in pH of 3 and

  9. Temoporfin-loaded liposomes

    DEFF Research Database (Denmark)

    Kuntsche, Judith; Freisleben, Ines; Steiniger, Frank;

    2010-01-01

    some problems associated with the commercial formulation Foscan where the drug is dissolved in a mixture of water-free ethanol and propylene glycol. The present study focuses on the physicochemical characterization of different liposome formulations with special emphasis on the influence of drug...

  10. Targeting cancer with bugs and liposomes: ready, aim, fire.

    Science.gov (United States)

    Cheong, Ian; Huang, Xin; Thornton, Katherine; Diaz, Luis A; Zhou, Shibin

    2007-10-15

    One of the major challenges facing cancer therapy today is achieving specificity. Current efforts to meet this challenge are focused on developing targeted therapeutics specific to the cancer cell. An alternative approach is to selectively deliver cytotoxic agents to the tumor site. With this end in mind, liposomes optimized for physical robustness have been developed and used clinically as drug delivery vehicles. Paradoxically, the effectiveness of these liposomes is hampered by the suboptimal release of bioavailable drug. This article will highlight the recent advance in using a novel lipase secreted by the tumor-colonizing anaerobic bacterium Clostridium novyi-NT to induce the targeted release of liposomal payloads within tumors.

  11. Exploring Cellular Interactions of Liposomes Using Protein Corona Fingerprints and Physicochemical Properties.

    Science.gov (United States)

    Bigdeli, Arafeh; Palchetti, Sara; Pozzi, Daniela; Hormozi-Nezhad, Mohammad Reza; Baldelli Bombelli, Francesca; Caracciolo, Giulio; Mahmoudi, Morteza

    2016-03-22

    To control liposomes fate and transport upon contact with biofluids, it is essential to consider several parameters affecting the synthetic and biological identity of liposomes, as well as liposome-protein corona (PC) aspects. As a powerful tool in this data mining adventure, quantitative structure-activity relationship (QSAR) approach is used to correlate physicochemical properties of liposomes and their PC fingerprints to multiple quantified biological responses. In the present study, the relationship between cellular interactions of a set of structurally diverse liposomal formulations and their physicochemical and PC properties has been investigated via linear and nonlinear QSAR models. Significant parameters affecting cellular uptake and cell viability of liposomes in two important cancer cell lines (PC3 and HeLa) have been identified. The developed QSARs have the capacity to be implemented in advanced targeted delivery of liposomal drugs.

  12. Methods of forming boron nitride

    Science.gov (United States)

    Trowbridge, Tammy L; Wertsching, Alan K; Pinhero, Patrick J; Crandall, David L

    2015-03-03

    A method of forming a boron nitride. The method comprises contacting a metal article with a monomeric boron-nitrogen compound and converting the monomeric boron-nitrogen compound to a boron nitride. The boron nitride is formed on the same or a different metal article. The monomeric boron-nitrogen compound is borazine, cycloborazane, trimethylcycloborazane, polyborazylene, B-vinylborazine, poly(B-vinylborazine), or combinations thereof. The monomeric boron-nitrogen compound is polymerized to form the boron nitride by exposure to a temperature greater than approximately 100.degree. C. The boron nitride is amorphous boron nitride, hexagonal boron nitride, rhombohedral boron nitride, turbostratic boron nitride, wurzite boron nitride, combinations thereof, or boron nitride and carbon. A method of conditioning a ballistic weapon and a metal article coated with the monomeric boron-nitrogen compound are also disclosed.

  13. Development and characterization of high collapse boron alloys heat treated pipes for oil wells; Tubos de aco TiB para aplicacao em revestimento de pocos de petroleo

    Energy Technology Data Exchange (ETDEWEB)

    Moreira, Fabio A.; Silva, Ronaldo; Chad, Luis [Tenaris Confab, Pindamonhangaba SP (Brazil); Fritz, Marcelo C. [Tenaris Confab, Pindamonhangaba SP (Brazil). Dept. de Engenharia do Produto

    2008-07-01

    The utilization of OCTG (Oil Country Tubular Goods) pipes will increase with the discovery of new oil wells in ultra deep waters. This study aims to evaluate the mechanical and microstructural performance of welded and heat treated pipes through quenching and tempering using a steel project based in titanium/boron for casing pipes. The objective of this development is to present a set of techniques used during the manufacturing of heated treated ERW pipes boron allowing, discussing mechanical and metallurgical aspects of the steel project, coil conformation, heat treatment and test procedures. The results are within the limits set by the API 5CT standard. It was found that the pipes obtained good geometry and uniformity of mechanical properties, showing that this product can be applied safely and reliability as wells' casing. (author)

  14. Novel amphiphilic probes for [18F]-radiolabeling preformed liposomes and determination of liposomal trafficking by positron emission tomography.

    Science.gov (United States)

    Urakami, Takeo; Akai, Shuji; Katayama, Yurie; Harada, Norihiro; Tsukada, Hideo; Oku, Naoto

    2007-12-27

    Positron-emission tomography (PET) is a noninvasive real-time functional imaging system and is expected to be useful for the development of new drug candidates in clinical trials. For its application with preformulated liposomes, we devised an optimized [18F]-compound and developed a direct liposome modification method that we termed the "solid-phase transition method". We were successful in using 1-[18F]fluoro-3,6-dioxatetracosane ([18F]7a) for in vivo trafficking of liposomes. This method might be a useful tool in preclinical and clinical studies of lipidic particle-related drugs.

  15. Design, development and characterization of multi-functionalized gold nanoparticles for biodetection and targeted boron delivery in BNCT applications

    Energy Technology Data Exchange (ETDEWEB)

    Mandal, Subhra [Department of Tumor Immunology, Radboud University Nijmegen Medical Centre (Netherlands); Bakeine, Gerald J., E-mail: Jamesbakeine1@yahoo.com [Department of Internal Medicine and Therapeutics-Section of Clinical Toxicology, University of Pavia, Piazza Botta 10, 27100 Pavia (Italy); Krol, Silke [Institute of Neurology, Fondazione IRCCS Carlo Besta, Milan (Italy); Ferrari, Cinzia; Clerici, Anna M.; Zonta, Cecilia; Cansolino, Laura [Department of Surgery, Laboratory of Experimental Surgery, University of Pavia (Italy); Ballarini, Francesca [Department of Nuclear and Theoretical Physics, University of Pavia (Italy); Bortolussi, Silva [Department of Nuclear and Theoretical Physics, University of Pavia (Italy)] [National Institute of Nuclear Physics (INFN), Section of Pavia (Italy); Stella, Subrina; Protti, Nicoletta [Department of Nuclear and Theoretical Physics, University of Pavia (Italy); Bruschi, Piero [National Institute of Nuclear Physics (INFN), Section of Pavia (Italy); Altieri, Saverio [Department of Nuclear and Theoretical Physics, University of Pavia (Italy)] [National Institute of Nuclear Physics (INFN), Section of Pavia (Italy)

    2011-12-15

    The aim of this study is to optimize targeted boron delivery to cancer cells and its tracking down to the cellular level. To this end, we describe the design and synthesis of novel nanovectors that double as targeted boron delivery agents and fluorescent imaging probes. Gold nanoparticles were coated with multilayers of polyelectrolytes functionalized with the fluorescent dye (FITC), boronophenylalanine and folic acid. In vitro confocal fluorescence microscopy demonstrated significant uptake of the nanoparticles in cancer cells that are known to overexpress folate receptors. - Highlights: Black-Right-Pointing-Pointer Synthesis of multi-labeled gold nanoparticles for selective boron delivery to tumor cells. Black-Right-Pointing-Pointer Tumor selectivity is achieved through folic acid receptor targeting. Black-Right-Pointing-Pointer Optical fluorescent microscopy allows tracking of cellular uptake of the gold nanoparticle. Black-Right-Pointing-Pointer In vitro tests demonstrate selective nanoparticle up in folate receptor positive tumor cells.

  16. The adjuvant mechanism of cationic dimethyldioctadecylammonium liposomes

    DEFF Research Database (Denmark)

    Korsholm, Karen Smith; Agger, Else Marie; Foged, Camilla;

    2007-01-01

    Cationic liposomes are being used increasingly as efficient adjuvants for subunit vaccines but their precise mechanism of action is still unknown. Here, we investigated the adjuvant mechanism of cationic liposomes based on the synthetic amphiphile dimethyldioctadecylammonium (DDA). The liposomes ...

  17. Impact of atomization technique on the stability and transport efficiency of nebulized liposomes harboring different surface characteristics.

    Science.gov (United States)

    Lehofer, Bernhard; Bloder, Florian; Jain, Pritesh P; Marsh, Leigh M; Leitinger, Gerd; Olschewski, Horst; Leber, Regina; Olschewski, Andrea; Prassl, Ruth

    2014-11-01

    The objective of this study was to evaluate the impact of nebulization on liposomes with specific surface characteristics by applying three commercially available inhaler systems (air-jet, ultrasonic and vibrating-mesh). Conventional liposome formulations composed of phosphatidylcholine and cholesterol were compared to sterically stabilized PEGylated liposomes and cationic polymer coated liposomes.Liposomes of similar size (between 140 and 165 nm in diameter with polydispersity indices atomization process, while polymer coated and especially positively charged liposomes showed enhanced leakage. The release rates for the hydrophilic model drug system were highest for the vibrating-mesh nebulizers regardless of the surface characteristics of the liposomes (increasing from 10% to 20% and 50% for the conventional, PEGylated and positively charged formulations, respectively). In view of surface modified liposomes our data suggest that drug delivery via nebulization necessitates the finding of a compromise between nebulizer efficiency, formulation stability and drug release profile to accomplish the development of tailored formulations suitable for advanced inhalation therapy.

  18. Liposomes to target peripheral neurons and Schwann cells.

    Directory of Open Access Journals (Sweden)

    Sooyeon Lee

    Full Text Available While a wealth of literature for tissue-specific liposomes is emerging, optimal formulations to target the cells of the peripheral nervous system (PNS are lacking. In this study, we asked whether a novel formulation of phospholipid-based liposomes could be optimized for preferential uptake by microvascular endothelia, peripheral neurons and Schwann cells. Here, we report a unique formulation consisting of a phospholipid, a polymer surfactant and cholesterol that result in enhanced uptake by targeted cells. Using fluorescently labeled liposomes, we followed particle internalization and trafficking through a distinct route from dextran and escape from degradative compartments, such as lysosomes. In cultures of non-myelinating Schwann cells, liposomes associate with the lipid raft marker Cholera toxin, and their internalization is inhibited by disruption of lipid rafts or actin polymerization. In contrast, pharmacological inhibition of clathrin-mediated endocytosis does not significantly impact liposome entry. To evaluate the efficacy of liposome targeting in tissues, we utilized myelinating explant cultures of dorsal root ganglia and isolated diaphragm preparations, both of which contain peripheral neurons and myelinating Schwann cells. In these models, we detected preferential liposome uptake into neurons and glial cells in comparison to surrounding muscle tissue. Furthermore, in vivo liposome administration by intramuscular or intravenous injection confirmed that the particles were delivered to myelinated peripheral nerves. Within the CNS, we detected the liposomes in choroid epithelium, but not in myelinated white matter regions or in brain parenchyma. The described nanoparticles represent a novel neurophilic delivery vehicle for targeting small therapeutic compounds, biological molecules, or imaging reagents into peripheral neurons and Schwann cells, and provide a major advancement toward developing effective therapies for peripheral

  19. Liposome/water lipophilicity: methods, information content, and pharmaceutical applications.

    Science.gov (United States)

    van Balen, Georgette Plemper; Martinet, Catherine a Marca; Caron, Giulia; Bouchard, Géraldine; Reist, Marianne; Carrupt, Pierre-Alain; Fruttero, Roberta; Gasco, Alberto; Testa, Bernard

    2004-05-01

    This review discusses liposome/water lipophilicity in terms of the structure of liposomes, experimental methods, and information content. In a first part, the structural properties of the hydrophobic core and polar surface of liposomes are examined in the light of potential interactions with solute molecules. Particular emphasis is placed on the physicochemical properties of polar headgroups of lipids in liposomes. A second part is dedicated to three useful methods to study liposome/water partitioning, namely potentiometry, equilibrium dialysis, and (1)H-NMR relaxation rates. In each case, the principle and limitations of the method are discussed. The next part presents the structural information encoded in liposome/water lipophilicity, in other words the solutes' structural and physicochemical properties that determine their behavior and hence their partitioning in such systems. This presentation is based on a comparison between isotropic (i.e., solvent/water) and anisotropic (e.g., liposome/water) systems. An important factor to be considered is whether the anisotropic lipid phase is ionized or not. Three examples taken from the authors' laboratories are discussed to illustrate the factors or combinations thereof that govern liposome/water lipophilicity, namely (a) hydrophobic interactions alone, (b) hydrophobic and polar interactions, and (c) conformational effects plus hydrophobic and ionic interactions. The next part presents two studies taken from the field of QSAR to exemplify the use of liposome/water lipophilicity in structure-disposition and structure-activity relationships. In the conclusion, we summarize the interests and limitations of this technology and point to promising developments.

  20. In vivo and in vitro evaluation of octyl methoxycinnamate liposomes

    Science.gov (United States)

    Varjão Mota, Aline de Carvalho; Faria de Freitas, Zaida Maria; Júnior, Eduardo Ricci; Dellamora-Ortiz, Gisela Maria; Santos-Oliveira, Ralph; Ozzetti, Rafael Antonio; Vergnanini, André Luiz; Ribeiro, Vanessa Lira; Silva, Ronald Santos; dos Santos, Elisabete Pereira

    2013-01-01

    Solar radiation causes damage to human skin, and photoprotection is the main way to prevent these harmful effects. The development of sunscreen formulations containing nanosystems is of great interest in the pharmaceutical and cosmetic industries because of the many potential benefits. This study aimed to develop and evaluate an octyl methoxycinnamate (OMC) liposomal nanosystem (liposome/OMC) to obtain a sunscreen formulation with improved safety and efficacy by retaining OMC for longer on the stratum corneum. Methods The liposome/OMC nanostructure obtained was tested for enzymatic hydrolysis with lipase from Rhizomucor miehei and biodistribution with liposomes labeled with technetium-99m. The liposome/OMC formulation was then incorporated in a gel formulation and tested for ocular irritation using the hen’s egg test-chorio-allantoic membrane (HET-CAM) assay, in vitro and in vivo sun protection factor, in vitro release profile, skin biometrics, and in vivo tape stripping. Results The liposome/OMC nanosystem was not hydrolyzed from R. miehei by lipase. In the biodistribution assay, the liposome/OMC formulation labeled with technetium-99m had mainly deposited in the skin, while for OMC the main organ was the liver, showing that the liposome had higher affinity for the skin than OMC. The liposome/OMC formulation was classified as nonirritating in the HET-CAM test, indicating good histocompatibility. The formulation containing liposome/OMC had a higher in vivo solar photoprotection factor, but did not show increased water resistance. Inclusion in liposomes was able to slow down the release of OMC from the formulation, with a lower steady-state flux (3.9 ± 0.33 μg/cm2/hour) compared with the conventional formulation (6.3 ± 1.21 μg/cm2/hour). The stripping method showed increased uptake of OMC in the stratum corneum, giving an amount of 22.64 ± 7.55 μg/cm2 of OMC, which was higher than the amount found for the conventional formulation (14.57 ± 2.30 μg/cm2

  1. X-ray diffraction study of boron produced by pyrolysis of boron tribromide

    Science.gov (United States)

    Rosenberg, David

    The goal of this research was to determine the composition of boron deposits produced by pyrolysis of boron tribromide, and to use the results to (a) determine the experimental conditions (reaction temperature, etc.) necessary to produce alpha-rhombohedral boron and (b) guide the development/refinement of the pyrolysis experiments such that large, high purity crystals of alpha-rhombohedral boron can be produced with consistency. Developing a method for producing large, high purity alpha-rhombohedral boron crystals is of interest because such crystals could potentially be used to achieve an alpha-rhombohedral boron based neutron detector design (a solid-state detector) that could serve as an alternative to existing neutron detector technologies. The supply of neutron detectors in the United States has been hampered for a number of years due to the current shortage of helium-3 (a gas used in many existing neutron detector technologies); the development of alternative neutron detector technology such as an alpha-rhombohedral boron based detector would help provide a more sustainable supply of neutron detectors in this country. In addition, the prospect/concept of an alpha-rhombohedral boron based neutron detector is attractive because it offers the possibility of achieving a design that is smaller, longer life, less power consuming, and potentially more sensitive than existing neutron detectors. The main difficulty associated with creating an alpha-rhombohedral boron based neutron detector is that producing large, high purity crystals of alpha-rhombohedral boron is extremely challenging. Past researchers have successfully made alpha-rhombohedral boron via a number of methods, but no one has developed a method for consistently producing large, high purity crystals. Alpha-rhombohedral boron is difficult to make because it is only stable at temperatures below around 1100-1200 °C, its formation is very sensitive to impurities, and the conditions necessary for its

  2. A Remote Controlled Valve in Liposomes for Triggered Liposomal Release

    NARCIS (Netherlands)

    Koçer, Armağan

    2007-01-01

    In order to reduce the toxicity and increase the efficacy of drugs, there is a need for smart drug delivery systems. Liposomes are one of the promising tools for this purpose. An ideal liposomal delivery system should be stable, long-circulating, accumulate at the target site and release its drug in

  3. Doses de boro no desenvolvimento de copo-de-leite em solução nutritiva Boron doses in the development of calla lily in nutrient solution

    Directory of Open Access Journals (Sweden)

    Roseane Rodrigues de Souza

    2010-12-01

    Full Text Available O boro desempenha funções importantes em processos biológicos das plantas, como a síntese e estruturação da parede celular, lignificação, metabolismo e transporte de carboidratos, além de participar da divisão e diferenciação celular em tecidos meristemáticos. No entanto, as necessidades nutricionais para o cultivo de copo-de-leite, especialmente de boro, ainda são pouco conhecidas. Assim, objetivou-se avaliar os efeitos de diferentes doses de boro no crescimento e desenvolvimento, teor e acúmulo desse nutriente em plantas de copo-de-leite cultivadas em solução nutritiva. Mudas micropropagadas foram submetidas aos tratamentos com as doses de 0,05; 0,25; 0,50; 0,75; 1,00 e 2,00 mg L-1 de boro em solução nutritiva de Hoagland & Arnon diluída a 30% de sua força iônica. O delineamento experimental foi o inteiramente casualizado, com dez repetições. As plantas não manifestaram sintomas visuais de deficiência ou de toxidez de boro, no entanto, o sistema radicular das plantas cultivadas na dose de 0,05 mg L-1 de boro apresentou-se com o crescimento reduzido. A melhor dose para o desenvolvimento adequado de plantas de copo-de-leite em solução nutritiva é de 1,20 mg L-1 de boro.Boron has essential functions in plant biological processes such as cell wall synthesis and structuralization, lignification, carbohydrates metabolism and transport. This element also acts in cell division and differentiation in meristematic tissues. However, the nutritional needs for calla lily cultivation, and especially boron needs, are still poorly known. Thus, the objective of this work was to evaluate the effects of different boron doses on growth and development, content and accumulation of boron in calla lily plants grown in a nutrient solution. Micropropagated seedlings were submitted to treatments with the doses 0.05; 0.25; 0.50; 0.75; 1.00 and 2.00 mg L-1 boron in Hoagland & Arnon nutrient solution diluted to 30% of its ionic force. The

  4. Boron nitride converted carbon fiber

    Science.gov (United States)

    Rousseas, Michael; Mickelson, William; Zettl, Alexander K.

    2016-04-05

    This disclosure provides systems, methods, and apparatus related to boron nitride converted carbon fiber. In one aspect, a method may include the operations of providing boron oxide and carbon fiber, heating the boron oxide to melt the boron oxide and heating the carbon fiber, mixing a nitrogen-containing gas with boron oxide vapor from molten boron oxide, and converting at least a portion of the carbon fiber to boron nitride.

  5. Liposomal Encapsulated Rhodomyrtone: A Novel Antiacne Drug

    Directory of Open Access Journals (Sweden)

    Julalak Chorachoo

    2013-01-01

    Full Text Available Rhodomyrtone isolated from the leaves of Rhodomyrtus tomentosa possesses antibacterial, anti-inflammatory, and anti-oxidant activities. Since rhodomyrtone is insoluble in water, it is rather difficult to get to the target sites in human body. Liposome exhibited ability to entrap both hydrophilic and hydrophobic compounds and easily penetrate to the target site. The present study aimed to develop a novel liposomal encapsulated rhodomyrtone formulations. In addition, characterization of liposome, stability profiles, and their antiacne activity were performed. Three different formulations of total lipid concentrations 60, 80, and 100 μmol/mL were used. Formulation with 60 μmol/mL total lipid (phosphatidylcholine from soybean and cholesterol from lanolin in 4 : 1, w/w exhibited the highest rhodomyrtone encapsulation efficacy (65.47 ± 1.7%, average particle size (209.56 ± 4.8 nm, and ζ-potential (–41.19 ± 1.3 mV. All formulations demonstrated good stability when stored for 2 months in dark at 4°C as well as room temperature. Minimal inhibitory concentration and minimal bactericidal concentration values of liposomal formulation against 11 clinical bacterial isolates and reference strains ranged from 1 to 4 and from 4 to 64 μg/mL, respectively, while those of rhodomyrtone were 0.25–1 and 0.5–2 μg/mL, respectively. The MIC and MBC values of liposome formulation were more effective than topical drugs against Staphylococcus aureus and Staphylococcus epidermidis.

  6. An evaluation of anti-tumor effect and toxicity of PEGylated ursolic acid liposomes

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Qianqian; Zhao, Tingting; Liu, Yanping; Xing, Shanshan; Li, Lei; Gao, Dawei, E-mail: dwgao@ysu.edu.cn [Yanshan University, Applying Chemistry Key Lab of Hebei Province, Department of Bioengineer (China)

    2016-02-15

    Therapy of solid tumors mediated by nano-drug delivery has attracted considerable interest. In our previous study, ursolic acid (UA) was successfully encapsulated into PEGylated liposomes. The study aimed to evaluate the tumor inhibition effect and cytotoxicity of the PEGylated UA liposomes by U14 cervical carcinoma-bearing mice. The liposomes were spherical particles with mean particle diameters of 127.2 nm. The tumor inhibition rate of PEGylated UA liposomes was 53.60 % on U14 cervical carcinoma-bearing mice, which was greater than those of the UA solution (18.25 %) and traditional UA liposome groups (40.75 %). The tumor cells apoptosis rate of PEGylated UA liposomes was 25.81 %, which was significantly higher than that of the traditional UA liposomes (13.37 %). Moreover, the kidney and liver did not emerge the pathological changes in UA therapeutic mice by histopathological analysis, while there were significant differences on tumor tissues among three UA formulation groups. The PEGylated UA liposomes exhibited higher anti-tumor activity and lower cytotoxicity, and the main reason was that the coating PEG layer improved UA liposome properties, such as enhancing the stability of liposomes, promoting the effect of slow release, and prolonging the time of blood circulation. This may shed light on the development of PEGylated nano-vehicles.

  7. A Liposomal Formulation Able to Incorporate a High Content of Paclitaxel and Exert Promising Anticancer Effect

    Directory of Open Access Journals (Sweden)

    Pei Kan

    2011-01-01

    Full Text Available A liposome formulation for paclitaxel was developed in this study. The liposomes, composed of naturally unsaturated and hydrogenated phosphatidylcholines, with significant phase transition temperature difference, were prepared and characterized. The liposomes exhibited a high content of paclitaxel, which was incorporated within the segregated microdomains coexisting on phospholipid bilayer of liposomes. As much as 15% paclitaxel to phospholipid molar ratio were attained without precipitates observed during preparation. In addition, the liposomes remained stable in liquid form at 4∘C for at least 6 months. The special composition of liposomal membrane which could reduce paclitaxel aggregation could account for such a capacity and stability. The cytotoxicity of prepared paclitaxel liposomes on the colon cancer C-26 cell culture was comparable to Taxol. Acute toxicity test revealed that LD50 for intravenous bolus injection in mice exceeded by 40 mg/kg. In antitumor efficacy study, the prepared liposomal paclitaxel demonstrated the increase in the efficacy against human cancer in animal model. Taken together, the novel formulated liposomes can incorporate high content of paclitaxel, remaining stable for long-term storage. These animal data also demonstrate that the liposomal paclitaxel is promising for further clinical use.

  8. Development of a Tandem-Electrostatic-Quadrupole facility for Accelerator-Based Boron Neutron Capture Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Kreiner, A.J., E-mail: kreiner@tandar.cnea.gov.ar [Gerencia de Investigacion y Aplicaciones, Comision Nacional de Energia Atomica, Av. Gral Paz 1499, 1650 San Martin, Buenos Aires (Argentina)] [Escuela de Ciencia y Tecnologia, Universidad Nacional de San Martin (Argentina)] [CONICET, Buenos Aires (Argentina); Castell, W. [Gerencia de Investigacion y Aplicaciones, Comision Nacional de Energia Atomica, Av. Gral Paz 1499, 1650 San Martin, Buenos Aires (Argentina); Di Paolo, H. [Gerencia de Investigacion y Aplicaciones, Comision Nacional de Energia Atomica, Av. Gral Paz 1499, 1650 San Martin, Buenos Aires (Argentina)] [Escuela de Ciencia y Tecnologia, Universidad Nacional de San Martin (Argentina); Baldo, M. [Gerencia de Investigacion y Aplicaciones, Comision Nacional de Energia Atomica, Av. Gral Paz 1499, 1650 San Martin, Buenos Aires (Argentina); Bergueiro, J. [Gerencia de Investigacion y Aplicaciones, Comision Nacional de Energia Atomica, Av. Gral Paz 1499, 1650 San Martin, Buenos Aires (Argentina)] [CONICET, Buenos Aires (Argentina)

    2011-12-15

    We describe the present status of an ongoing project to develop a Tandem-ElectroStatic-Quadrupole (TESQ) accelerator facility for Accelerator-Based (AB)-BNCT. The project final goal is a machine capable of delivering 30 mA of 2.4 MeV protons to be used in conjunction with a neutron production target based on the {sup 7}Li(p,n){sup 7}Be reaction. The machine currently being constructed is a folded TESQ with a high-voltage terminal at 0.6 MV. We report here on the progress achieved in a number of different areas.

  9. Light activated liposomes: Functionality and prospects in ocular drug delivery.

    Science.gov (United States)

    Lajunen, Tatu; Nurmi, Riikka; Kontturi, Leena; Viitala, Lauri; Yliperttula, Marjo; Murtomäki, Lasse; Urtti, Arto

    2016-12-28

    Ocular drug delivery, especially to the retina and choroid, is a major challenge in drug development. Liposome technology may be useful in ophthalmology in enabling new routes of delivery, prolongation of drug action and intracellular drug delivery, but drug release from the liposomes should be controlled. For that purpose, light activation may be an approach to release drug at specified time and site in the eye. Technical advances have been made in the field of light activated drug release, particularly indocyanine green loaded liposomes are a promising approach with safe materials and effective light triggered release of small and large molecules. This review discusses the liposomal drug delivery with light activated systems in the context of ophthalmic drug delivery challenges.

  10. Liposome surface charge influence on skin penetration behaviour.

    Science.gov (United States)

    Gillet, A; Compère, P; Lecomte, F; Hubert, P; Ducat, E; Evrard, B; Piel, G

    2011-06-15

    Vesicular systems have shown their ability to increase dermal and transdermal drug delivery. Their mechanism of drug transport into and through the skin has been investigated but remains a much debated question. Several researchers have outlined that drug penetration can be influenced by modifying the surface charge of liposomes. In the present work we study the influence of particle surface charge on skin penetration. The final purpose is the development of a carrier system which is able to enhance the skin delivery of two model drugs, betamethasone and betamethasone dipropionate. Liposomes were characterised by their size, morphology, zeta potential, encapsulation efficiency and stability. Ex vivo diffusion studies using Franz diffusion cells were performed. Confocal microscopy was performed to visualise the penetration of fluorescently labelled liposomes into the skin. This study showed the potential of negatively charged liposomes to enhance the skin penetration of betamethasone and betamethasone dipropionate.

  11. Power Burst Facility/Boron Neutron Capture Therapy Program for cancer treatment

    Energy Technology Data Exchange (ETDEWEB)

    Ackermann, A.L. (ed.); Dorn, R.V. III.

    1990-08-01

    This report discusses monthly progress in the Power Boron Facility/Boron Neutron Capture Therapy (PBF/BNCT) Program for Cancer Treatment. Highlights of the PBF/BNCT Program during August 1990 include progress within the areas of: Gross Boron Analysis in Tissue, Blood, and Urine, boron microscopic (subcellular) analytical development, noninvasive boron quantitative determination, analytical radiation transport and interaction modeling for BNCT, large animal model studies, neutron source and facility preparation, administration and common support and PBF operations.

  12. Science Letters:Development of supported boron-doping TiO2 catalysts by chemical vapor deposition

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    In this study, supported nonmetal (boron) doping TiO2 coating photocatalysts were prepared by chemical vapor deposition (CVD) to enhance the activity under visible light irradiation and avoid the recovering of TiO2. Boron atoms were successfully doped into the lattice of TiO2 through CVD, as evidenced from XPS analysis. B-doped TiO2 coating catalysts showed drastic and strong absorption in the visible light range with a red shift in the band gap transition. This novel B-TiO2 coating photocatalyst showed higher photocatalytic activity in methyl orange degradation under visible light irradiation than that of the pure TiO2 photocatalyst.

  13. Development of high intensity ion sources for a Tandem-Electrostatic-Quadrupole facility for Accelerator-Based Boron Neutron Capture Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Bergueiro, J. [Gerencia de Investigacion y Aplicaciones, Comision Nacional de Energia Atomica (Argentina)] [CONICET, Buenos Aires (Argentina); Igarzabal, M.; Suarez Sandin, J.C. [Gerencia de Investigacion y Aplicaciones, Comision Nacional de Energia Atomica (Argentina); Somacal, H.R. [Gerencia de Investigacion y Aplicaciones, Comision Nacional de Energia Atomica (Argentina)] [Escuela de Ciencia y Tecnologia, Universidad Nacional de San Martin (Argentina); Thatar Vento, V. [Gerencia de Investigacion y Aplicaciones, Comision Nacional de Energia Atomica (Argentina)] [CONICET, Buenos Aires (Argentina); Huck, H.; Valda, A.A. [Gerencia de Investigacion y Aplicaciones, Comision Nacional de Energia Atomica (Argentina)] [Escuela de Ciencia y Tecnologia, Universidad Nacional de San Martin (Argentina); Repetto, M. [Gerencia de Investigacion y Aplicaciones, Comision Nacional de Energia Atomica (Argentina)

    2011-12-15

    Several ion sources have been developed and an ion source test stand has been mounted for the first stage of a Tandem-Electrostatic-Quadrupole facility For Accelerator-Based Boron Neutron Capture Therapy. A first source, designed, fabricated and tested is a dual chamber, filament driven and magnetically compressed volume plasma proton ion source. A 4 mA beam has been accelerated and transported into the suppressed Faraday cup. Extensive simulations of the sources have been performed using both 2D and 3D self-consistent codes.

  14. Recent advances in liposomal dry powder formulations: preparation and evaluation.

    Science.gov (United States)

    Misra, Ambikanandan; Jinturkar, Kaustubh; Patel, Deepa; Lalani, Jigar; Chougule, Mahavir

    2009-01-01

    Liposomal drug dry powder formulations have shown many promising features for pulmonary drug administration, such as selective localization of drug within the lung, controlled drug release, reduced local and systemic toxicities, propellant-free nature, patient compliance, high dose carrying capacity, stability and patent protection. Critical review of the recent developments will provide a balanced view on benefits of liposomal encapsulation while developing dry powder formulations and will help researchers to update themselves and focus their research in more relevant areas. In liposomal dry powder formulations (LDPF), drug encapsulated liposomes are homogenized, dispersed into the carrier and converted into dry powder form by using freeze drying, spray drying and spray freeze drying. Alternatively, LDPF can also be formulated by supercritical fluid technologies. On inhalation with a suitable inhalation device, drug encapsulated liposomes get rehydrated in the lung and release the drug over a period of time. The prepared LDPF are evaluated in vitro and in vivo for lung deposition behavior and drug disposition in the lung using a suitable inhaler device. The most commonly used liposomes are composed of lung surfactants and synthetic lipids. Delivery of anticancer agents for lung cancer, corticosteroids for asthma, immunosuppressants for avoiding lung transplantation rejection, antifungal drugs for lung fungal infections, antibiotics for local pulmonary infections and cystic fibrosis and opioid analgesics for pain management using liposome technology are a few examples. Many liposomal formulations have reached the stage of clinical trials for the treatment of pulmonary distress, cystic fibrosis, lung fungal infection and lung cancer. These formulations have given very promising results in both in vitro and in vivo studies. However, modifications to new therapies for respiratory diseases and systemic delivery will provide new challenges in conducting well

  15. Use of enzyme label for quantitative evaluation of liposome adhesion on cell surface: studies with J774 macrophage monolayers.

    Science.gov (United States)

    Trubetskoy, V S; Dormeneva, E V; Tsibulsky, V P; Repin, V S; Torchilin, V P

    1988-07-01

    A method for quantitation of cell surface-bound liposomes utilizing J774 macrophage monolayers is developed. Surface-bound biotinyl-containing and 125I-labeled liposomes were quantified with avidin-peroxidase in an ELISA-like assay. Peroxidase substrate absorbance values were recalculated into the absolute amount of liposomal lipid using a special calibration plot. Total liposome uptake by macrophages was determined following the binding of 125I radioactivity. The approach suggested allows quantitative evaluation of the changes in the content of surface-adhered liposomes during their interaction with cells in vitro.

  16. Developing scandium and zirconium containing aluminum boron carbide metal matrix composites for high temperature applications

    Science.gov (United States)

    Lai, Jing

    The study presented in this thesis focuses on developing castable, precipitation-strengthened Al--B4C metal matrix composites (MMCs) for high temperature applications. In the first part, B4C plates were immersed in liquid aluminum alloyed with Sc, Zr and Ti to investigate the interfacial reactions between B4C and liquid aluminum The influences of Sc, Zr and Ti on the interfacial microstructure in terms of individual and combined additions were examined. Results reveal that all three elements reacted with B4C and formed interfacial layers that acted as a diffusion barrier to limit the decomposition of B4C in liquid aluminum. The interfacial reactions and the reaction products in each system were identified. With the combined addition of Sc, Zr and Ti, most of the Ti was found to enrich at the interface, which not only offered appropriate protection of the B4C but also reduced the consumption of Sc and Zr at the interface. In the second part, Sc and Zr were introduced into Al-15vol.% B 4C composites presaturated by Ti, and eight experimental composites with different Sc and Zr levels were prepared via a conventional casting technique. It was found that Sc was involved in the interfacial reactions with B 4C that partially consume Sc. The Sc addition yielded considerable precipitation strengthening in the as-cast and peak aged conditions. To achieve an equivalent strengthening effect of Sc in binary Al-Sc alloys, approximately double the amount of Sc is required in Al-B4C composites. On the contrary, no major Zr reaction products were found at the interfaces and the major part of Zr remained in the matrix for the precipitation strengthening. The combination of Sc and Zr enhanced sthe precipitation strengthening. Two kinds of nanoscale precipitates, Al3Sc and Al3(Sc, Zr), were found in the as-cast microstructure and contributed to the increase in the matrix hardness. In the third part, all the experimental composites were isothermally aged at 300, 350, 400 and 450

  17. Boron-10 loaded inorganic shielding material

    Science.gov (United States)

    Baker, S. I.; Ryskiewicz, R. S.

    1972-01-01

    Shielding material containing Boron 10 and gadoliunium for neutron absorption has been developed to reduce interference from low energy neutrons in measurement of fission neutron spectrum using Li-6 fast neutron spectrometer.

  18. The antimicrobial activity of liposomal lauric acids against Propionibacterium acnes.

    Science.gov (United States)

    Yang, Darren; Pornpattananangkul, Dissaya; Nakatsuji, Teruaki; Chan, Michael; Carson, Dennis; Huang, Chun-Ming; Zhang, Liangfang

    2009-10-01

    This study evaluated the antimicrobial activity of lauric acid (LA) and its liposomal derivatives against Propionibacterium acnes (P. acnes), the bacterium that promotes inflammatory acne. First, the antimicrobial study of three free fatty acids (lauric acid, palmitic acid and oleic acid) demonstrated that LA gives the strongest bactericidal activity against P. acnes. However, a setback of using LA as a potential treatment for inflammatory acne is its poor water solubility. Then the LA was incorporated into a liposome formulation to aid its delivery to P. acnes. It was demonstrated that the antimicrobial activity of LA was not only well maintained in its liposomal derivatives but also enhanced at low LA concentration. In addition, the antimicrobial activity of LA-loaded liposomes (LipoLA) mainly depended on the LA loading concentration per single liposomes. Further study found that the LipoLA could fuse with the membranes of P. acnes and release the carried LA directly into the bacterial membranes, thereby killing the bacteria effectively. Since LA is a natural compound that is the main acid in coconut oil and also resides in human breast milk and liposomes have been successfully and widely applied as a drug delivery vehicle in the clinic, the LipoLA developed in this work holds great potential of becoming an innate, safe and effective therapeutic medication for acne vulgaris and other P. acnes associated diseases.

  19. Biological activity of liposomal vanillin.

    Science.gov (United States)

    Castan, Leniher; Del Toro, Grisel; Fernández, Adolfo A; González, Manuel; Ortíz, Emilia; Lobo, Daliana

    2013-06-01

    This article presents a study of vanillin encapsulation inside multilamellar liposomes, with emphasis on the evaluation of antioxidant activity, the hemolytic effect, and the antisickling properties of these products. Egg phosphatidylcholine-cholesterol and egg phosphatidylcholine-cholesterol-1-O-decylglycerol liposomes were prepared by mechanical dispersion, all with vanillin included. Vesicles were characterized by determination of encapsulation efficiency and vanillin retention capacity. Antioxidant activity was determined by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method. The hemolytic effect of liposomes was also evaluated by spectrophotometry, as well as the antisickling activity by the Huck test using optical microscopy. Results showed that the lipid composition of liposomes did not significantly affect the encapsulation efficiency. Stable vesicles were obtained with a high retention percentage of vanillin. Liposomes exhibited a high capture of the DPPH radical compared to free vanillin and 1-O-decylglycerol (C10) in solution. Vesicles caused no significant hemolisys in normal erythrocytes, nor in those coming from patients with sickle cell anemia. Vanillin encapsulated in liposomes retained its antisickling activity, with a greater effect for C10-containing vesicles. Our results show that vanillin encapsulation in liposomes is a way to enhance the pharmacologic properties of this molecule using a suitable vehicle.

  20. Tablets of pre-liposomes govern in situ formation of liposomes: concept and potential of the novel drug delivery system.

    Science.gov (United States)

    Vanić, Željka; Planinšek, Odon; Škalko-Basnet, Nataša; Tho, Ingunn

    2014-10-01

    The purpose of this study was to develop a novel drug delivery system for challenging drugs with potential for scale-up manufacturing and controlled release of incorporated drug. Pre-liposomes powder containing metronidazole, lecithin and mannitol, prepared by spray-drying, was mixed with different tableting excipients (microcrystalline cellulose, lactose monohydrate, mannitol, dibasic calcium phosphate, pregelatinized starch, pectin or chitosan) and compressed into tablets. The delivery system was characterized with respect to (i) dry powder characteristics, (ii) mechanical tablet properties and drug release, and (iii) liposomal characteristics. The pre-liposomes powder was free-flowing, and tablets of similarly high qualities as tablets made of physical mixtures were prepared with all excipients. Liposomes were formed in situ upon tablet disintegration, dissolution or erosion depending on the type of tablet excipient used. The liposomal characteristics and drug release were found to depend on the tablet excipient. The new delivery system offers a unique synergy between the ability of liposomes to encapsulate and protect drugs and increased stability provided by compressed formulations. It can be adjusted for drug administration via various routes, e.g. oral, buccal and vaginal.

  1. Combustion synthesis of novel boron carbide

    Science.gov (United States)

    Harini, R. Saai; Manikandan, E.; Anthonysamy, S.; Chandramouli, V.; Eswaramoorthy, D.

    2013-02-01

    The solid-state boron carbide is one of the hardest materials known, ranking third behind diamond and cubic boron nitride. Boron carbide (BxCx) enriched in the 10B isotope is used as a control rod material in the nuclear industry due to its high neutron absorption cross section and other favorable physico-chemical properties. Conventional methods of preparation of boron carbide are energy intensive processes accompanied by huge loss of boron. Attempts were made at IGCAR Kalpakkam to develop energy efficient and cost effective methods to prepare boron carbide. The products of the gel combustion and microwave synthesis experiments were characterized for phase purity by XRD. The carbide formation was ascertained using finger-print spectroscopy of FTIR. Samples of pyrolized/microwave heated powder were characterized for surface morphology using SEM. The present work shows the recent advances in understanding of structural and chemical variations in boron carbide and their influence on morphology, optical and vibrational property results discussed in details.

  2. Development of a dual phantom technique for measuring the fast neutron component of dose in boron neutron capture therapy

    Energy Technology Data Exchange (ETDEWEB)

    Sakurai, Yoshinori, E-mail: yosakura@rri.kyoto-u.ac.jp; Tanaka, Hiroki; Kondo, Natsuko; Kinashi, Yuko; Suzuki, Minoru; Masunaga, Shinichiro; Ono, Koji; Maruhashi, Akira [Kyoto University Research Reactor Institute, Asashironishi 2-1010, Kumatori-cho, Sennan-gun, Osaka 590-0494 (Japan)

    2015-11-15

    Purpose: Research and development of various accelerator-based irradiation systems for boron neutron capture therapy (BNCT) is underway throughout the world. Many of these systems are nearing or have started clinical trials. Before the start of treatment with BNCT, the relative biological effectiveness (RBE) for the fast neutrons (over 10 keV) incident to the irradiation field must be estimated. Measurements of RBE are typically performed by biological experiments with a phantom. Although the dose deposition due to secondary gamma rays is dominant, the relative contributions of thermal neutrons (below 0.5 eV) and fast neutrons are virtually equivalent under typical irradiation conditions in a water and/or acrylic phantom. Uniform contributions to the dose deposited from thermal and fast neutrons are based in part on relatively inaccurate dose information for fast neutrons. This study sought to improve the accuracy in the dose estimation for fast neutrons by using two phantoms made of different materials in which the dose components can be separated according to differences in the interaction cross sections. The development of a “dual phantom technique” for measuring the fast neutron component of dose is reported. Methods: One phantom was filled with pure water. The other phantom was filled with a water solution of lithium hydroxide (LiOH) capitalizing on the absorbing characteristics of lithium-6 (Li-6) for thermal neutrons. Monte Carlo simulations were used to determine the ideal mixing ratio of Li-6 in LiOH solution. Changes in the depth dose distributions for each respective dose component along the central beam axis were used to assess the LiOH concentration at the 0, 0.001, 0.01, 0.1, 1, and 10 wt. % levels. Simulations were also performed with the phantom filled with 10 wt. % {sup 6}LiOH solution for 95%-enriched Li-6. A phantom was constructed containing 10 wt. % {sup 6}LiOH solution based on the simulation results. Experimental characterization of the

  3. Boron in sillimanite.

    Science.gov (United States)

    Grew, E S; Hinthorne, J R

    1983-08-05

    Sillimanite in six granulite-facies, kornerupine-bearing rocks contains 0.035 to 0.43 percent B(2)O(3) and 0.02 to 0.23 percent MgO (by weight). Substitution of boron for silicon and magnesium for aluminum is coupled such that the ratio of magnesium to boron is about 0.5. Sillimanite incorporates more than 0.1 percent B(2)O(3) only at high temperatures in a boron-rich environment at very low partial pressures of water. In the amphibolite facies, the sillimanite boron contents are too low to appreciably affect the stability relations of sillimanite with kyanite and andalusite.

  4. Combination of argan oil and phospholipids for the development of an effective liposome-like formulation able to improve skin hydration and allantoin dermal delivery.

    Science.gov (United States)

    Manca, Maria Letizia; Matricardi, Pietro; Cencetti, Claudia; Peris, Josè Esteban; Melis, Virginia; Carbone, Claudia; Escribano, Elvira; Zaru, Marco; Fadda, Anna Maria; Manconi, Maria

    2016-05-30

    Allantoin is traditionally employed in the treatment of skin ulcers and hypertrophic scars. In the present work, to improve its local deposition in the skin and deeper tissues, allantoin was incorporated in conventional liposomes and in new argan oil enriched liposomes. In both cases, obtained vesicles were unilamellar, as confirmed by cryo-TEM observation, but the addition of argan oil allowed a slight increase of the mean diameter (∼130nm versus ∼85nm). The formulations, especially those containing argan oil, favoured the allantoin accumulation in the skin, in particular in the dermis (∼8.7μg/cm(2)), and its permeation through the skin (∼33μg/cm(2)). The performances of vesicles as skin delivery systems were compared with those obtained by water dispersion of allantoin and the commercial gel, Sameplast(®). Moreover, in this work, for the first time, the elastic and viscous moduli of the skin were measured, underlining the different hydrating/moisturizing effects of the formulations. The application of ARG liposomes seems to provide a softening and relaxing effect on the skin, thus facilitating the drug accumulation and passage into and trough it.

  5. Multi-dimensional boron transport modeling in subchannel approach: Part II. Validation of CTF boron tracking model and adding boron precipitation model

    Energy Technology Data Exchange (ETDEWEB)

    Ozdemir, Ozkan Emre, E-mail: ozdemir@psu.edu; Avramova, Maria N., E-mail: mna109@psu.edu

    2014-10-15

    Highlights: • Validation of implemented multi-dimensional subchannel boron transport model. • Extension of boron transport model to entrained droplets. • Implementation of boron precipitation model. • Testing of the boron precipitation model under transient condition. - Abstract: The risk of small-break loss of coolant accident (SB-LOCA) and other reactivity initiated transients caused by boron dilution in the light water reactors (LWRs), and the complications of tracking the soluble boron concentration experimentally inside the primary coolant have stimulated the interest in computational studies for accurate boron tracking simulations in nuclear reactors. In Part I of this study, the development and implementation of a multi-dimensional boron transport model with modified Godunov scheme based on a subchannel approach within the COBRA-TF (CTF) thermal-hydraulic code was presented. The modified Godunov scheme approach with a physical diffusion term was determined to provide the most accurate and precise solution. Current paper extends these conclusions and presents the model validation studies against experimental data from the Rossendorf coolant mixing model (ROCOM) test facility. In addition, the importance of the two-phase flow characteristics in modeling boron transient are emphasized, especially during long-term cooling period after the loss of coolant accident (LOCA) condition in pressurized water reactors (PWRs). The CTF capabilities of boron transport modeling are further improved based on the three-field representation of the two-phase flow utilized in the code. The boron transport within entrained droplets is modeled, and a model for predicting the boron precipitation under transient conditions is developed and tested. It is aimed to extend the applicability of CTF to reactor transient simulations, and particularly to a large-break loss of coolant accident (LB-LOCA) analysis.

  6. Phospholipid liposomes functionalized by protein

    Science.gov (United States)

    Glukhova, O. E.; Savostyanov, G. V.; Grishina, O. A.

    2015-03-01

    Finding new ways to deliver neurotrophic drugs to the brain in newborns is one of the contemporary problems of medicine and pharmaceutical industry. Modern researches in this field indicate the promising prospects of supramolecular transport systems for targeted drug delivery to the brain which can overcome the blood-brain barrier (BBB). Thus, the solution of this problem is actual not only for medicine, but also for society as a whole because it determines the health of future generations. Phospholipid liposomes due to combination of lipo- and hydrophilic properties are considered as the main future objects in medicine for drug delivery through the BBB as well as increasing their bioavailability and toxicity. Liposomes functionalized by various proteins were used as transport systems for ease of liposomes use. Designing of modification oligosaccharide of liposomes surface is promising in the last decade because it enables the delivery of liposomes to specific receptor of human cells by selecting ligand and it is widely used in pharmacology for the treatment of several diseases. The purpose of this work is creation of a coarse-grained model of bilayer of phospholipid liposomes, functionalized by specific to the structural elements of the BBB proteins, as well as prediction of the most favorable orientation and position of the molecules in the generated complex by methods of molecular docking for the formation of the structure. Investigation of activity of the ligand molecule to protein receptor of human cells by the methods of molecular dynamics was carried out.

  7. Use of liposomal amphotericin B in bone marrow transplant.

    Directory of Open Access Journals (Sweden)

    Sastry P. S

    2005-01-01

    Full Text Available Increasing number of transplants worldwide has resulted in an increase in the incidence of fungal infections. Prolonged neutropenia, immunosuppression and graft vs. host disease all result in high predisposition to fungal infections. The likelihood of developing a fungal infection increases with the severity and duration of neutropenia, which, in the case of cancer or chemotherapy for the treatment of hematological malignancies, can range from a few days to several weeks. Invasive fungal infections are difficult to diagnose and neutropenic patients with fever often receive empirical antifungal therapy. This provides a rationale for the prophylactic use of antifungal agents. The empirical use of liposomal amphotericin B has overcome some of the difficulties usually found in this setting. The majority of clinical efficacy data related to liposomal amphotericin B are derived from compassionate use studies and case series. The major advantage of these liposomal formulations of amphotericin B is a reduction in amphotercin toxicity. Use of liposomal amphotericin has been shown to be a cost-effective approach abroad and the same has been our experience also. Commercially ambisome and Fungisome are the only products that contain true liposomes. Unlike ambisome, which needs to be used in dose of 3 mg/kg/day FungisomeTM is effective in the dose of 1-3 mg/kg bodyweight. The Indian liposomal preparation has shown to be safe and effective used in over 150 transplant patients in our experience. We conclude that the liposomal amphotericin is better-tolerated and also gives better responses in documented fungal infections.

  8. Boron Arsenide and Boron Phosphide for High Temperature and Luminescent Devices. [semiconductor devices - crystal growth/crystal structure

    Science.gov (United States)

    Chu, T. L.

    1975-01-01

    The crystal growth of boron arsenide and boron phosphide in the form of bulk crystals and epitaxial layers on suitable substrates is discussed. The physical, chemical, and electrical properties of the crystals and epitaxial layers are examined. Bulk crystals of boron arsenide were prepared by the chemical transport technique, and their carrier concentration and Hall mobility were measured. The growth of boron arsenide crystals from high temperature solutions was attempted without success. Bulk crystals of boron phosphide were also prepared by chemical transport and solution growth techniques. Techniques required for the fabrication of boron phosphide devices such as junction shaping, diffusion, and contact formation were investigated. Alloying techniques were developed for the formation of low-resistance ohmic contacts to boron phosphide. Four types of boron phosphide devices were fabricated: (1) metal-insulator-boron phosphide structures, (2) Schottky barriers; (3) boron phosphide-silicon carbide heterojunctions; and (4) p-n homojunctions. Easily visible red electroluminescence was observed from both epitaxial and solution grown p-n junctions.

  9. Exploring new labelling strategies for boronated compounds: towards fast development and efficient assessment of BNCT drug candidates

    OpenAIRE

    Gona, Kiran Babu

    2015-01-01

    208 p. La terapia por captura de neutrones (BNCT o Boron Neutron Capture Therapy), fue descrita por primera vez por Locher en 1936 y es una modalidad terapéutica binaria para el tratamiento del cáncer que se basa en la captura de neutrones térmicos por medio de átomos de 10B, previamente acumulados en las células tumorales. La captura del neutrón térmico resulta en la formación de un núcleo de 11B, que fisiona para generar dos iones altamente energéticos: 4He2+ y 7Li3+. El daño y la poster...

  10. Development of a novel neutron detection technique by using a boron layer coating a Charge Coupled Device

    CERN Document Server

    Blostein, Juan Jerónimo; Tartaglione, Aureliano; Haro, Miguel Sofo; Moroni, Guillermo Fernández; Cancelo, Gustavo

    2014-01-01

    This article describes the design features and the first test measurements obtained during the installation of a novel high resolution 2D neutron detection technique. The technique proposed in this work consists of a boron layer (enriched in ${^{10}}$B) placed on a scientific Charge Coupled Device (CCD). After the nuclear reaction ${^{10}}$B(n,$\\alpha$)${^{7}}$Li, the CCD detects the emitted charge particles thus obtaining information on the neutron absorption position. The above mentioned ionizing particles, with energies in the range 0.5-5.5 MeV, produce a plasma effect in the CCD which is recorded as a circular spot. This characteristic circular shape, as well as the relationship observed between the spot diameter and the charge collected, is used for the event recognition, allowing the discrimination of undesirable gamma events. We present the first results recently obtained with this technique, which has the potential to perform neutron tomography investigations with a spatial resolution better than that...

  11. Enhanced bactericidal potency of nanoliposomes by modification of the fusion activity between liposomes and bacterium

    Directory of Open Access Journals (Sweden)

    Ma YF

    2013-06-01

    Full Text Available Yufan Ma,1 Zhao Wang,1,2 Wen Zhao,1 Tingli Lu,1 Rutao Wang,1,2 Qibing Mei,1 Tao Chen1–3 1Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi, People's Republic of China; 2Shaanxi Liposome Research Center, Xi'an, Shaanxi, People's Republic of China; 3Xi'an Libang Pharmaceuticals Co, Ltd, Xi'an, People's Republic of China Background: Pseudomonas aeruginosa represents a good model of antibiotic resistance. These organisms have an outer membrane with a low level of permeability to drugs that is often combined with multidrug efflux pumps, enzymatic inactivation of the drug, or alteration of its molecular target. The acute and growing problem of antibiotic resistance of Pseudomonas to conventional antibiotics made it imperative to develop new liposome formulations to overcome these mechanisms, and investigate the fusion between liposome and bacterium. Methods: The rigidity, stability and charge properties of phospholipid vesicles were modified by varying the cholesterol, 1,2-dioleoyl-sn-glycero-3-phosphatidylethanolamine (DOPE, and negatively charged lipids 1,2-dimyristoyl-sn-glycero-3-phosphoglycerol sodium salt (DMPG, 1,2-dimyristoyl-sn-glycero-3-phopho-L-serine sodium salt (DMPS, 1,2-dimyristoyl-sn-glycero-3-phosphate monosodium salt (DMPA, nature phosphatidylserine sodium salt from brain and nature phosphatidylinositol sodium salt from soybean concentrations in liposomes. Liposomal fusion with intact bacteria was monitored using a lipid-mixing assay. Results: It was discovered that the fluid liposomes-bacterium fusion is not dependent on liposomal size and lamellarity. A similar degree of fusion was observed for liposomes with a particle size from 100 to 800 nm. The fluidity of liposomes is an essential pre-request for liposomes fusion with bacteria. Fusion was almost completely inhibited by incorporation of cholesterol into fluid liposomes. The increase in the

  12. Boron Rich Solids Sensors, Ultra High Temperature Ceramics, Thermoelectrics, Armor

    CERN Document Server

    Orlovskaya, Nina

    2011-01-01

    The objective of this book is to discuss the current status of research and development of boron-rich solids as sensors, ultra-high temperature ceramics, thermoelectrics, and armor. Novel biological and chemical sensors made of stiff and light-weight boron-rich solids are very exciting and efficient for applications in medical diagnoses, environmental surveillance and the detection of pathogen and biological/chemical terrorism agents. Ultra-high temperature ceramic composites exhibit excellent oxidation and corrosion resistance for hypersonic vehicle applications. Boron-rich solids are also promising candidates for high-temperature thermoelectric conversion. Armor is another very important application of boron-rich solids, since most of them exhibit very high hardness, which makes them perfect candidates with high resistance to ballistic impact. The following topical areas are presented: •boron-rich solids: science and technology; •synthesis and sintering strategies of boron rich solids; •microcantileve...

  13. Preparation and property analysis of a hepatocyte targeting pH-sensitive liposome

    Institute of Scientific and Technical Information of China (English)

    Si-Yuan Wen; Xiao-Hong Wang; Li Lin; Wei Guan; Sheng-Qi Wang

    2004-01-01

    AIM: To develop a hepatocyte targeting pH-sensitive liposome for drug delivery based on active targeting technology mediated by asialoglycoprotein receptors.METHODS: Four types of targeting molecules with galactose residue were synthesized and mixed with pH-sensitive lipids DC-chol/DOPE to prepare liposome with integrated property of hepatocyte specificity and pH sensitivity. Liposome 18-gal was selected with the best transfection activity through cellular uptake experiment. Property analysis was made through experiments of competitive inhibition of receptors,red blood cell hemolysis,in vitro cytotoxicity test by MTS assay and mediation of inhibitory effects of antisense phosphorothioate ODN on gene expression, etc.RESULTS: Liposome L8-gal had the desired properties of hepatocyte specificity, pH sensitivity, low cytotoxicity, and high transfection efficiency.CONCLUSION: Liposome 18-gal can be further developed as a potential hepatocyte- targeting delivery system.

  14. Development of an optical fiber type detector using a Eu:LiCaAlF{sub 6} scintillator for neutron monitoring in boron neutron capture therapy

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, Kenichi, E-mail: k-watanabe@nucl.nagoya-u.ac.jp [Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8603 (Japan); Kawabata, Yuya; Yamazaki, Atsushi; Uritani, Akira; Iguchi, Tetsuo [Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8603 (Japan); Fukuda, Kentaro [Tokuyama Corp., 1-1 Mikage-cho, Shunan-shi, Yamaguchi, 745-8648 (Japan); Yanagida, Takayuki [Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara, 630-0192 (Japan)

    2015-12-01

    We have developed a small neutron detector probe as a thermal neutron flux monitor for boron neutron capture therapy. The detector consists of an optical fiber and a small Eu:LiCaAlF{sub 6} scintillator. In order to improve neutron-gamma ray discrimination capability, we use the small-size scintillator, whose size is controlled to be smaller than fast electron range produced by gamma-rays and larger than the range of charged particles induced by {sup 6}Li(n,t) reactions. We confirmed the improved neutron-gamma ray discrimination capability by comparing the detector responses between a small-size scintillator and a slab one. We also evaluated the neutron sensitivity of the fabricated optical fiber type neutron detector to be 2×10{sup −4} cm{sup 2}.

  15. Development of particle induced gamma-ray emission methods for nondestructive determination of isotopic composition of boron and its total concentration in natural and enriched samples.

    Science.gov (United States)

    Chhillar, Sumit; Acharya, Raghunath; Sodaye, Suparna; Pujari, Pradeep K

    2014-11-18

    We report simple particle induced gamma-ray emission (PIGE) methods using a 4 MeV proton beam for simultaneous and nondestructive determination of the isotopic composition of boron ((10)B/(11)B atom ratio) and total boron concentrations in various solid samples with natural isotopic composition and enriched with (10)B. It involves measurement of prompt gamma-rays at 429, 718, and 2125 keV from (10)B(p,αγ)(7)Be, (10)B(p, p'γ)(10)B, and (11)B(p, p'γ)(11)B reactions, respectively. The isotopic composition of boron in natural and enriched samples was determined by comparing peak area ratios corresponding to (10)B and (11)B of samples to natural boric acid standard. An in situ current normalized PIGE method, using F or Al, was standardized for total B concentration determination. The methods were validated by analyzing stoichiometric boron compounds and applied to samples such as boron carbide, boric acid, carborane, and borosilicate glass. Isotopic compositions of boron in the range of 0.247-2.0 corresponding to (10)B in the range of 19.8-67.0 atom % and total B concentrations in the range of 5-78 wt % were determined. It has been demonstrated that PIGE offers a simple and alternate method for total boron as well as isotopic composition determination in boron based solid samples, including neutron absorbers that are important in nuclear technology.

  16. Innovative boron nitride-doped propellants

    Institute of Scientific and Technical Information of China (English)

    Thelma MANNING; Henry GRAU; Paul MATTER; Michael BEACHY; Christopher HOLT; Samuel SOPOK; Richard FIELD; Kenneth KLINGAMAN; Michael FAIR; John BOLOGNINI; Robin CROWNOVER; Carlton P. ADAM; Viral PANCHAL; Eugene ROZUMOV

    2016-01-01

    The U.S. military has a need for more powerful propellants with balanced/stoichiometric amounts of fuel and oxidants. However, balanced and more powerful propellants lead to accelerated gun barrel erosion and markedly shortened useful barrel life. Boron nitride (BN) is an interesting potential additive for propellants that could reduce gun wear effects in advanced propellants (US patent pending 2015-026P). Hexagonal boron nitride is a good lubricant that can provide wear resistance and lower flame temperatures for gun barrels. Further, boron can dope steel, which drastically improves its strength and wear resistance, and can block the formation of softer carbides. A scalable synthesis method for producing boron nitride nano-particles that can be readily dispersed into propellants has been developed. Even dispersion of the nano-particles in a double-base propellant has been demonstrated using a solvent-based processing approach. Stability of a composite propellant with the BN additive was verified. In this paper, results from propellant testing of boron nitride nano-composite propellants are presented, including closed bomb and wear and erosion testing. Detailed characterization of the erosion tester substrates before and after firing was obtained by electron microscopy, inductively coupled plasma and x-ray photoelectron spectroscopy. This promising boron nitride additive shows the ability to improve gun wear and erosion resistance without any destabilizing effects to the propellant. Potential applications could include less erosive propellants in propellant ammunition for large, medium and small diameter fire arms.

  17. Innovative boron nitride-doped propellants

    Directory of Open Access Journals (Sweden)

    Thelma Manning

    2016-04-01

    Full Text Available The U.S. military has a need for more powerful propellants with balanced/stoichiometric amounts of fuel and oxidants. However, balanced and more powerful propellants lead to accelerated gun barrel erosion and markedly shortened useful barrel life. Boron nitride (BN is an interesting potential additive for propellants that could reduce gun wear effects in advanced propellants (US patent pending 2015-026P. Hexagonal boron nitride is a good lubricant that can provide wear resistance and lower flame temperatures for gun barrels. Further, boron can dope steel, which drastically improves its strength and wear resistance, and can block the formation of softer carbides. A scalable synthesis method for producing boron nitride nano-particles that can be readily dispersed into propellants has been developed. Even dispersion of the nano-particles in a double-base propellant has been demonstrated using a solvent-based processing approach. Stability of a composite propellant with the BN additive was verified. In this paper, results from propellant testing of boron nitride nano-composite propellants are presented, including closed bomb and wear and erosion testing. Detailed characterization of the erosion tester substrates before and after firing was obtained by electron microscopy, inductively coupled plasma and x-ray photoelectron spectroscopy. This promising boron nitride additive shows the ability to improve gun wear and erosion resistance without any destabilizing effects to the propellant. Potential applications could include less erosive propellants in propellant ammunition for large, medium and small diameter fire arms.

  18. Doping Silicon Wafers with Boron by Use of Silicon Paste

    Institute of Scientific and Technical Information of China (English)

    Yu Gao; Shu Zhou; Yunfan Zhang; Chen Dong; Xiaodong Pi; Deren Yang

    2013-01-01

    In this work we introduce recently developed silicon-paste-enabled p-type doping for silicon.Boron-doped silicon nanoparticles are synthesized by a plasma approach.They are then dispersed in solvents to form silicon paste.Silicon paste is screen-printed at the surface of silicon wafers.By annealing,boron atoms in silicon paste diffuse into silicon wafers.Chemical analysis is employed to obtain the concentrations of boron in silicon nanoparticles.The successful doping of silicon wafers with boron is evidenced by secondary ion mass spectroscopy (SIMS) and sheet resistance measurements.

  19. In vivo and in vitro evaluation of octyl methoxycinnamate liposomes

    Directory of Open Access Journals (Sweden)

    de Carvalho Varjão Mota A

    2013-12-01

    Full Text Available Aline de Carvalho Varjão Mota,1 Zaida Maria Faria de Freitas,1 Eduardo Ricci Júnior,1 Gisela Maria Dellamora-Ortiz,1 Ralph Santos-Oliveira,2 Rafael Antonio Ozzetti,3 André Luiz Vergnanini,3 Vanessa Lira Ribeiro,4 Ronald Santos Silva,4 Elisabete Pereira dos Santos11Faculty of Pharmacy, Federal University of Rio de Janeiro, 2Nuclear Engineering Institute, National Nuclear Energy Commission, 3Allergisa Dermatocosmetic Research, University of Campinas, São Paulo, 4Pharmacology and Toxicology Department, National Insitute of Quality Control in Health, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilAbstract: Solar radiation causes damage to human skin, and photoprotection is the main way to prevent these harmful effects. The development of sunscreen formulations containing nanosystems is of great interest in the pharmaceutical and cosmetic industries because of the many potential benefits. This study aimed to develop and evaluate an octyl methoxycinnamate (OMC liposomal nanosystem (liposome/OMC to obtain a sunscreen formulation with improved safety and efficacy by retaining OMC for longer on the stratum corneum.Methods: The liposome/OMC nanostructure obtained was tested for enzymatic hydrolysis with lipase from Rhizomucor miehei and biodistribution with liposomes labeled with technetium-99m. The liposome/OMC formulation was then incorporated in a gel formulation and tested for ocular irritation using the hen’s egg test-chorio-allantoic membrane (HET-CAM assay, in vitro and in vivo sun protection factor, in vitro release profile, skin biometrics, and in vivo tape stripping.Results: The liposome/OMC nanosystem was not hydrolyzed from R. miehei by lipase. In the biodistribution assay, the liposome/OMC formulation labeled with technetium-99m had mainly deposited in the skin, while for OMC the main organ was the liver, showing that the liposome had higher affinity for the skin than OMC. The liposome/OMC formulation was classified as nonirritating in

  20. Translational siRNA therapeutics using liposomal carriers: prospects & challenges.

    Science.gov (United States)

    Bhavsar, Dhiraj; Subramanian, Krishnakumar; Sethuraman, Swaminathan; Krishnan, Uma Maheswari

    2012-08-01

    Gene silencing has emerged as a promising strategy for molecular therapy of various malignant, viral, hereditary and inflammatory disorders. However, its translation from lab to clinic is yet to gain momentum due to the numerous problems that plague its development. A multi-functional siRNA delivery system with desired properties such as enhanced immune compatibility, target specificity, high cell uptake and excellent silencing efficiency is required to understand the challenges involved in the selection and modification of small interfering RNA (siRNA), factors influencing the complexation process and the response of the biological system to the formulation. Liposomes have been used as delivery systems due to its versatility in handling different types of drugs, tunable size, charge and surface functionalities that improve its effectiveness in vivo. This review highlights the challenges involved in gene silencing and describes the progression of liposomal systems used in gene silencing. The rationale in introducing chemical modifications in siRNA, synthesizing designer cationic lipids and evolution of hybrid liposomal systems has been elaborated, emphasizing their merits and short-comings. Finally, a description of the current state of clinical trials involving liposomal formulations has been included to provide an unbiased perspective of the future of liposomal systems and gene silencing tools as therapeutic tools.

  1. Recognition of Biotin-functionalized Liposomes

    Institute of Scientific and Technical Information of China (English)

    Hai Feng ZHU; Jun Bai LI

    2003-01-01

    Functionalized liposomes were prepared by mixing the biotin in the lipid vesicle suspensions. The experiments through immersing streptavidin deposited mica into the biotin modified liposome solution testify the specifically biological binding interaction and extend the function of liposomes as a biosensor or drug carrier.

  2. Cardiac safety of liposomal anthracyclines.

    Science.gov (United States)

    Ewer, Michael S; Martin, Francis J; Henderson, Craig; Shapiro, Charles L; Benjamin, Robert S; Gabizon, Alberto A

    2004-12-01

    Conventional anthracyclines are active against many tumor types, but cardiotoxicity related to the cumulative dose may limit their use; this is particularly problematic for patients with risk factors for increased toxicity, for those who have received any anthracycline in the past, or for those who are to receive other cardiotoxic agents. Preclinical studies determined that encapsulating conventional anthracyclines in liposomes reduced the incidence and severity of cumulative dose-related cardiomyopathy while preserving antitumor activity. In controlled clinical trials, the risk of cardiotoxicity was significantly lower when nonpegylated liposomal doxorubicin (Myocet [NPLD]) was substituted for conventional doxorubicin, but the risk was not significantly different when NPLD was used in place of conventional epirubicin. Direct comparisons to conventional doxorubicin therapy showed comparable efficacy but significantly lower risk of cardiotoxicity with pegylated liposomal doxorubicin (Doxil/Caelyx [PLD]) therapy. Retrospective and prospective trials have not identified a maximum "cardiac safe" dose of PLD, despite use of cumulative doses exceeding 2,000 mg/m2 in some patients. Liposomal daunorubicin (DaunoXome [DNX]) may be associated with a lower risk of cardiotoxicity than conventional anthracyclines, but comparative trials are not available. With respect to combination chemotherapy, early results of clinical trials suggest that combining trastuzumab or a taxane with NPLD or PLD instead of a conventional anthracycline significantly reduces cardiotoxicity risk without reducing chemotherapeutic efficacy. Further results are eagerly awaited from ongoing controlled trials of cardiac safety with long-term liposomal anthracycline therapy, either alone or in combination with other potentially cardiotoxic agents.

  3. Boron-10 ABUNCL Active Testing

    Energy Technology Data Exchange (ETDEWEB)

    Kouzes, Richard T.; Ely, James H.; Lintereur, Azaree T.; Siciliano, Edward R.

    2013-07-09

    The Department of Energy Office of Nuclear Safeguards and Security (NA-241) is supporting the project Coincidence Counting With Boron-Based Alternative Neutron Detection Technology at Pacific Northwest National Laboratory (PNNL) for the development of a 3He proportional counter alternative neutron coincidence counter. The goal of this project is to design, build and demonstrate a system based upon 10B-lined proportional tubes in a configuration typical for 3He-based coincidence counter applications. This report provides results from testing of the active mode of the General Electric Reuter-Stokes Alternative Boron-Based Uranium Neutron Coincidence Collar (ABUNCL) at Los Alamos National Laboratory using sources and fuel pins.

  4. Magnetic nanoparticles for "smart liposomes".

    Science.gov (United States)

    Nakayama, Yoshitaka; Mustapić, Mislav; Ebrahimian, Haleh; Wagner, Pawel; Kim, Jung Ho; Hossain, Md Shahriar Al; Horvat, Joseph; Martinac, Boris

    2015-12-01

    Liposomal drug delivery systems (LDDSs) are promising tools used for the treatment of diseases where highly toxic pharmacological agents are administered. Currently, destabilising LDDSs by a specific stimulus at a target site remains a major challenge. The bacterial mechanosensitive channel of large conductance (MscL) presents an excellent candidate biomolecule that could be employed as a remotely controlled pore-forming nanovalve for triggered drug release from LDDSs. In this study, we developed superparamagnetic nanoparticles for activation of the MscL nanovalves by magnetic field. Synthesised CoFe2O4 nanoparticles with the radius less than 10 nm were labelled by SH groups for attachment to MscL. Activation of MscL by magnetic field with the nanoparticles attached was examined by the patch clamp technique showing that the number of activated channels under ramp pressure increased upon application of the magnetic field. In addition, we have not observed any cytotoxicity of the nanoparticles in human cultured cells. Our study suggests the possibility of using magnetic nanoparticles as a specific trigger for activation of MscL nanovalves for drug release in LDDSs.

  5. Novel mucus-penetrating liposomes as a potential oral drug delivery system: preparation, in vitro characterization, and enhanced cellular uptake

    Directory of Open Access Journals (Sweden)

    Li X

    2011-12-01

    Full Text Available Xiuying Li1, Dan Chen1, Chaoyi Le2, Chunliu Zhu1, Yong Gan1, Lars Hovgaard3, Mingshi Yang41Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China; 2University of Toronto Mississauga Campus, Ontario, Canada; 3Oral Formulation Development, Novo Nordisk A/S, Maalov; 4Department of Pharmaceutics and Analytical Chemistry, University of Copenhagen, Copenhagen, DenmarkBackground: The aim of this study was to investigate the intestinal mucus-penetrating properties and intestinal cellular uptake of two types of liposomes modified by Pluronic F127 (PF127.Methods: The two types of liposomes, ie, PF127-inlaid liposomes and PF127-adsorbed liposomes, were prepared by a thin-film hydration method followed by extrusion, in which coumarin 6 was loaded as a fluorescence marker. A modified Franz diffusion cell mounted with the intestinal mucus of rats was used to study the diffusion characteristics of the two types of PF127 liposomes. Cell uptake studies were conducted in Caco-2 cells and analyzed using confocal laser scanning microcopy as well as flow cytometry.Results: The diffusion efficiency of the two types of PF127-modified liposomes through intestinal rat mucus was 5–7-fold higher than that of unmodified liposomes. Compared with unmodified liposomes, PF127-inlaid liposomes showed significantly higher cellular uptake of courmarin 6. PF127-adsorbed liposomes showed a lower cellular uptake. Moreover, and interestingly, the two types of PF127-modified liposomes showed different cellular uptake mechanisms in Caco-2 cells.Conclusion: PF127-inlaid liposomes with improved intestinal mucus-penetrating ability and enhanced cellular uptake might be a potential carrier candidate for oral drug delivery.Keywords: Pluronic F127, mucus-penetrating, particles, liposomes, oral drug delivery

  6. Delivery of negatively charged liposomes into the atherosclerotic plaque of apolipoprotein E-deficient mouse aortic tissue.

    Science.gov (United States)

    Zhaorigetu, Siqin; Rodriguez-Aguayo, Cristian; Sood, Anil K; Lopez-Berestein, Gabriel; Walton, Brian L

    2014-09-01

    Liposomes have been used to diagnose and treat cancer and, to a lesser extent, cardiovascular disease. We previously showed the uptake of anionic liposomes into the atheromas of Watanabe heritable hyperlipidemic rabbits within lipid pools. However, the cellular distribution of anionic liposomes in atherosclerotic plaque remains undescribed. In addition, how anionic liposomes are absorbed into atherosclerotic plaque is unclear. We investigated the uptake and distribution of anionic liposomes in atherosclerotic plaque in aortic tissues from apolipoprotein E-deficient (ApoE(-/-)) mice. To facilitate the tracking of liposomes, we used liposomes containing fluorescently labeled non-silencing small interfering RNA. Confocal microscopy analysis showed the uptake of anionic liposomes into atherosclerotic plaque and colocalization with macrophages. Transmission electron microscopy analysis revealed anionic liposomal accumulation in macrophages. To investigate how anionic liposomes cross the local endothelial barrier, we examined the role of clathrin-mediated endocytosis in human coronary artery endothelial cells (HCAECs) treated with or without the inflammatory cytokine tumor necrosis factor (TNF)-α. Pretreatment with amantadine, an inhibitor of clathrin-mediated endocytosis, significantly decreased liposomal uptake in HCAECs treated with or without TNF-α by 77% and 46%, respectively. Immunoblot analysis showed that endogenous clathrin expression was significantly increased in HCAECs stimulated with TNF-α but was inhibited by amantadine. These studies indicated that clathrin-mediated endocytosis is partly responsible for the uptake of liposomes by endothelial cells. Our results suggest that anionic liposomes target macrophage-rich areas of vulnerable plaque in ApoE(-)(/)(-) mice; this finding may lead to the development of novel diagnostic and therapeutic strategies for treating vulnerable plaque in humans.

  7. Boron and the kidney.

    Science.gov (United States)

    Pahl, Madeleine V; Culver, B Dwight; Vaziri, Nosratola D

    2005-10-01

    Boron, the fifth element in the periodic table, is ubiquitous in nature. It is present in food and in surface and ocean waters, and is frequently used in industrial, cosmetic, and medical settings. Exposure to boron and related compounds has been recently implicated as a potential cause of chronic kidney disease in Southeast Asia. This observation prompted the present review of the published data on the effects of acute and chronic exposure to boron on renal function and structure in human beings and in experimental animals.

  8. Efficacy and safety of liposomal anthracyclines in phase I/II clinical trials.

    Science.gov (United States)

    Alberts, David S; Muggia, Franco M; Carmichael, James; Winer, Eric P; Jahanzeb, Mohammad; Venook, Alan P; Skubitz, Keith M; Rivera, Edgardo; Sparano, Joseph A; DiBella, Nicholas J; Stewart, Simon J; Kavanagh, John J; Gabizon, Alberto A

    2004-12-01

    Preclinical studies have established the pharmacologic advantages of liposomal anthracyclines, including pharmacokinetic profiles after bolus dosing that resemble continuous infusion of conventional anthracyclines, increased drug concentrations in tumor cells compared with the surrounding tissues, and reduced toxicity relative to conventional anthracycline treatment. Based on these studies, many phase I and phase II clinical trials were conducted to assess the safety and potential activity of liposomal anthracyclines in the management of both solid and hematologic tumors. These studies provided valuable insight into the safety of pegylated liposomal doxorubicin (Doxil/Caelyx [PLD]), nonpegylated liposomal doxorubicin (Myocet [NPLD]), and liposomal daunorubicin (DaunoXome [DNX]) over a range of doses, either as single-agent therapy or in combination with other cytotoxic agents. Other liposomal anthracyclines in development may be well tolerated but their activity remains to be elucidated by clinical trials. The available data also suggest that liposomal anthracyclines have activity not only against tumor types with known sensitivity to conventional anthracyclines, but also potentially for tumors that are typically anthracycline-resistant. Despite the availability of clinical data from a wide variety of tumor types and patient populations, further studies of liposomal anthracycline therapy are needed to fully establish their safety, efficacy, and dosing in the treatment of these patients.

  9. Relationship between the adjuvant and cytotoxic effects of the positive charges and polymerization in liposomes.

    Science.gov (United States)

    Gasparri, Julieta; Speroni, Lucía; Chiaramoni, Nadia Silvia; del Valle Alonso, Silvia

    2011-06-01

    Vaccine development today encounters a main obstacle, which is the need for effective adjuvants suitable for clinical trials. Aluminum salts, discovered 70 years ago and, very recently, MF59, are the only types of adjuvants currently used in vaccines licensed by the U.S. Food and Drug Administration. Liposomes represent an alternative approach to vaccine adjuvants. In this article, we describe the inflammatory response and biological effect of polymerization and the addition of positive charges in liposome formulations. Nonpolymerized cationic (NP(+)) liposomes significantly reduce metabolism in Vero cells after 24 hours. Correspondingly, both NP(+) and polymerized cationic (P(+)) liposomes reduce cell viability following a 48-hour incubation. Similar results were obtained with cells from the peritoneal cavities of mice. Paradoxically, those liposomes that presented clearly cytostatic or cytotoxic effects in vitro stimulated metabolism and had a mitogenic effect in vivo. Finally, the adjuvant effect was tested by immunization in BALB/c mice. The major effect was obtained with NP(+) liposomes. Accordingly, we also demonstrated that NP(+) liposomes injected into the dermis produced an outstanding inflammatory reaction, showing the histopathological characteristics of an inoculation granuloma. Thus, positive charge would play an important role in the immunoadjuvant effect of liposomes by conferring them cytotoxic capacity.

  10. Use of a passive equilibration methodology to encapsulate cisplatin into preformed thermosensitive liposomes.

    Science.gov (United States)

    Woo, Janet; Chiu, Gigi N C; Karlsson, Göran; Wasan, Ellen; Ickenstein, Ludger; Edwards, Katarina; Bally, Marcel B

    2008-02-12

    A conventional, cholesterol-containing liposome formulation of cisplatin has demonstrated insignificant activity in clinical trials, due in part, to insufficient release of encapsulated content following localization within solid tumors. For this reason, the development of a triggered release liposome formulation is desirable. In this report, cisplatin was encapsulated into lysolipid-containing thermosensitive liposomes (LTSL) using a novel technique, which relies on the equilibration of cisplatin across the liposomal membrane at temperatures above the gel-to-liquid crystalline phase transition temperature (TC) of the bulk phospholipid. Mild heating and drug loading into LTSL did not induce morphological changes of the liposomes. In vitro data demonstrated that >95% of encapsulated cisplatin was released from LTSL within 5 min following mild heating at 42 degrees C, while liposomes exhibited 70% release of cisplatin at 42 degrees C, and cholesterol-containing liposomes exhibited negligible drug release at 42 degrees C. The pharmacokinetic profiles of LTSL- and TSL-cisplatin indicated that these formulations were rapidly eliminated from circulation (terminal t(1/2) of 1.09 and 2.83 h, respectively). The therapeutic utility of LTSL-cisplatin formulation will be based on strategies where hyperthermia is applied prior to the administration of the liposomal drug-a strategy similar to that used in the clinical assessment of LTSL-doxorubicin formulation.

  11. Liposomal encapsulation of the natural flavonoid fisetin improves bioavailability and antitumor efficacy.

    Science.gov (United States)

    Seguin, Johanne; Brullé, Laura; Boyer, Renaud; Lu, Yen Mei; Ramos Romano, Miriam; Touil, Yasmine S; Scherman, Daniel; Bessodes, Michel; Mignet, Nathalie; Chabot, Guy G

    2013-02-28

    The natural flavonoid fisetin (3,3',4',7-tetrahydroxyflavone) has shown antiangiogenic and anticancer properties. Because of fisetin limited water solubility, we designed a liposomal formulation and evaluated its biological properties in vitro and in Lewis lung carcinoma (LLC) bearing mice. A liposomal formulation was developed with DOPC and DODA-PEG2000, possessing a diameter in the nanometer range (173.5±2.4nm), a high homogeneity (polydispersity index 0.181±0.016) and high fisetin encapsulation (58%). Liposomal fisetin incubated with LLC cells were internalized, induced a typical fisetin morphological effect and increased the sub-G1 cell distribution. In vivo, liposomal fisetin allowed a 47-fold increase in relative bioavailability compared to free fisetin. The effect of liposomal fisetin on LLC tumor growth in mice at low dose (21mg/kg) allowed a higher tumor growth delay (3.3 days) compared to free fisetin at the same dose (1.6 day). Optimization of liposomal fisetin therapy was attempted by co-treatment with cyclophosphamide which led to a significant improvement in tumor growth delay (7.2 days) compared to cyclophosphamide with control liposomes (4.2 days). In conclusion, fisetin liposomes markedly improved fisetin bioavailability and anticancer efficacy in mice and this formulation could facilitate the administration of this flavonoid in the clinical setting.

  12. Innovative method for boron extraction from iron ore containing boron

    Science.gov (United States)

    Wang, Guang; Wang, Jing-song; Yu, Xin-yun; Shen, Ying-feng; Zuo, Hai-bin; Xue, Qing-guo

    2016-03-01

    A novel process for boron enrichment and extraction from ludwigite based on iron nugget technology was proposed. The key steps of this novel process, which include boron and iron separation, crystallization of boron-rich slag, and elucidation of the boron extraction behavior of boron-rich slag by acid leaching, were performed at the laboratory. The results indicated that 95.7% of the total boron could be enriched into the slag phase, thereby forming a boron-rich slag during the iron and slag melting separation process. Suanite and kotoite were observed to be the boron-containing crystalline phases, and the boron extraction properties of the boron-rich slag depended on the amounts and grain sizes of these minerals. When the boron-rich slag was slowly cooled to 1100°C, the slag crystallized well and the efficiency of extraction of boron (EEB) of the slag was the highest observed in the present study. The boron extraction property of the slow-cooled boron-rich slag obtained in this study was much better than that of szaibelyite ore under the conditions of 80% of theoretical sulfuric acid amount, leaching time of 30 min, leaching temperature of 40°C, and liquid-to-solid ratio of 8 mL/g.

  13. Cancer Immunotherapy Utilized Bubble Liposomes and Ultrasound as Antigen Delivery System

    Science.gov (United States)

    Oda, Yusuke; Otake, Shota; Suzuki, Ryo; Otake, Shota; Nishiie, Norihito; Hirata, Keiichi; Taira, Yuichiro; Utoguchi, Naoki; Maruyama, Kazuo

    2010-03-01

    In dendritic cells (DCs)-based cancer immunotherapy, it is important to present the epitope peptide derived from tumor associated antigens (TAAs) on MHC class I in order to induce tumor specific cytotoxic T lymphocytes (CTLs). However, MHC class I molecules generally present the epitope peptides derived from endogenous antigens for DCs but not exogenous ones such as TAAs. Recently, we developed the novel liposomal bubbles (Bubble liposomes) encapsulating perfluoropropane nanobubbles. In this study, we attempted to establish the novel antigen delivery system to induce MHC class I presentation using the combination of ultrasound and Bubble liposomes. Using ovalbumin (OVA) as model antigen, the combination of Bubble liposomes and ultrasound exposure for the DC could induce MHC class I presentation. In addition, the viability of DCs was more than 80%. These results suggest that Bubble liposomes might be a novel ultrasound enhanced antigen delivery tool in DC-based cancer immunotherapy.

  14. Recent Trends in Multifunctional Liposomal Nanocarriers for Enhanced Tumor Targeting

    Directory of Open Access Journals (Sweden)

    Federico Perche

    2013-01-01

    Full Text Available Liposomes are delivery systems that have been used to formulate a vast variety of therapeutic and imaging agents for the past several decades. They have significant advantages over their free forms in terms of pharmacokinetics, sensitivity for cancer diagnosis and therapeutic efficacy. The multifactorial nature of cancer and the complex physiology of the tumor microenvironment require the development of multifunctional nanocarriers. Multifunctional liposomal nanocarriers should combine long blood circulation to improve pharmacokinetics of the loaded agent and selective distribution to the tumor lesion relative to healthy tissues, remote-controlled or tumor stimuli-sensitive extravasation from blood at the tumor’s vicinity, internalization motifs to move from tumor bounds and/or tumor intercellular space to the cytoplasm of cancer cells for effective tumor cell killing. This review will focus on current strategies used for cancer detection and therapy using liposomes with special attention to combination therapies.

  15. Development of a novel neutron detection technique by using a boron layer coating a Charge Coupled Device

    Energy Technology Data Exchange (ETDEWEB)

    Blostein, Juan Jerónimo; Estrada, Juan; Tartaglione, Aureliano; Sofo haro, Miguel; Fernández Moroni, Guillermo; Cancelo, Gustavo

    2015-01-19

    This article describes the design features and the first test measurements obtained during the installation of a novel high resolution 2D neutron detection technique. The technique proposed in this work consists of a boron layer (enriched in ${^{10}}$B) placed on a scientific Charge Coupled Device (CCD). After the nuclear reaction ${^{10}}$B(n,$\\alpha$)${^{7}}$Li, the CCD detects the emitted charge particles thus obtaining information on the neutron absorption position. The above mentioned ionizing particles, with energies in the range 0.5-5.5 MeV, produce a plasma effect in the CCD which is recorded as a circular spot. This characteristic circular shape, as well as the relationship observed between the spot diameter and the charge collected, is used for the event recognition, allowing the discrimination of undesirable gamma events. We present the first results recently obtained with this technique, which has the potential to perform neutron tomography investigations with a spatial resolution better than that previously achieved. Numerical simulations indicate that the spatial resolution of this technique will be about 15 $\\mu$m, and the intrinsic detection efficiency for thermal neutrons will be about 3 %. We compare the proposed technique with other neutron detection techniques and analyze its advantages and disadvantages.

  16. Thermosensitive liposomal drug delivery systems: state of the art review

    Directory of Open Access Journals (Sweden)

    Kneidl B

    2014-09-01

    Full Text Available Barbara Kneidl,1,2 Michael Peller,3 Gerhard Winter,2 Lars H Lindner,1 Martin Hossann11Department of Internal Medicine III, University Hospital Munich, 2Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, 3Institute for Clinical Radiology, University Hospital Munich, Ludwig-Maximilians University, Munich, GermanyAbstract: Thermosensitive liposomes are a promising tool for external targeting of drugs to solid tumors when used in combination with local hyperthermia or high intensity focused ultrasound. In vivo results have demonstrated strong evidence that external targeting is superior over passive targeting achieved by highly stable long-circulating drug formulations like PEGylated liposomal doxorubicin. Up to March 2014, the Web of Science listed 371 original papers in this field, with 45 in 2013 alone. Several formulations have been developed since 1978, with lysolipid-containing, low temperature-sensitive liposomes currently under clinical investigation. This review summarizes the historical development and effects of particular phospholipids and surfactants on the biophysical properties and in vivo efficacy of thermosensitive liposome formulations. Further, treatment strategies for solid tumors are discussed. Here we focus on temperature-triggered intravascular and interstitial drug release. Drug delivery guided by magnetic resonance imaging further adds the possibility of performing online monitoring of a heating focus to calculate locally released drug concentrations and to externally control drug release by steering the heating volume and power. The combination of external targeting with thermosensitive liposomes and magnetic resonance-guided drug delivery will be the unique characteristic of this nanotechnology approach in medicine.Keywords: thermosensitive liposomes, phosphatidyloligoglycerol, hyperthermia, high intensity focused ultrasound, drug delivery, drug targeting

  17. Delivery of aerosolized drugs encapsulated in liposomes

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Yung-Sung; Lyons, C.R. [Univ. of New Mexico, Albuquerque, NM (United States); Schmid, M.H.

    1995-12-01

    Mycobacterium tuberculosis (Mtb) is an infectious disease that resides in the human lung. Due to the difficulty in completely killing off the disease in infected individuals, Mtb has developed drug-resistant forms and is on the rise in the human population. Therefore, ITRI and the University of New Mexico are collaborating to explore the treatment of Mtb by an aerosolized drug delivered directly to the lungs. In conclusion, it is feasible to obtain an appropriate size and concentration of the liposomes before and after aerosolization.

  18. Selective Delivery of an Anticancer Drug with Aptamer-Functionalized Liposomes to Breast Cancer Cells in Vitro and in Vivo.

    Science.gov (United States)

    Xing, Hang; Tang, Li; Yang, Xujuan; Hwang, Kevin; Wang, Wendan; Yin, Qian; Wong, Ngo Yin; Dobrucki, Lawrence W; Yasui, Norio; Katzenellenbogen, John A; Helferich, William G; Cheng, Jianjun; Lu, Yi

    2013-10-21

    Selective targeting of cancer cells is a critical step in cancer diagnosis and therapy. To address this need, DNA aptamers have attracted significant attention as possible targeting ligands. However, while their use in targeting cancer cells in vitro has been reported, their effectiveness has rarely been established in vivo. Here we report the development of a liposomal drug delivery system for targeted anticancer chemotherapy. Liposomes were prepared containing doxorubicin as a payload, and functionalized with AS1411, a DNA aptamer with strong binding affinity for nucleolin. AS1411 aptamer-functionalized liposomes increased cellular internalization and cytotoxicity to MCF-7 breast cancer cells as compared to non-targeting liposomes. Furthermore, targeted liposomal doxorubicin improved antitumor efficacy against xenograft MCF-7 breast tumors in athymic nude mice, attributable to their enhanced tumor tissue penetration. This study suggests that AS1411 aptamer-functionalized liposomes can recognize nucleolin overexpressed on MCF-7 cell surface, and therefore enable drug delivery with high specificity and selectivity.

  19. Boron nitride composites

    Science.gov (United States)

    Kuntz, Joshua D.; Ellsworth, German F.; Swenson, Fritz J.; Allen, Patrick G.

    2016-02-16

    According to one embodiment, a composite product includes hexagonal boron nitride (hBN), and a plurality of cubic boron nitride (cBN) particles, wherein the plurality of cBN particles are dispersed in a matrix of the hBN. According to another embodiment, a composite product includes a plurality of cBN particles, and one or more borate-containing binders.

  20. Surface functionalization of liposomes with proteins and carbohydrates for use in anti-cancer applications

    Science.gov (United States)

    Platt, Virginia M.

    Kate for NTA occupancy. In the circulation of mice, his-tagged proteins associated with NTA-liposomes were cleared as rapidly as free protein. In Chapter 4, I study the effect of NTA/his-tag avidity on immune response when NTA-containing liposomes are used as non-covalent, particulate adjuvants. Two his-tagged antigens, ovalbumin and the membrane proximal portion of HIV Gag, were associated with NTA-liposomes containing either mono-NTA or tris-NTA lipids. The immune response to each antigen was compared to control adjuvant formulations in which antigens were admixed with or covalently-conjugated to liposomes. The weaker antigen, the HIV Gag peptide, induced a stronger immune response when associated with NTA-containing liposomes than when admixed with liposomes. Ovalbumin preparations in which the protein was admixed with particles or non-covalently associated with NTA-liposomes elicited a higher immune response than free ovalbumin or ovalbumin admixed with the control adjuvant alum. For both antigens, NTA-liposome responses were less than the response to antigens covalently linked to the liposome. In Chapter 5, I evaluate the potential for hyaluronidase to target conjugated liposomes to tumors or improve liposome motility within hyaluronan-rich tumors. Ovine hyaluronidase was modified using iminothiolane to introduce sulfhydryl groups into the enzyme. The enzyme was attached to liposomes via maleimide lipids or to maleimidehis10 in order to engineer non-covalent NTA-liposome association. Enzyme activity was retained after sulfhydryl addition and after attachment to liposomes. Liposome-conjugated hyaluronidase degraded an HA-gel at the same rate as admixed liposomes. When hyaluronidase-liposomes were injected intravenously in mice, the hyaluronidase conjugated-liposomes experienced faster clearance than control liposomes but slower clearance than free hyaluronidase. As a whole, these studies may help develop universal methods for a range of protein therapeutics and anti

  1. Effective mucoadhesive liposomal delivery system for risedronate: preparation and in vitro/in vivo characterization

    Directory of Open Access Journals (Sweden)

    Jung IW

    2014-05-01

    Full Text Available Il-Woo Jung, Hyo-Kyung HanCollege of Pharmacy, Dongguk University-Seoul, Ilsan-Donggu, Goyang, Republic of KoreaAbstract: In this work, we aimed to develop chitosan-coated mucoadhesive liposomes ­containing risedronate to improve intestinal drug absorption. Liposomes containing risedronate were prepared with 1,2-distearoryl-sn-glycero-3-phosphocholine and distearoryl-sn-glycero-3-[phospho-rac-(1-glycerol] using the freeze-drying method, with subsequent coating of the anionic surfaces of the liposomes with chitosan. The in vitro characteristics of the chitosan-coated liposomes were investigated, including their stability, mucoadhesiveness, and Caco-2 cell permeability. This formulation was stable in simulated gastric and intestinal fluids, with the percentage of drug remaining in the liposomes being more than 90% after 24 hours of incubation. Chitosan-coated liposomes also showed strong mucoadhesive properties, implying potential electrostatic interaction with the mucous layer in the gastrointestinal tract. Compared with the untreated drug, chitosan-coated liposomes significantly enhanced the cellular uptake of risedronate, resulting in an approximately 2.1–2.6-fold increase in Caco-2 cells. Further, the chitosan-coated liposomes increased the oral exposure of risedronate by three-fold in rats. Taken together, the results of this study suggest that chitosan-coated liposomes containing risedronate should be effective for improving the bioavailability of risedronate.Keywords: cellular uptake, bioavailability, mucoadhesiveness, liposome, chitosan

  2. The use of liposomal anthracycline analogues for childhood malignancies: A systematic review.

    Science.gov (United States)

    Sieswerda, E; Kremer, L C M; Caron, H N; van Dalen, E C

    2011-09-01

    In an effort to prevent or reduce anthracycline-induced cardiotoxicity, liposomal anthracyclines have been developed. The objective of this systematic review was to summarise all available evidence on the benefits and risks of liposomal anthracyclines in children with cancer. We searched databases (MEDLINE (1966-September 2009), EMBASE (1980-September 2009) and CENTRAL (The Cochrane Library, issue 3 2009)), reference lists of relevant articles and ongoing trial databases for relevant studies. Two reviewers independently performed study selection, data extraction and quality assessment of included studies. No randomised controlled trials (RCTs) or controlled clinical trials (CCTs) were found. Fifteen observational studies described the use of liposomal anthracyclines in children with cancer. Most patients had been treated extensively in the past. Some patients developed cardiotoxicity, serious allergic reactions, mucositis, infections, hematotoxicities and/or hepatotoxicity after single agent treatment. However, due to the low quality of the currently available research, it is unclear what the exact risks are. In conclusion, there is no evidence available from RCTs or CCTs about the benefits and risks of liposomal anthracyclines in children with cancer. Limited data from observational studies suggest that children treated with liposomal anthracyclines are at risk for developing cardiotoxicity and other serious toxicities. There is an urgent need for results of well-designed studies which accurately evaluate the benefits and risks of liposomal anthracyclines in children with cancer. Until high quality evidence is available, we recommend monitoring of cardiac function in childhood cancer patients treated with a liposomal anthracycline and awareness of other serious toxicities.

  3. Liposomal bupivacaine and clinical outcomes.

    Science.gov (United States)

    Tong, Yi Cai Isaac; Kaye, Alan David; Urman, Richard D

    2014-03-01

    In the multimodal approach to the management of postoperative pain, local infiltration and regional blocks have been increasingly utilized for pain control. One of the limitations of local anesthetics in the postoperative setting is its relatively short duration of action. Multivesicular liposomes containing bupivacaine have been increasingly utilized for their increased duration of action. Compared with bupivacaine HCl, local infiltration of liposomal bupivacaine has shown to have an increase in duration of action and causes delay in peak plasma concentration. In this article, we attempt to review the clinical literature surrounding liposomal bupivacaine and its evolving role in perioperative analgesia. This new bupivacaine formation may have promising implications in postoperative pain control, resulting in increased patient satisfaction and a decrease in both hospital stay and opioid-induced adverse events (AEs). Although more studies are needed, the preliminary clinical trials suggest that liposomal bupivacaine has predictable pharmacokinetics, a similar side effect profile compared with bupivacaine HCl, and is effective in providing increased postoperative pain control.

  4. 64Cu loaded liposomes as positron emission tomography imaging agents

    DEFF Research Database (Denmark)

    Petersen, Anncatrine Luisa; Binderup, Tina; Rasmussen, Palle;

    2011-01-01

    We have developed a highly efficient method for utilizing liposomes as imaging agents for positron emission tomography (PET) giving high resolution images and allowing direct quantification of tissue distribution and blood clearance. Our approach is based on remote loading of a copper-radionuclid...

  5. Soft Interaction in Liposome Nanocarriers for Therapeutic Drug Delivery

    Directory of Open Access Journals (Sweden)

    Domenico Lombardo

    2016-06-01

    Full Text Available The development of smart nanocarriers for the delivery of therapeutic drugs has experienced considerable expansion in recent decades, with the development of new medicines devoted to cancer treatment. In this respect a wide range of strategies can be developed by employing liposome nanocarriers with desired physico-chemical properties that, by exploiting a combination of a number of suitable soft interactions, can facilitate the transit through the biological barriers from the point of administration up to the site of drug action. As a result, the materials engineer has generated through the bottom up approach a variety of supramolecular nanocarriers for the encapsulation and controlled delivery of therapeutics which have revealed beneficial developments for stabilizing drug compounds, overcoming impediments to cellular and tissue uptake, and improving biodistribution of therapeutic compounds to target sites. Herein we present recent advances in liposome drug delivery by analyzing the main structural features of liposome nanocarriers which strongly influence their interaction in solution. More specifically, we will focus on the analysis of the relevant soft interactions involved in drug delivery processes which are responsible of main behaviour of soft nanocarriers in complex physiological fluids. Investigation of the interaction between liposomes at the molecular level can be considered an important platform for the modeling of the molecular recognition processes occurring between cells. Some relevant strategies to overcome the biological barriers during the drug delivery of the nanocarriers are presented which outline the main structure-properties relationships as well as their advantages (and drawbacks in therapeutic and biomedical applications.

  6. Metallomics in drug development

    DEFF Research Database (Denmark)

    Nguyen, Trinh Thi Nhu Tam; Ostergaard, Jesper; Stürup, Stefan;

    2013-01-01

    A capillary electrophoresis inductively coupled plasma mass spectrometry method for separation of free cisplatin from liposome-encapsulated cisplatin and protein-bound cisplatin was developed. A liposomal formulation of cisplatin based on PEGylated liposomes was used as model drug formulation...... to plasma constituents in plasma samples. It was demonstrated that this approach is suitable for studies of the stability of liposome formulations as leakage of active drug from the liposomes and subsequent binding to biomolecules in plasma can be monitored. This methodology has not been reported before...... and will improve characterization of liposomal drugs during drug development and in studies on kinetics....

  7. Improved oral bioavailability of capsaicin via liposomal nanoformulation: preparation, in vitro drug release and pharmacokinetics in rats.

    Science.gov (United States)

    Zhu, Yuan; Wang, Miaomiao; Zhang, Jiajia; Peng, Wei; Firempong, Caleb Kesse; Deng, Wenwen; Wang, Qilong; Wang, Shicheng; Shi, Feng; Yu, Jiangnan; Xu, Ximing; Zhang, Weiming

    2015-04-01

    This study innovatively prepared an effective capsaicin-loaded liposome, a nanoformulation with fewer irritants, for oral administration. The in vitro and in vivo properties of the liposomal encapsulation were investigated and the potential possibility of oral administration evaluated. The liposomal agent composed of phospholipid, cholesterol, sodium cholate and isopropyl myristate was prepared using film-dispersion method. A level A in vitro-in vivo correlation (IVIVC) was established for the first time, which demonstrated an excellent IVIVC of both formulated and free capsaicin in oral administration. Physicochemical characterizations including mean particle size, zeta (ζ) potential and average encapsulation efficiency of capsaicin-loaded liposome were found to be 52.2 ± 1.3 nm, -41.5 ± 2.71 mv and 81.9 ± 2.43 %, respectively. In vivo, liposomal encapsulation allowed a 3.34-fold increase in relative bioavailability compared to free capsaicin. The gastric mucosa irritation studies indicated that the liposomal system was a safe carrier for oral administration. These results support the fact that capsaicin, an effective drug for the treatment of neuropathic pain, could be encapsulated in liposome for improved oral bioavailability. The excellent IVIVC of capsaicin-loaded liposome could also be a promising tool in liposomal formulation development with an added advantage of reduced animal testing.

  8. The potential of liposome-encapsulated ciprofloxacin as a tularemia therapy.

    Science.gov (United States)

    Hamblin, Karleigh A; Wong, Jonathan P; Blanchard, James D; Atkins, Helen S

    2014-01-01

    Liposome-encapsulation has been suggested as method to improve the efficacy of ciprofloxacin against the intracellular pathogen, Francisella tularensis. Early work with a prototype formulation, evaluated for use against the F. tularensis live vaccine strain, showed that a single dose of liposomal ciprofloxacin given by the intranasal or inhalational route could provide protection in a mouse model of pneumonic tularemia. Liposomal ciprofloxacin offered better protection than ciprofloxacin given by the same routes. Liposomal ciprofloxacin has been further developed by Aradigm Corporation for Pseudomonas aeruginosa infections in patients with cystic fibrosis and non-cystic fibrosis bronchiectasis. This advanced development formulation is safe, effective and well tolerated in human clinical trials. Further evaluation of the advanced liposomal ciprofloxacin formulation against the highly virulent F. tularensis Schu S4 strain has shown that aerosolized CFI (Ciprofloxacin encapsulated in liposomes for inhalation) provides significantly better protection than oral ciprofloxacin. Thus, liposomal ciprofloxacin is a promising treatment for tularemia and further research with the aim of enabling licensure under the animal rule is warranted.

  9. Pollen Morphology and Boron Concentration in Floral Tissues as Factors Triggering Natural and GA-Induced Parthenocarpic Fruit Development in Grapevine

    Science.gov (United States)

    Pérez-Díaz, Ricardo; Yáñez, Mónica; Tapia, Jaime; Moreno, Yerko

    2015-01-01

    Parthenocarpic fruit development (PFD) reduces fruit yield and quality in grapevine. Parthenocarpic seedless berries arise from fruit set without effective fertilization due to defective pollen germination. PFD has been associated to micronutrient deficiency but the relation of this phenomenon with pollen polymorphism has not been reported before. In this work, six grapevine cultivars with different tendency for PFD and grown under micronutrient-sufficient conditions were analyzed to determine pollen structure and germination capability as well as PFD rates. Wide variation in non-germinative abnormal pollen was detected either among cultivars as well as for the same cultivar in different growing seasons. A straight correlation with PFD rates was found (R2 = 0.9896), suggesting that natural parthenocarpy is related to defective pollen development. Such relation was not observed when PFD was analyzed in grapevine plants exposed to exogenous gibberellin (GA) or abscissic acid (ABA) applications at pre-anthesis. Increase (GA treatment) or reduction (ABA treatment) in PFD rates without significative changes in abnormal pollen was determined. Although these plants were maintained at sufficient boron (B) condition, a down-regulation of the floral genes VvBOR3 and VvBOR4 together with a reduction of floral B content in GA-treated plants was established. These results suggest that impairment in B mobility to reproductive tissues and restriction of pollen tube growth could be involved in the GA-induced parthenocarpy. PMID:26440413

  10. Transport of Boron by the tassel-less1 Aquaporin Is Critical for Vegetative and Reproductive Development in Maize[C][W][OPEN

    Science.gov (United States)

    Durbak, Amanda R.; Phillips, Kimberly A.; Pike, Sharon; O’Neill, Malcolm A.; Mares, Jonathan; Gallavotti, Andrea; Malcomber, Simon T.; Gassmann, Walter; McSteen, Paula

    2014-01-01

    The element boron (B) is an essential plant micronutrient, and B deficiency results in significant crop losses worldwide. The maize (Zea mays) tassel-less1 (tls1) mutant has defects in vegetative and inflorescence development, comparable to the effects of B deficiency. Positional cloning revealed that tls1 encodes a protein in the aquaporin family co-orthologous to known B channel proteins in other species. Transport assays show that the TLS1 protein facilitates the movement of B and water into Xenopus laevis oocytes. B content is reduced in tls1 mutants, and application of B rescues the mutant phenotype, indicating that the TLS1 protein facilitates the movement of B in planta. B is required to cross-link the pectic polysaccharide rhamnogalacturonan II (RG-II) in the cell wall, and the percentage of RG-II dimers is reduced in tls1 inflorescences, indicating that the defects may result from altered cell wall properties. Plants heterozygous for both tls1 and rotten ear (rte), the proposed B efflux transporter, exhibit a dosage-dependent defect in inflorescence development under B-limited conditions, indicating that both TLS1 and RTE function in the same biological processes. Together, our data provide evidence that TLS1 is a B transport facilitator in maize, highlighting the importance of B homeostasis in meristem function. PMID:25035406

  11. A Rigorous Theory of Remote Loading of Drugs into Liposomes: Transmembrane Potential and Induced pH-Gradient Loading and Leakage of Liposomes

    Science.gov (United States)

    Ceh; Lasic

    1997-01-01

    Many drugs are successfully loaded into preformed liposomes by using various gradients and transmembrane potential. Several experimental breakthroughs, however, have not been paralleled by theoretical understanding of the processes. Recently, we have developed a rigorous treatment of loading of weak acids and bases into liposomes. The model is based on equilibration of chemical potentials of permeable neutral species. Charged molecules are not allowed to permeate the membrane. Although this assumption is quite reasonable and experimental data fit the theoretical predictions rather well, we have extended the model of liposome loading. In the expanded model, terms which allow leakage of protons, buildup of the transmembrane pH gradient, an antiport exchange of various cations with protons, and leakage of other molecules from or into liposomes are added to the basic model.

  12. Effective transcutaneous immunization by antigen-loaded flexible liposome in vivo

    Directory of Open Access Journals (Sweden)

    Li N

    2011-12-01

    follicles. Upon transcutaneous administration, the OVA-encapsulated flexible liposome elicited a strong immune response similar to that of positive control (ie, OVA solution administrated by subcutaneous injection with Al(OH3 as an adjuvant. Co-administration of imiquimod with the OVA-loaded liposome expressed a significant enhancement on the transcutaneous immune responses.Conclusion: Results of this study highlight the nanoscale formulation, flexible liposome, as a promising carrier for the transcutaneous delivery of antigen proteins. Imiquimod was shown to be an effective adjuvant as a transcutaneous immunization enhancer with the potential for transcutaneous vaccine development.Keywords: flexible liposome, transcutaneous vaccine, immunization enhancement, adjuvant

  13. Mathematical modeling based evaluation and simulation of boron removal in bioelectrochemical systems.

    Science.gov (United States)

    Ping, Qingyun; Abu-Reesh, Ibrahim M; He, Zhen

    2016-11-01

    Boron removal is an arising issue in desalination plants due to boron's toxicity. As an emerging treatment concept, bioelectrochemical systems (BES) can achieve potentially cost-effective boron removal by taking advantage of cathodic-produced alkali. Prior studies have demonstrated successful removal of boron in microbial desalination cells (MDCs) and microbial fuel cells (MFCs), both of which are representative BES. Herein, mathematical models were developed to further evaluate boron removal by different BES and understand the key operating factors. The models delivered very good prediction of the boron concentration in the MDC integrated with Donnan Dialysis (DD) system with the lowest relative root-mean-square error (RMSE) of 0.00%; the predication of the MFC performance generated the highest RMSE of 18.55%. The model results of salt concentration, solution pH, and current generation were well fitted with experimental data for RMSE values mostly below 10%. The long term simulation of the MDC-DD system suggests that the accumulation of salt in the catholyte/stripping solution could have a positive impact on the removal of boron due to osmosis-driven convection. The current generation in the MDC may have little influence on the boron removal, while in the MFC the current-driven electromigration can contribute up to 40% of boron removal. Osmosis-induced convection transport of boron could be the major driving force for boron removal to a low level 22.2 in order to avoid boron accumulation in the anolyte effluent.

  14. Lipid conjugated prodrugs for enzyme-triggered liposomal drug delivery to tumors

    DEFF Research Database (Denmark)

    Clausen, Mads Hartvig

    2011-01-01

    For some time we have been developing novel enzyme-triggered prodrugs for drug delivery targeting cancer. The liposomal prodrugs take advantage of the EPR effect to localize to tumors and of the local over-expression of secretory phospholipase A2 in tumors. Compared to conventional liposomal drug...... delivery systems, our prodrug-lipid conjugates have two main advantages: 1) the drugs are covalently linked to the lipids and thus leakage is circumvented and 2) the lipophilic bilayer of the formulated liposomes effectively shields the drugs from the aqueous environment in vivo. Consequently, the strategy...

  15. Novel approaches to treatment of hepatocellular carcinoma and hepatic metastases using thermal ablation and thermosensitive liposomes.

    Science.gov (United States)

    Dewhirst, Mark W; Landon, Chelsea D; Hofmann, Christina L; Stauffer, Paul R

    2013-07-01

    Because of the limitations of surgical resection, thermal ablation is commonly used for the treatment of hepatocellular carcinoma and liver metastases. Current methods of ablation can result in marginal recurrences of larger lesions and in tumors located near large vessels. This review presents a novel approach for extending treatment out to the margins where temperatures do not provide complete treatment with ablation alone, by combining thermal ablation with drug-loaded thermosensitive liposomes. A history of the development of thermosensitive liposomes is presented. Clinical trials have shown that the combination of radiofrequency ablation and doxorubicin-loaded thermosensitive liposomes is a promising treatment.

  16. N-trimethyl chitosan-modified liposomes as carriers for oral delivery of salmon calcitonin.

    Science.gov (United States)

    Huang, Aiwen; Makhlof, Abdallah; Ping, Qineng; Tozuka, Yuichi; Takeuchi, Hirofumi

    2011-11-01

    Therapeutic peptide and protein drugs have high specificity and activity in their functions but present challenges in their administration route, requiring development of new delivery systems to improve their bioavailability. The aim of this work was to investigate the role of N-trimethyl chitosan- (TMC-) coated liposomes in the oral administration of calcitonin. TMC with a degree of quaternization around 78% was synthesized and its mucoadhesive properties were examined in vitro using the mucin-particle method, which confirmed that TMC showed mucoadhesion comparable to that of chitosan. TMC-coated liposomes containing calcitonin were prepared and characterized as having a particle size of 262 nm, zeta potential of 35.8 mV and high entrapment efficiency (89.1%). The in vivo evaluation of mucoadhesion was carried out using confocal laser microscopy to observe the residence time and permeation extent after intragastric administration. The results showed that TMC-coated liposomes prolonged the residence time and increased the penetration effect of the liposomal system compared to non-coated liposomes. The study of pharmacological effects confirmed that TMC-coated liposomes increased the area above the blood calcium concentration-time curves (AAC) from 3.13 ± 20.50 to 448.84 ± 103.56 compared to the calcitonin solution. These results support the feasibility of TMC-coated liposomes as a new oral delivery system for peptide and protein drugs.

  17. Plasmon resonant gold-coated liposomes for spectrally coded content release

    Science.gov (United States)

    Leung, Sarah J.; Troutman, Timothy S.; Romanowski, Marek

    2009-02-01

    We have recently introduced liposome-supported plasmon resonant gold nanoshells (Troutman et al., Adv. Mater. 2008, 20, 2604-2608). These plasmon resonant gold-coated liposomes are degradable into components of a size compatible with renal clearance, potentially enabling their use as multifunctional agents in applications in nanomedicine, including imaging, diagnostics, therapy, and drug delivery. The present research demonstrates that laser illumination at the wavelength matching the plasmon resonance band of a gold-coated liposome leads to the rapid release of encapsulated substances, which can include therapeutic and diagnostic agents. Leakage of encapsulated contents is monitored through the release of self-quenched fluorescein, which provides an increase in fluorescence emission upon release. Moreover, the resonant peak of these gold-coated liposomes is spectrally tunable in the near infrared range by varying the concentration of gold deposited on the surface of liposomes. Varying the plasmon resonant wavelengths of gold-coated liposomes can provide a method for spectrally-coding their light-mediated content release, so that the release event is initiated by the specific wavelength of light used to illuminate the liposomes. The development of spectrally-coded release can find applications in controlled delivery of multiple agents to support complex diagnostic tests and therapeutic interventions.

  18. Coupling of drug containing liposomes to microbubbles improves ultrasound triggered drug delivery in mice.

    Science.gov (United States)

    Cool, Steven K; Geers, Bart; Roels, Stefan; Stremersch, Stephan; Vanderperren, Katrien; Saunders, Jimmy H; De Smedt, Stefaan C; Demeester, Joseph; Sanders, Niek N

    2013-12-28

    Local extravasation and triggered drug delivery by use of ultrasound and microbubbles is a promising strategy to target drugs to their sites of action. In the past we have developed drug loaded microbubbles by coupling drug containing liposomes to the surface of microbubbles. Until now the advantages of this drug loading strategy have only been demonstrated in vitro. Therefore, in this paper, microbubbles with indocyanine green (ICG) containing liposomes at their surface or a mixture of ICG-liposomes and microbubbles was injected intravenously in mice. Immediately after injection the left hind leg was exposed to 1 MHz ultrasound and the ICG deposition was monitored 1, 4 and 7 days post-treatment by in vivo fluorescence imaging. In mice that received the ICG-liposome loaded microbubbles the local ICG deposition was, at each time point, about 2-fold higher than in mice that received ICG-liposomes mixed with microbubbles. We also showed that the perforations in the blood vessels allow the passage of ICG-liposomes up to 5h after microbubble and ultrasound treatment. An increase in tissue temperature to 41°C was observed in all ultrasound treated mice. However, ultrasound tissue heating was excluded to cause the local ICG deposition. We concluded that coupling of drug containing liposomes to microbubbles may increase ultrasound mediated drug delivery in vivo.

  19. Preparation and characterization of cosmeceutical liposomes loaded with avobenzone and arbutin.

    Science.gov (United States)

    Liu, Jun-Jen; Nazzal, Sami; Chang, Tzu-Shan; Tsai, Tsuimin

    2013-01-01

    The objective of this study was to develop and characterize a liposome delivery system coencapsulating two cosmeceutical ingredients, avobenzone (AVO) and arbutin (AR). Two different liposome preparation methods, that is, thin film hydration and reverse-phase evaporation, were evaluated. To obtain the optimal formulation, various ratios of lipid to AVO or AR were tested. The effects of liposome formulation and preparation method on particle size, entrapment efficiency (EE), and skin permeation rate were studied. The mean particle size of the liposome formulations obtained by the thin film hydration method was smaller than that obtained by the reverse-phase evaporation method. The EE of AR and AVO in liposomes prepared by the thin film method, however, was lower than that prepared by the reverse-phase evaporation method. No differences in membrane permeation were observed between the two preparation methods. A large portion of AR permeated through the membrane into the receptor chamber. On the other hand, AVO remained in the donor chamber or accumulated in the membrane. The results of this study revealed that liposomes are a promising delivery system for coencapsulated AR and AVO. Liposomes may aid in retaining the sunscreen (AVO) at the surface of the skin for sun protection meanwhile facilitating the penetration of the whitening agent (AR) into the deeper layers of the skin for whitening effect.

  20. Acoustically-active microbubbles conjugated to liposomes: characterization of a proposed drug delivery vehicle.

    Science.gov (United States)

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

    2007-04-23

    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.

  1. Topical liposome targeting of dyes, melanins, genes, and proteins selectively to hair follicles.

    Science.gov (United States)

    Hoffman, R M

    1998-01-01

    For therapeutic and cosmetic modification of hair, we have developed a hair-follicle-selective macromolecule and small molecule targeting system with topical application of phosphatidylcholine-based liposomes. Liposome-entrapped melanins, proteins, genes, and small-molecules have been selectively targeted to the hair follicle and hair shafts of mice. Liposomal delivery of these molecules is time dependent. Negligible amounts of delivered molecules enter the dermis, epidermis, or bloodstream thereby demonstrating selective follicle delivery. Naked molecules are trapped in the stratum corneum and are unable to enter the follicle. The potential of the hair-follicle liposome delivery system for therapeutic use for hair disease as well as for cosmesis has been demonstrated in 3-dimensional histoculture of hair-growing skin and mouse in vivo models. Topical liposome selective delivery to hair follicles has demonstrated the ability to color hair with melanin, the delivery of the active lac-Z gene to hair matrix cells and delivery of proteins as well. Liposome-targeting of molecules to hair follicles has also been achieved in human scalp in histoculture. Liposomes thus have high potential in selective hair follicle targeting of large and small molecules, including genes, opening the field of gene therapy and other molecular therapy of the hair process to restore hair growth, physiologically restore or alter hair pigment, and to prevent or accelerate hair loss.

  2. Liposomal Indocyanine Green for Enhanced Photothermal Therapy.

    Science.gov (United States)

    Yoon, Hwan-Jun; Lee, Hye-Seong; Lim, Ji-Young; Park, Ji-Ho

    2017-02-22

    In this study, we engineered liposomal indocyanine green (ICG) to maximize its photothermal effects while maintaining the fluorescence intensity. Various liposomal formulations of ICG were prepared by varying the lipid composition and the molar ratio between total lipid and ICG, and their photothermal characteristics were evaluated under near-infrared irradiation. We showed that the ICG dispersity in the liposomal membrane and its physical interaction with phospholipids were the main factors determining the photothermal conversion efficiency. In phototherapeutic studies, the optimized formulation of liposomal ICG showed greater anticancer effects in a mouse tumor model compared with other liposomal formulations and the free form of ICG. Furthermore, we utilized liposomal ICG to visualize the metastatic lymph node around the primary tumor under fluorescence imaging guidance and ablate the lymph node with the enhanced photothermal effect, indicating the potential for selective treatment of metastatic lymph node.

  3. In Vivo Boron Uptake Determination for Boron Neutron Capture Synovectomy

    Energy Technology Data Exchange (ETDEWEB)

    Binello, Emanuela; Shortkroff, Sonya; Yanch, Jacquelyn C.

    1999-06-06

    Boron neutron capture synovectomy (BNCS) has been proposed as a new application of the boron neutron capture reaction for the treatment of rheumatoid arthritis. In BNCS, a boron compound is injected into the joint space, where it is taken up by the synovium. The joint is then irradiated with neutrons of a desired energy range, inducing the boron neutron capture reaction in boron-loaded cells. Boron uptake by the synovium is an important parameter in the assessment of the potential of BNCS and in the determination of whether to proceed to animal irradiations for the testing of therapeutic efficacy. We present results from an investigation of boron uptake in vivo by the synovium.

  4. Development and characteristics of the HANARO ex-core neutron irradiation facility for applications in the boron neutron capture therapy field

    CERN Document Server

    Kim, M S; Jun, B J; Kim, H; Lee, B C; Hwang, Sung-Yul; Jun, Byung-Jin; Kim, Heonil; Kim, Myong-Seop; Lee, Byung-Chul

    2006-01-01

    The HANARO ex-core neutron irradiation facility was developed for various applications in the boron neutron capture therapy (BNCT) field, and its characteristics have been investigated. In order to obtain a sufficient thermal neutron flux with a low level contamination of fast neutrons and gamma-rays, a radiation filtering method is adopted. The radiation filter has been designed by using a silicon single crystal cooled by liquid nitrogen and a bismuth crystal. The installation of the main components of the irradiation facility and the irradiation room are finished. Experimental measurements of the neutron beam characteristics have been performed by using bare and cadmium covered gold foils and wires. The in-phantom neutron flux distribution was measured for a flux mapping inside the phantom. The gamma-ray dose was determined by using TLD-700 thermoluminescence dosimeters. The thermal and fast neutron fluxes and the gamma-ray dose were calculated by using the MCNP code, and they were compared with experimenta...

  5. Design calculations of an epithermal neutron beam and development of a treatment planning system for the renovation of thor for boron neutron capture therapy

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Y-W H.; Teng, Y.H.; Liao, M.Z. [National Tsing Hua Univ., Department of Engineering and System Science, Taiwan (China)

    2000-10-01

    Tsing Hua University was recently granted by National Science Council a five-year project to renovate its Open-Pool reactor (THOR) for boron neutron capture therapy. With this support, the whole graphite blocks in the original thermal column region can be removed for redesigning and constructing a better epithermal neutron beam. THOR is a 1 MW research reactor. The cross section area of the core facing the thermal column is 60 cm x 50 cm. By using 60 cm FLUENTAL plus 10 cm Pb, with cross section area of 70 cm x 60 cm and surrounded by 6 cm thick PbF{sub 2} reflector, the epithermal neutron flux at the filter/moderator exit can reach {approx}8.5 x 10{sup 9} n/cm{sup 2}/s. When the collimator is added, the epithermal neutron beam intensity at the beam exit is reduced to 3 x 10{sup 9} n/cm{sup 2}/sec, but is still six times higher than the previous beam. Facing the clinical trials scheduled 3 and half years from now, a preliminary version of treatment planning system is developed. It includes a pre-processor to read CT scan and post-processors to display dose distributions. (author)

  6. Evaluation of Extrusion Technique for Nanosizing Liposomes

    Directory of Open Access Journals (Sweden)

    Sandy Gim Ming Ong

    2016-12-01

    Full Text Available The aim of the present study was to study the efficiency of different techniques used for nanosizing liposomes. Further, the aim was also to evaluate the effect of process parameters of extrusion techniques used for nanosizing liposomes on the size and size distribution of the resultant liposomes. To compare the efficiency of different nanosizing techniques, the following techniques were used to nanosize the liposomes: extrusion, ultrasonication, freeze-thaw sonication (FTS, sonication and homogenization. The extrusion technique was found to be the most efficient, followed by FTS, ultrasonication, sonication and homogenization. The extruder used in the present study was fabricated using readily available and relatively inexpensive apparatus. Process parameters were varied in extrusion technique to study their effect on the size and size distribution of extruded liposomes. The results obtained indicated that increase in the flow rate of the extrusion process decreased the size of extruded liposomes however the size homogeneity was negatively impacted. Furthermore, the liposome size and distribution was found to decline with decreasing membrane pore size. It was found that by extruding through a filter with a pore size of 0.2 µm and above, the liposomes produced were smaller than the pore size, whereas, when they were extruded through a filter with a pore size of less than 0.2 µm the resultant liposomes were slightly bigger than the nominal pore size. Besides that, increment of extrusion temperature above transition temperature of the pro-liposome had no effect on the size and size distribution of the extruded liposomes. In conclusion, the extrusion technique was reproducible and effective among all the methods evaluated. Furthermore, processing parameters used in extrusion technique would affect the size and size distribution of liposomes. Therefore, the process parameters need to be optimized to obtain a desirable size range and homogeneity

  7. Parenteral emulsions and liposomes to treat drug overdose.

    Science.gov (United States)

    Damitz, Robert; Chauhan, Anuj

    2015-08-01

    Drug overdoses from both pharmaceutical and recreational drugs are a major public health concern. Although some overdoses may be treated with specific antidotes, the most common treatment involves providing supportive care to allow the body to metabolize and excrete the toxicant. In many cases, supportive care is limiting, ineffective, and expensive. There is a clear medical need to improve the effectiveness of detoxification, in particular by developing more specific therapies or antidotes for these overdoses. Intravenous lipid emulsions (ILEs) have been investigated as a potential treatment for overdoses of local anesthetics and other hydrophobic drugs. While ILE therapy has been successful in several cases, its use beyond local anesthetic systemic toxicity is controversial and its mechanism of detoxification remains a subject of debate. ILEs were not originally developed to treat overdose, but clarifying the mechanisms of detoxification observed with ILE may allow us to design more effective future treatments. Liposomes are highly biocompatible and versatile formulations, thus it was a natural step to explore their use for drug overdose therapy as well. Several researchers have designed liposomes using a variety of approaches including surface charge, pH gradients, and inclusion of enzymes in the liposome core to optimize the formulations for detoxification of a specific drug or toxicant. The in vitro results for drug sequestration by liposomes are very promising and animal trials have in some cases shown comparable performance to ILE at reduced lipid dosing. This narrative review summarizes the current status and advances in the use of emulsions and liposomes for detoxification and also suggests several areas in which studies are needed for developing future therapies.

  8. A convenient catalyst system for microwave accelerated cross-coupling of a range of aryl boronic acids with aryl chlorides

    Directory of Open Access Journals (Sweden)

    Milton Edward J

    2007-05-01

    Full Text Available Abstract A convenient microwave accelerated cross-coupling procedure between aryl chlorides with a range of boronic acids has been developed. An explanation for the low reactivity of highly fluorinated boronic acids in Suzuki coupling is provided.

  9. Interactions of liposomes with dental restorative materials.

    Science.gov (United States)

    Nguyen, Sanko; Adamczak, Malgorzata; Hiorth, Marianne; Smistad, Gro; Kopperud, Hilde Molvig

    2015-12-01

    The in vitro adsorption and retention of liposomes onto four common types of dental restorative materials (conventional and silorane-based resin composites as well as conventional and resin-modified glass ionomer cements (GIC)) have been investigated due to their potential use in the oral cavity. Uncoated liposomes (positively and negatively charged) and pectin (low- and high-methoxylated) coated liposomes were prepared and characterized in terms of particle size and zeta potential. The adsorption of liposomes was performed by immersion, quantified by fluorescence detection, and visualized by fluorescence imaging and atomic force microscopy. Positive liposomes demonstrated the highest adsorption on all four types of materials likely due to their attractive surface charge. They also retained well (minimum 40% after 60 min) on both conventional resin composite and GIC even when exposed to simulated salivary flow. Although an intermediate initial level of adsorption was found for the pectin coated liposomes, at least 70% high methoxylated-pectin coated liposomes still remained on the conventional resin composite after 60 min flow exposure. This indicates significant contribution of hydrophobic interactions in the prolonged binding of liposomes to resin composites. Based on these results, the present paper suggests two new possible applications of liposomes in the preservation of dental restorations.

  10. Liposomal drug delivery systems--clinical applications.

    Science.gov (United States)

    Goyal, Parveen; Goyal, Kumud; Vijaya Kumar, Sengodan Gurusamy; Singh, Ajit; Katare, Om Prakash; Mishra, Dina Nath

    2005-03-01

    Liposomes have been widely investigated since 1970 as drug carriers for improving the delivery of therapeutic agents to specific sites in the body. As a result, numerous improvements have been made, thus making this technology potentially useful for the treatment of certain diseases in the clinics. The success of liposomes as drug carriers has been reflected in a number of liposome-based formulations, which are commercially available or are currently undergoing clinical trials. The current pharmaceutical preparations of liposome-based therapeutic systems mainly result from our understanding of lipid-drug interactions and liposome disposition mechanisms. The insight gained from clinical use of liposome drug delivery systems can now be integrated to design liposomes that can be targeted on tissues, cells or intracellular compartments with or without expression of target recognition molecules on liposome membranes. This review is mainly focused on the diseases that have attracted most attention with respect to liposomal drug delivery and have therefore yielded most progress, namely cancer, antibacterial and antifungal disorders. In addition, increased gene transfer efficiencies could be obtained by appropriate selection of the gene transfer vector and mode of delivery.

  11. Liposomal cancer therapy: exploiting tumor characteristics

    DEFF Research Database (Denmark)

    Kaasgaard, Thomas; Andresen, Thomas Lars

    2010-01-01

    of cancer treatments. In the search for more effective cancer treatments, nanoparticle- based drug delivery systems, such as liposomes, that are capable of delivering their drug payload selectively to cancer cells are among the most promising approaches. Areas covered in this review: This review provides...... of new liposomal drug delivery systems that better exploit tumor characteristic features is likely to result in more efficacious cancer treatments....... an overview of current strategies for improving the different stages of liposomal cancer therapy, which involve transporting drug-loaded liposomes through the bloodstream, increasing tumor accumulation, and improving drug release and cancer cell uptake after accumulation at the tumor target site. What...

  12. Coupling of Ligands to the Liposome Surface by Click Chemistry.

    Science.gov (United States)

    Spanedda, Maria Vittoria; De Giorgi, Marcella; Hassane, Fatouma Saïd; Schuber, Francis; Bourel-Bonnet, Line; Frisch, Benoît

    2017-01-01

    Click chemistry represents a new bioconjugation strategy that can be used to conveniently attach various ligands to the surface of preformed liposomes. This efficient and chemoselective reaction involves a Cu(I)-catalyzed azide-alkyne cycloaddition which can be performed under mild experimental conditions in aqueous media. Here we describe the application of a model click reaction to the conjugation, in a single step, of unprotected α-1-thiomannosyl ligands, functionalized with an azide group, to liposomes containing a terminal alkyne-functionalized lipid anchor. Excellent coupling yields have been obtained in the presence of bathophenanthroline disulfonate, a water soluble copper-ion chelator, acting as a catalyst. No vesicle leakage is triggered by this conjugation reaction and the coupled mannose ligands are exposed at the surface of the liposomes. The major limitation of Cu(I)-catalyzed click reactions is that this conjugation is restricted to liposomes made of saturated (phospho)lipids. To circumvent that constraint, an example of alternative copper-free azide-alkyne click reaction has been developed. Molecular tools and results are presented here.

  13. Single cell targeting using plasmon resonant gold-coated liposomes

    Science.gov (United States)

    Leung, Sarah J.; Romanowski, Marek

    2012-03-01

    We have developed an experimental system with the potential for the delivery and localized release of an encapsulated agent with high spatial and temporal resolution. We previously introduced liposome-supported plasmon resonant gold nanoshells; in this composite structure, the liposome allows for the encapsulation of substances, such as therapeutic agents, neurotransmitters, or growth factors, and the plasmon resonant structure facilitates the rapid release of encapsulated contents upon laser light illumination. More recently, we demonstrated that these gold-coated liposomes are capable of releasing their contents in a spectrally-controlled manner, where plasmon resonant nanoparticles only release content upon illumination with a wavelength of light matching their plasmon resonance band. We now show that this release mechanism can be used in a biological setting to deliver a peptide derivative of cholecystokinin to HEK293 cells overexpressing the CCK2 receptor. Using directed laser light, we may enable localized release from gold-coated liposomes to enable accurate perturbation of cellular functions in response to released compounds; this system may have possible applications in signaling pathways and drug discovery.

  14. Liposomal photosensitizers: potential platforms for anticancer photodynamic therapy

    Directory of Open Access Journals (Sweden)

    L.A. Muehlmann

    2011-08-01

    Full Text Available Photodynamic therapy is a well-established and clinically approved treatment for several types of cancer. Antineoplastic photodynamic therapy is based on photosensitizers, i.e., drugs that absorb photons translating light energy into a chemical potential that damages tumor tissues. Despite the encouraging clinical results with the approved photosensitizers available today, the prolonged skin phototoxicity, poor selectivity for diseased tissues, hydrophobic nature, and extended retention in the host organism shown by these drugs have stimulated researchers to develop new formulations for photodynamic therapy. In this context, due to their amphiphilic characteristic (compatibility with both hydrophobic and hydrophilic substances, liposomes have proven to be suitable carriers for photosensitizers, improving the photophysical properties of the photosensitizers. Moreover, as nanostructured drug delivery systems, liposomes improve the efficiency and safety of antineoplastic photodynamic therapy, mainly by the classical phenomenon of extended permeation and retention. Therefore, the association of photosensitizers with liposomes has been extensively studied. In this review, both current knowledge and future perspectives on liposomal carriers for antineoplastic photodynamic therapy are critically discussed.

  15. Liposome encapsulated of temozolomide for the treatment of glioma tumor: preparation, characterization and evaluation.

    Science.gov (United States)

    Gao, Jinhua; Wang, Zhonglan; Liu, Honghai; Wang, Longmei; Huang, Guihua

    2015-06-01

    Temozolomide plays a critical role in curing glioma at present. The purpose of this work was to develop a suitable drug delivery system which could prolong the half-life, improve the brain targeting, and reduce the systemic effect of the drug. Temozolomide-liposomes were formulated by the method of proliposomes. They were found to be relatively uniform in size of 156.70 ± 11.40 nm with a narrow polydispersity index (PI) of 0.29 ± 0.04. The average drug entrapment efficiency and loading capacity were 35.45 ± 1.48% and 2.81 ± 0.20%, respectively. The pH of temozolomide-liposomes was 6.46. In vitro release studies were conducted by a dynamic dialysis. The results showed that temozolomide released slowly from liposomes compared with the solution group. The release behavior of temozolomide-liposomes was in line with First-order kinetics and Weibull equation. The pharmacokinetics study was evaluated by pharmacokinetics parameters. The t(1/2β) and MRT of temozolomide-liposomes were 3.57 times and 1.27 times greater than that of temozolomide solution. The Cmax and AUC values of temozolomide-liposomes were 1.10 times and 1.55 times greater than that of temozolomide solution. The results of pharmacokinetics study showed temozolomide-liposomes prolonged the in vivo circulation time and increased AUC. Furthermore, the biodistribution in mice showed that temozolomide-liposomes preferentially decreased the accumulation of temozolomide in heart and lung and increased the drug concentration in brain after i.v. injection, which implied that temozolomide-liposomes improved the therapeutic effect in the brain and reduced the toxicity in lung and heart.

  16. A simplified method to attach antibodies on liposomes by biotin-streptavidin affinity for rapid and economical screening of targeted liposomes.

    Science.gov (United States)

    Papadia, Konstantina; Markoutsa, Eleni; Antimisiaris, Sophia G

    2014-05-01

    The biotin-Streptavidin (STREP) technique for attachment of monoclonal antibodies (mAbs) (or other ligand types) on liposome surface offers high attachment yield, however it is time consuming and expensive due to the number of steps used and the consumption of large quantities of STREP. Herein, a simplified, fast and economic technique, by incubating pre-mixed biotin-mAb/STREP with biotin-liposomes, at a 3:1:1 biotin-mAb/STREP/biotin-LIP ratio (mol/mol/mol) was evaluated. The physichochemical properties, final mAb attachment yield and targeting potential of liposomes decorated with an anti-transferrin receptor mAb (TfR-mAb), prepared by the simple method (SM) and the conventional method (CM), were compared. The vesicle uptake by hCMEC/D3 cells (known to overexpress TfR) were considered as a measure of liposome targeting capability. Results show that both targeted liposome types (SM and CM) have small size (mean diameters around 150 nm), low poly-dispersity (approx. 0.20) and similar mAb attachment yield (between 64-88%). However, the uptake of the SM-liposomes is slightly lower compared to CM-LIP (24-30% decrease), suggesting that the modulated conformation of mAbs on the liposome surface (triplets attached to one single STREP molecule) results in decreased targeting capability. Nevertheless, the simpler and faster one-step preparation procedure which has very high lipid recovery (> 95%) compared to the CM (50-60%) and 15-30 times lower consumption of STREP, may be a good alternative for initial screening of various mAbs as ligands for targeted liposomal or other nanotechnologies, during pre-clinical development.

  17. Numerical simulation of boron injection in a BWR

    Energy Technology Data Exchange (ETDEWEB)

    Tinoco, Hernan, E-mail: htb@forsmark.vattenfall.s [Forsmarks Kraftgrupp AB, SE-742 03 Osthammar (Sweden); Buchwald, Przemyslaw [Reactor Technology, Royal Institute of Technology, SE-100 44 Stockholm (Sweden); Frid, Wiktor, E-mail: wiktor@reactor.sci.kth.s [Reactor Technology, Royal Institute of Technology, SE-100 44 Stockholm (Sweden)

    2010-02-15

    The present study constitutes a first step to understand the process of boron injection, transport and mixing in a BWR. It consists of transient CFD simulations of boron injection in a model of the downcomer of Forsmark's Unit 3 containing about 6 million elements. The two cases studied are unintentional start of boron injection under normal operation and loss of offsite power with partial ATWS leaving 10% of the core power uncontrolled. The flow conditions of the second case are defined by means of an analysis with RELAP5, assuming boron injection start directly after the first ECCS injection. Recent publications show that meaningful conservative results may be obtained for boron or thermal mixing in PWRs with grids as coarse as that utilized here, provided that higher order discretization schemes are used to minimize numerical diffusion. The obtained results indicate an apparently strong influence of the scenario in the behavior of the injection process. The normal operation simulation shows that virtually all boron solution flows down to the Main Recirculation Pump inlet located directly below the boron inlet nozzle. The loss of offsite power simulation shows initially a spread of the boron solution over the entire sectional area of the lower part of the downcomer filled with colder water. This remaining effect of the ECCS injection lasts until all this water has left the downcomer. Above this region, the boron injection jet develops in a vertical streak, eventually resembling the injection of the normal operation scenario. Due to the initial spread, this boron injection will probably cause larger temporal and spatial concentration variations in the core. In both cases, these variations may cause reactivity transients and fuel damage due to local power escalation. To settle this issue, an analysis using an extended model containing the downcomer, the MRPs and the Lower Plenum will be carried out. Also, the simulation time will be extended to a scale of

  18. Impedimetric toxicity assay in microfluidics using free and liposome-encapsulated anticancer drugs

    DEFF Research Database (Denmark)

    Caviglia, Claudia; Zor, Kinga; Montini, Lucia;

    2015-01-01

    In this work, we have developed a microfluidic cytotoxicity assay for a cell culture and detection platform, which enables both fluid handling and electrochemical/optical detection. The cytotoxic effect of anticancer drugs doxorubicin (DOX), oxaliplatin (OX) as well as OX-loaded liposomes......, developed for targeted drug delivery, was evaluated using real-time impedance monitoring. The time-dependent effect of DOX on HeLa cells was monitored and found to have a delayed onset of cytotoxicity in microfluidics compared with static culture conditions based on data obtained in our previous study......-dependent cytotoxic response of fibrosarcoma cells (HT1080) to free OX and OX-loaded liposomes was observed and attributed to incomplete degradation of the liposomes, which results in lower drug availability. The matrix metalloproteinase (MMP)-dependent release of OX from OX-loaded liposomes was also confirmed using...

  19. Boron removal by electrocoagulation and recovery.

    Science.gov (United States)

    Isa, Mohamed Hasnain; Ezechi, Ezerie Henry; Ahmed, Zubair; Magram, Saleh Faraj; Kutty, Shamsul Rahman Mohamed

    2014-03-15

    This work investigated the removal of boron from wastewater and its recovery by electrocoagulation and hydrothermal mineralization methods respectively. The experimental design was developed using Box-Behnken Model. An initial study was performed based on four preselected variables (pH, current density, concentration and time) using synthetic wastewater. Response surface methodology (RSM) was used to evaluate the effect of process variables and their interaction on boron removal. The optimum conditions were obtained as pH 6.3, current density 17.4 mA/cm(2), and time 89 min. At these applied optimum conditions, 99.7% boron removal from an initial concentration of 10.4 mg/L was achieved. The process was effectively optimized by RSM with a desirability value of 1.0. The results showed that boron removal efficiency enhanced with increase in current density and treatment time. Removal efficiency also increased when pH was increased from 4 to 7 and subsequently decreased at pH 10. Adsorption kinetics study revealed that the reaction followed pseudo second order kinetic model; evidenced by high correlation and goodness of fit. Thermodynamics study showed that mechanism of boron adsorption was chemisorption and the reaction was endothermic in nature. Furthermore, the adsorption process was spontaneous as indicated by negative values of the adsorption free energy. Treatment of real produced water using electrocoagulation resulted in 98% boron removal. The hydrothermal mineralization study showed that borate minerals (Inyoite, Takadaite and Nifontovite) can be recovered as recyclable precipitate from electrocoagulation flocs of produced water.

  20. Separation and Analysis of Boron Isotope in High Plant by Thermal Ionization Mass Spectrometry

    Directory of Open Access Journals (Sweden)

    Qingcai Xu

    2015-01-01

    Full Text Available Knowledge of boron and its isotope in plants is useful to better understand the transposition and translocation of boron within plant, the geochemical behavior in the interface between soil and plant, and the biogeochemical cycle of boron. It is critical to develop a useful method to separate boron from the plant for the geochemical application of boron and its isotope. A method was developed for the extraction of boron in plant sample, whose isotope was determined by thermal ionization mass spectrometry. The results indicated that this method of dry ashing coupled with two-step ion-exchange chromatography is powerful for the separation of boron in plant sample with large amounts of organic matters completely. The ratios of boron isotope composition in those plant tissue samples ranged from -19.45‰ to +28.13‰ (total range: 47.58‰ with a mean value of 2.61±11.76‰ SD. The stem and root isotopic compositions were lower than those in flower and leaf. The molecular mechanism of boron isotope may be responsible for the observed variation of boron isotopic composition and are considered as a useful tool for the better understanding of boron cycling process in the environment and for the signature of living systems.

  1. Cryogenic transmission electron microscopy of recombinant tuberculosis vaccine antigen with anionic liposomes reveals formation of flattened liposomes

    Directory of Open Access Journals (Sweden)

    Fox CB

    2014-03-01

    Full Text Available Christopher B Fox,1 Sean K Mulligan,2 Joyce Sung,2 Quinton M Dowling,1 H W Millie Fung,1 Thomas S Vedvick,1 Rhea N Coler1 1Infectious Disease Research Institute, Seattle, WA, USA; 2NanoImaging Services, La Jolla, CA, USA Abstract: Development of lipid-based adjuvant formulations to enhance the immunogenicity of recombinant vaccine antigens is a focus of modern vaccine research. Characterizing interactions between vaccine antigens and formulation excipients is important for establishing compatibility between the different components and optimizing vaccine stability and potency. Cryogenic transmission electron microscopy (TEM is a highly informative analytical technique that may elucidate various aspects of protein- and lipid-based structures, including morphology, size, shape, and phase structure, while avoiding artifacts associated with staining-based TEM. In this work, cryogenic TEM is employed to characterize a recombinant tuberculosis vaccine antigen, an anionic liposome formulation, and antigen–liposome interactions. By performing three-dimensional tomographic reconstruction analysis, the formation of a population of protein-containing flattened liposomes, not present in the control samples, was detected. It is shown that cryogenic TEM provides unique information regarding antigen–liposome interactions not detectable by light-scattering-based methods. Employing a suite of complementary analytical techniques is important to fully characterize interactions between vaccine components. Keywords: vaccine adjuvant; cryo-TEM; antigen-adjuvant interactions; vaccine physical characterization; vaccine formulation morphology; 3D tomographic reconstruction

  2. Boron contamination in drinking - irrigation water and boron removal methods

    Directory of Open Access Journals (Sweden)

    Meltem Bilici Başkan

    2014-03-01

    Full Text Available Boron presents in IIIA group of periodic table and has high ionization capacity. Therefore it is classified as a metalloid. Average boron concentration in earth's crust is 10 mg/kg. It presents in the environment as a salts of Ca, Na, and Mg. Boron reserves having high concentration and economical extent are found mostly in Turkey and in arid, volcanic and high hydrothermal activity regions of U.S. as compounds of boron attached to oxygen. Boron is an essential micronutrient for plants, although it may be toxic at higher levels. The range in which it is converted from a nutrient to a contaminant is quite narrow. Boron presents in water environment as a boric acid and rarely borate salts. The main boron sources, whose presence is detected in surface waters, are urban wastes and industrial wastes, which can come from a wide range of different activities as well as several chemical products used in agriculture. In Turkey, the most pollutant toxic element in drinking and irrigation water is boron. Therefore boron removal is very important in terms of human health and agricultural products in high quality. Mainly boron removal methods from drinking water and irrigation water are ion exchange, ultrafiltration, reverse osmosis, and adsorption.

  3. Plasma boron and the effects of boron supplementation in males.

    Science.gov (United States)

    Green, N R; Ferrando, A A

    1994-11-01

    Recently, a proliferation of athletic supplements has been marketed touting boron as an ergogenic aid capable of increasing testosterone. The effect of boron supplementation was investigated in male bodybuilders. Ten male bodybuilders (aged 20 to 26) were given a 2.5-mg boron supplement, while nine male bodybuilders (aged 21 to 27) were given a placebo for 7 weeks. Plasma total and free testosterone, plasma boron, lean body mass, and strength measurements were determined on day 1 and day 49 of the study. A microwave digestion procedure followed by inductively coupled argon plasma spectroscopy was used for boron determination. Twelve subjects had boron values at or above the detection limit with median value of 25 ng/ml (16 ng/ml lower quartile and 33 ng/ml upper quartile). Of the ten subjects receiving boron supplements, six had an increase in their plasma boron. Analysis of variance indicated no significant effect of boron supplementation on any of the other dependent variables. Both groups demonstrated significant increases in total testosterone (p bodybuilding can increase total testosterone, lean body mass, and strength in lesser-trained bodybuilders, but boron supplementation affects these variables not at all.

  4. Bright prospects for boron

    NARCIS (Netherlands)

    Wassink, J.

    2012-01-01

    Professor Lis Nanver at Dimes has laid the foundation for a range of new photodetectors by creating a thin coating of boron on a silicon substrate. The sensors are used in ASML’s latest lithography machines and FEI’s most sensitive electron microscopes.

  5. Methods of producing continuous boron carbide fibers

    Energy Technology Data Exchange (ETDEWEB)

    Garnier, John E.; Griffith, George W.

    2015-12-01

    Methods of producing continuous boron carbide fibers. The method comprises reacting a continuous carbon fiber material and a boron oxide gas within a temperature range of from approximately 1400.degree. C. to approximately 2200.degree. C. Continuous boron carbide fibers, continuous fibers comprising boron carbide, and articles including at least a boron carbide coating are also disclosed.

  6. Nanoparticle Stabilized Liposomes for Acne Therapy

    Science.gov (United States)

    Fu, Victoria

    Acne vulgaris is a common skin disease that affects over 40 million people in the United States alone. The main cause of acne vulgaris is Propionibacterium acnes (P. acnes), resides deep in the pores and follicles of the skin in order to feed on oil produced by the sebaceous glands. The liposome is a lipid based nanoparticle with numerous advantages over free drug molecules as an acne treatment alternative. Bare liposomes loaded with lauric acid (LipoLA) were found to show strong antimicrobial activity against P. acnes while generating minimal toxicity. However, the platform is limited by the spontaneous tendency of liposomes to fuse with each other. Attaching nanoparticles to the surface of liposomes can overcome this challenge by providing steric repulsion and reduce surface tension. Thus, carboxyl-functionalized gold nanoparticles (AuC) were attached to the surface of liposomes (AuC-liposomes) loaded with doxycycline, a general tetracycline antibiotic. These particles were found to have a diameter of 120 nm and a zeta potential of 20.0 mV. Both fluorescent and antimicrobial studies demonstrated that based on electrostatic interaction, negatively charged AuC attached to the liposome's positively charged surface and stabilized liposomes in a neutral pH environment (pH = 7.4). Upon entering the skin's acidic environment (pH = 4), AuC detached from the liposome's surface and liposomes could fuse with P. acnes residing in the pores. Furthermore, toxicity studies showed that AuC-liposomes did not induce any significant toxicity, while two of the leading over-the-counter therapies, benzoyl peroxide and salicylic acid, generated substantial skin irritation.

  7. Activatable photodynamic destruction of cancer cells by NIR dye/photosensitizer loaded liposomes.

    Science.gov (United States)

    Yuan, Ahu; Tang, Xiaolei; Qiu, Xuefeng; Jiang, Ke; Wu, Jinhui; Hu, Yiqiao

    2015-02-25

    The phototoxicity of Chlorin e6 (Ce6) for photodynamic therapy (PDT) was found to be effectively suppressed by indocyanine green (ICG), a near infrared (NIR) dye. Upon NIR laser irradiation at 808 nm, ICG in the liposomes containing ICG and Ce6 could be degraded, while the phototoxicity of Ce6 could be recovered. In addition, we demonstrate that this newly developed liposomal component can be successfully used for activatable PDT to destroy cancer cells in vitro.

  8. Raman spectroscopic characterization of the core-rim structure in reaction bonded boron carbide ceramics

    Energy Technology Data Exchange (ETDEWEB)

    Jannotti, Phillip; Subhash, Ghatu, E-mail: subhash@ufl.edu [Department of Mechanical and Aerospace Engineering, University of Florida, Gainesville, Florida 32611 (United States); Zheng, James Q.; Halls, Virginia [Program Executive Office—Soldier Protection and Individual Equipment, US Army, Fort Belvoir, Virginia 22060 (United States); Karandikar, Prashant G.; Salamone, S.; Aghajanian, Michael K. [M-Cubed Technologies, Inc., Newark, Delaware 19711 (United States)

    2015-01-26

    Raman spectroscopy was used to characterize the microstructure of reaction bonded boron carbide ceramics. Compositional and structural gradation in the silicon-doped boron carbide phase (rim), which develops around the parent boron carbide region (core) due to the reaction between silicon and boron carbide, was evaluated using changes in Raman peak position and intensity. Peak shifting and intensity variation from the core to the rim region was attributed to changes in the boron carbide crystal structure based on experimental Raman observations and ab initio calculations reported in literature. The results were consistent with compositional analysis determined by energy dispersive spectroscopy. The Raman analysis revealed the substitution of silicon atoms first into the linear 3-atom chain, and then into icosahedral units of the boron carbide structure. Thus, micro-Raman spectroscopy provided a non-destructive means of identifying the preferential positions of Si atoms in the boron carbide lattice.

  9. Nuclisome: a novel concept for radionuclide therapy using targeting liposomes

    Energy Technology Data Exchange (ETDEWEB)

    Fondell, Amelie; Carlsson, Joergen [Uppsala University, Department of Oncology, Radiology, and Clinical Immunology, Unit of Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala (Sweden); Edwards, Katarina; Ickenstein, Ludger M. [Uppsala University, Department of Physical and Analytical Chemistry, Box 579, Uppsala (Sweden); Sjoeberg, Stefan [Uppsala University, Department of Biochemistry and Organic Chemistry, Box 599, Uppsala (Sweden); Gedda, Lars [Uppsala University, Department of Oncology, Radiology, and Clinical Immunology, Unit of Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala (Sweden); Uppsala University, Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala (Sweden)

    2010-01-15

    For the treatment of cancer, the therapeutic potential of short-range, low-energy Auger-electron emitters, such as {sup 125}I, is getting progressively wider recognition. The potency of Auger-electron emitters is strongly dependent on their location in close vicinity to DNA. We have developed a new two-step targeting strategy to transport {sup 125}I into cancer-cell nuclei using PEG-stabilized tumour-cell targeting liposomes named ''Nuclisome-particles''. In the present study, epidermal growth factor (EGF) was used as a tumour-cell-specific agent to target the EGF-receptor (EGFR) and the liposomes were loaded with {sup 125}I-Comp1, a recently synthesized daunorubicin derivative. As analysed with cryo-TEM, the derivative precipitates inside liposomes at a drug-to-lipid molar ratio of 0.05:1. Receptor-specific uptake in cultured U-343MGaCl2:6 tumour cells of EGFR-targeting liposomes increased with time while non-specific and receptor-blocked uptake remained low. Nuclisome-particles were able to target single U-343MGaCl2:6 cells circulating in human blood during 4 h, with low uptake in white blood cells, as demonstrated in an ex vivo system using a Chandler loop. Autoradiography of targeted cells indicates that the grains from the radiolabelled drug are mainly co-localized with the cell nuclei. The successful targeting of the nucleus is shown to provide high-potency cell killing of cultured U-343MGaCl2:6 cells. At the concentration used, Nuclisome-particles were up to five orders of magnitude more effective in cell killing than EGFR-targeting liposomes loaded with doxorubicin. The results thus provide encouraging evidence that our two-step targeting strategy for tumour cell DNA has the potential to become an effective therapy against metastasizing cancer cells in the bloodstream. (orig.)

  10. Hypoglycemic activity and oral bioavailability of insulin-loaded liposomes containing bile salts in rats: the effect of cholate type, particle size and administered dose.

    Science.gov (United States)

    Niu, Mengmeng; Lu, Yi; Hovgaard, Lars; Guan, Peipei; Tan, Yanan; Lian, Ruyue; Qi, Jianping; Wu, Wei

    2012-06-01

    Oral delivery of protein or polypeptide drugs remains a challenge due to gastric and enzymatic degradation as well as poor permeation across the intestinal epithelia. In this study, liposomes containing bile salts were developed as a new oral insulin delivery system. The primary goal was to investigate the effect of cholate type, particle size and dosage of the liposomes on the hypoglycemic activity and oral bioavailability. Liposomes containing sodium glycocholate (SGC), sodium taurocholate (STC) or sodium deoxycholate (SDC) were prepared by a reversed-phase evaporation method. After oral administration, all liposomes elicited a certain degree of hypoglycemic effect in parallel with an increase in blood insulin level. The highest oral bioavailability of approximately 8.5% and 11.0% could be observed with subcutaneous insulin as reference for SGC-liposomes in non-diabetic and diabetic rats, respectively. Insulin-loaded liposomes showed slower and sustained action over a period of over 20 h with peak time around 8-12h. SGC-liposomes showed higher oral bioavailability than liposomes containing STC or SDC and conventional liposomes. The hypoglycemic effect was size-dependent with the highest at 150 nm or 400 nm and was proportionally correlated to the administered dose. The results supported the hypothesis of insulin absorption as intact liposomes.

  11. Design of cholesterol arabinogalactan anchored liposomes for asialoglycoprotein receptor mediated targeting to hepatocellular carcinoma: In silico modeling, in vitro and in vivo evaluation.

    Science.gov (United States)

    Pathak, Pankaj; Dhawan, Vivek; Magarkar, Aniket; Danne, Reinis; Govindarajan, Srinath; Ghosh, Sandipto; Steiniger, Frank; Chaudhari, Pradip; Gopal, Vijaya; Bunker, Alex; Róg, Tomasz; Fahr, Alfred; Nagarsenker, Mangal

    2016-07-25

    We have developed active targeting liposomes to deliver anticancer agents to ASGPR which will contribute to effective treatment of hepatocellular carcinoma. Active targeting is achieved through polymeric ligands on the liposome surface. The liposomes were prepared using reverse phase evaporation method and doxorubicin hydrocholoride, a model drug, was loaded using the ammonium sulphate gradient method. Liposomes loaded with DOX were found to have a particle size of 200nm with more than 90% entrapment efficiency. Systems were observed to release the drug in a sustained manner in acidic pH in vitro. Liposomes containing targeting ligands possessed greater and selective toxicity to ASGPR positive HepG2 cell lines due to specific ligand receptor interaction. Bio-distribution studies revealed that liposomes were concentrated in the liver even after 3h of administration, thus providing conclusive evidence of targeting potential for formulated nanosystems. Tumor regression studies indicated greater tumor suppression with targeted liposomes thereby establishing superiority of the liposomal system. In this work, we used a novel methodology to guide the determination of the optimal composition of the targeting liposomes: molecular dynamics (MD) simulation that aided our understanding of the behaviour of the ligand within the bilayer. This can be seen as a demonstration of the utility of this methodology as a rational design tool for active targeting liposome formulation.

  12. Oxidation of Silicon and Boron in Boron Containing Molten Iron

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    A new process of directly smelting boron steel from boron-containing pig iron has been established. The starting material boron-containing pig iron was obtained from ludwigite ore, which is very abundant in the eastern area of Liaoning Province of China. The experiment was performed in a medium-frequency induction furnace, and Fe2O3 powder was used as the oxidizing agent. The effects of temperature, addition of Fe2O3, basicity, stirring, and composition of melt on the oxidation of silicon and boron were investigated respectively. The results showed that silicon and boron were oxidized simultaneously and their oxidation ratio exceeded 90% at 1 400 ℃. The favorable oxidation temperature of silicon was about 1 300-1 350 C. High oxygen potential of slag and strong stirring enhanced the oxidation of silicon and boron.

  13. Methods for using redox liposome biosensors

    Science.gov (United States)

    Cheng, Quan; Stevens, Raymond C.

    2002-01-01

    The present invention provides methods and compositions for detecting the presence of biologically-important analytes by using redox liposome biosensors. In particular, the present invention provides liposome/sol-gel electrodes suitable for the detection of a wide variety of organic molecules, including but not limited to bacterial toxins.

  14. Liposome-Encapsulated Hemoglobin for Emergency Resuscitation.

    Science.gov (United States)

    1984-10-01

    have infused liposome -encapsulated amphotericin B to treat patients with systemic fungal infections. Their formulation includes 30% dimyristoyl...procedure, including exploring new industrial-scale methodologies for liposome manufacture. In addition we have focused on basic problems of biophysics...circulation persistance of this new formulation , as produced by the Microfluidizer, is obviously necessary. The influence of negatively-charged lipids on

  15. The protein corona of circulating PEGylated liposomes.

    Science.gov (United States)

    Palchetti, Sara; Colapicchioni, Valentina; Digiacomo, Luca; Caracciolo, Giulio; Pozzi, Daniela; Capriotti, Anna Laura; La Barbera, Giorgia; Laganà, Aldo

    2016-02-01

    Following systemic administration, liposomes are covered by a 'corona' of proteins, and preserving the surface functionality is challenging. Coating the liposome surface with polyethylene glycol (PEG) is the most widely used anti-opsonization strategy, but it cannot fully preclude protein adsorption. To date, protein binding has been studied following in vitro incubation to predict the fate of liposomes in vivo, while dynamic incubation mimicking in vivo conditions remains largely unexplored. The main aim of this investigation was to determine whether shear stress, produced by physiologically relevant dynamic flow, could influence the liposome-protein corona. The corona of circulating PEGylated liposome was thoroughly compared with that formed by incubation in vitro. Systematic comparison in terms of size, surface charge and quantitative composition was made by dynamic light scattering, microelectrophoresis and nano-liquid chromatography tandem mass spectrometry (nanoLC-MS/MS). Size of coronas formed under static vs. dynamic incubation did not appreciably differ from each other. On the other side, the corona of circulating liposomes was more negatively charged than its static counterpart. Of note, the variety of protein species in the corona formed in a dynamic flow was significantly wider. Collectively, these results demonstrated that the corona of circulating PEGylated liposomes can be considerably different from that formed in a static fluid. This seems to be a key factor to predict the biological activity of a liposomal formulation in a physiological environment.

  16. Liposomal nanocapsules in food science and agriculture.

    Science.gov (United States)

    Taylor, T Matthew; Davidson, P Michael; Bruce, Barry D; Weiss, Jochen

    2005-01-01

    Liposomes, spherical bilayer vesicles from dispersion of polar lipids in aqueous solvents, have been widely studied for their ability to act as drug delivery vehicles by shielding reactive or sensitive compounds prior to release. Liposome entrapment has been shown to stabilize encapsulated, bioactive materials against a range of environmental and chemical changes, including enzymatic and chemical modification, as well as buffering against extreme pH, temperature, and ionic strength changes. Liposomes have been especially useful to researchers in studies of various physiological processes as models of biological membranes in both eukaryotes and prokaryotes. Industrial applications include encapsulation of pharmaceuticals and therapeutics, cosmetics, anti-cancer and gene therapy drugs. In the food industry, liposomes have been used to deliver food flavors and nutrients and more recently have been investigated for their ability to incorporate food antimicrobials that could aid in the protection of food products against growth of spoilage and pathogenic microorganisms. In this review we briefly introduce key physicochemical properties of liposomes and review competing methods for liposome production. A survey of non-agricultural and food applications of liposomes are given. Finally, a detailed up-to-date summary of the emerging usage of liposomes in the food industry as delivery vehicles of nutrients, nutraceuticals, food additives, and food antimicrobials is provided.

  17. Transfer mechanism of temoporfin between liposomal membranes.

    Science.gov (United States)

    Hefesha, Hossam; Loew, Stephan; Liu, Xiangli; May, Sylvio; Fahr, Alfred

    2011-03-30

    The transfer kinetics of temoporfin, a classic photosensitizer, was analyzed by investigating the influence of total lipid content, temperature, as well as charge, acyl chain length, and saturation of the lipids in donor vesicles using a mini ion exchange column technique. The obtained results are consistent with an apparent first order kinetics in which the transfer proceeds through both liposome collisions and through the aqueous phase. We present a corresponding theoretical model that accounts for the detailed distribution of drug molecules in donor and acceptor liposomes and predicts the transfer rates as a function of drug concentration and number of donor and acceptor liposomes. The experimentally observed transfer rates depended strongly on the temperature and comply with the Arrhenius equation. Thermodynamic calculations indicate the transfer process to be entropically controlled. In terms of the charge of donor liposomes, positively charged liposomes showed transfer rates faster than negatively charged liposomes whereas the maximum amount transferred was almost the same. A more rigid structure of the donor liposomes increases the transfer rate of temoporfin, which is caused by expelling the drug from the membrane interior, as proposed in former work. In summary, our combined theoretical/experimental approach offers a systematic way to study the mechanism of drug release from liposome-based delivery systems.

  18. Anomalous freezing behavior of nanoscale liposomes

    DEFF Research Database (Denmark)

    Spangler, E. J.; Kumar, P. B. S.; Laradji, M.

    2012-01-01

    The effect of the finite size of one-component liposomes on their phase behavior is investigated via simulations of an implicit-solvent model of self-assembled lipid bilayers. We found that the high curvature of nanoscale liposomes has a significant effect on their freezing behavior. While...

  19. Carbon nanotubes-liposomes conjugate as a platform for drug delivery into cells.

    Science.gov (United States)

    Karchemski, Faina; Zucker, Daniel; Barenholz, Yechezkel; Regev, Oren

    2012-06-10

    Carbon nanotubes (CNT) are widely explored as carriers for drug delivery due to their facile transport through cellular membranes. However, the amount of loaded drug on a CNT is rather small. Liposomes, on the other hand, are employed as a carrier of a large amount of drug. The aim of this research is to develop a new drug delivery system, in which drug-loaded liposomes are covalently attached to CNT to form a CNT-liposomes conjugate (CLC). The advantage of this novel approach is the large amount of drug that can be delivered into cells by the CLC system, thus preventing potential adverse systemic effects of CNT when administered at high doses. This system is expected to provide versatile and controlled means for enhanced delivery of one or more agents stably associated with the liposomes.

  20. Design and characterization of anionic PEGylated liposomal formulation loaded with paclitax for ovarian cancer

    Directory of Open Access Journals (Sweden)

    K Makwana

    2012-01-01

    Full Text Available Despite its strong antitumor activity, paclitaxel (Taxol® has limited clinical applications due to its low aqueous solubility and hypersensitivity caused by cremophor EL and ethanol which is the vehicle used in the current commercial product. In an attempt to develop a pharmaceutically acceptable formulation that could replace Taxol® , we have prepared PEGylated liposomes containing paclitaxel to improve its solubility and physicochemical stability. Its percent drug entrapment (PDE, mean particle size, zeta potential and in vitro release profile were determined. The optimized PEGylated liposomes provided high percent entrapment efficiency (64.29% and mean particle size of 228.6 nm. The electroflocculation method showed 5 mol% of DSPE-mPEG2000 was required to obtain maximum stability for PEGylated liposome. In vitro release data showed its long circulating characteristic. Paclitaxel loaded PEGylated liposomes can be considered a promising long circulating paclitaxel delivery with absence of side effects related to Taxol® .

  1. Light-triggered liposomal cargo delivery platform incorporating photosensitizers and gold nanoparticles for enhanced singlet oxygen generation and increased cytotoxicity

    Science.gov (United States)

    Kautzka, Zofia; Clement, Sandhya; Goldys, Ewa M; Deng, Wei

    2017-01-01

    We developed light-triggered liposomes incorporating 3–5 nm hydrophobic gold nanoparticles and Rose Bengal (RB), a well-known photosensitizer used for photodynamic therapy. Singlet oxygen generated by these liposomes with 532 nm light illumination was characterized for varying the molar ratio of lipids and gold nanoparticles while keeping the amount of RB constant. Gold nanoparticles were found to enhance the singlet oxygen generation rate, with a maximum enhancement factor of 1.75 obtained for the molar ratio of hydrogenated soy l-α-phosphatidylcholine:1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-(hexanoylamine):gold of 57:5:17 compared with liposomes loaded with RB alone. The experimental results could be explained by the local electric field enhancement caused by gold nanoparticles. We further assessed cellular cytotoxicity of gold-loaded liposomes by encapsulating an antitumor drug, doxorubicin (Dox); such Dox-loaded liposomes were applied to human colorectal cancer cells (HCT116) and exposed to light. Gold-loaded liposomes containing RB and Dox where Dox release was triggered by light were found to exhibit higher cytotoxicity compared with the liposomes loaded with RB and Dox alone. Our results indicate that gold-loaded liposomes incorporating photosensitizers may serve as improved agents in photodynamic therapy and chemotherapy. PMID:28203076

  2. Advances in boron-10 isotope separation by chemical exchange distillation

    Energy Technology Data Exchange (ETDEWEB)

    Song Shuang, E-mail: chengruoyu2@sina.co [School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072 (China); Mu Yujun; Li Xiaofeng; Bai Peng [School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072 (China)

    2010-01-15

    Advances in boron-10 isotope separation by chemical exchange distillation are reviewed in this article. With a brief introduction of the principle of the separation, the progress on the research of this method and the problems relating to the separation coefficient are discussed. Several new donors, including nitromethane, acetone, methyl isobutyl ketone (MIBK) and diisobutyl ketone (DIBK), which have large separation factors are introduced. The complexes of these new donors and boron trifluoride (BF{sub 3}) are more stable than those of using the donors examined before. Among these new donors nitromethane could be a promising substitute for donors in present use to develop new technology of separating boron-10.

  3. Iron-Catalyzed Boron Removal from Molten Silicon in Ammonia

    Science.gov (United States)

    Chen, Zhiyuan; Morita, Kazuki

    2016-12-01

    A high-temperature process of refining metallurgical-grade silicon to solar-grade silicon was developed. In this gas purging treatment, boron impurity in silicon reacts with ammonia and the products are removed as volatiles at high temperature. 1 mass pct metallic iron was added to molten silicon as a catalyst, improving the boron removal ratio from 14 to 80 pct at 1723 K (1450 °C). At 1823 K (1550 °C), this reaction could reduce boron concentration from more than 120 ppmw to activation energy of 329 ± 129 kJ mol-1 was calculated from experimental data.

  4. Click Reactions and Boronic Acids: Applications, Issues, and Potential Solutions

    Directory of Open Access Journals (Sweden)

    Chaofeng Dai

    2010-08-01

    Full Text Available Boronic acids have been widely used in a wide range of organic reactions, in the preparation of sensors for carbohydrates, and as potential pharmaceutical agents. With the growing importance of click reactions, inevitably they are also applied to the synthesis of compounds containing the boronic acid moiety. However, such applications have unique problems. Chief among them is the issue of copper-mediated boronic acid degradation in copper-assisted [2,3]-cycloadditions involving an alkyne and an azido compound as the starting materials. This review summarizes recent developments, analyzes potential issues, and discusses known as well as possible solutions.

  5. Protodeboronation of ortho- and para-phenol boronic acids and application to ortho and meta functionalization of phenols using boronic acids as blocking and directing groups.

    Science.gov (United States)

    Lee, Chun-Young; Ahn, Su-Jin; Cheon, Cheol-Hong

    2013-12-06

    The first metal-free thermal protodeboronation of ortho- and para-phenol boronic acids in DMSO was developed. The protodeboronation was successfully applied to the synthesis of ortho- and meta-functionalized phenols using the boronic acid moiety as a blocking group and a directing group, respectively. Mechanistic studies suggested that this protodeboronation proceeds through the coordination of water to the boron atom followed by σ-bond metathesis.

  6. Boron-Based Hydrogen Storage: Ternary Borides and Beyond

    Energy Technology Data Exchange (ETDEWEB)

    Vajo, John J. [HRL Laboratories, LLC, Malibu, CA (United States)

    2016-04-28

    DOE continues to seek reversible solid-state hydrogen materials with hydrogen densities of ≥11 wt% and ≥80 g/L that can deliver hydrogen and be recharged at moderate temperatures (≤100 °C) and pressures (≤100 bar) enabling incorporation into hydrogen storage systems suitable for transportation applications. Boron-based hydrogen storage materials have the potential to meet the density requirements given boron’s low atomic weight, high chemical valance, and versatile chemistry. However, the rates of hydrogen exchange in boron-based compounds are thus far much too slow for practical applications. Although contributing to the high hydrogen densities, the high valance of boron also leads to slow rates of hydrogen exchange due to extensive boron-boron atom rearrangements during hydrogen cycling. This rearrangement often leads to multiple solid phases occurring over hydrogen release and recharge cycles. These phases must nucleate and react with each other across solid-solid phase boundaries leading to energy barriers that slow the rates of hydrogen exchange. This project sought to overcome the slow rates of hydrogen exchange in boron-based hydrogen storage materials by minimizing the number of solid phases and the boron atom rearrangement over a hydrogen release and recharge cycle. Two novel approaches were explored: 1) developing matched pairs of ternary borides and mixed-metal borohydrides that could exchange hydrogen with only one hydrogenated phase (the mixed-metal borohydride) and only one dehydrogenated phase (the ternary boride); and 2) developing boranes that could release hydrogen by being lithiated using lithium hydride with no boron-boron atom rearrangement.

  7. Glutamine-Loaded Liposomes: Preliminary Investigation, Characterization, and Evaluation of Neutrophil Viability.

    Science.gov (United States)

    Costa, Larissa Chaves; Souza, Bárbara Nayane Rosário Fernandes; Almeida, Fábio Fidélis; Lagranha, Cláudia Jacques; Cadena, Pabyton Gonçalves; Santos-Magalhães, Nereide Stela; Lira-Nogueira, Mariane Cajubá de Britto

    2016-04-01

    Glutamine has received attention due to its ability to ameliorate the immune system response. Once conventional liposomes are readily recognized and captured by immune system cells, the encapsulation of glutamine into those nanosystems could be an alternative to reduce glutamine dosage and target then to neutrophils. Our goals were to nanoencapsulate glutamine into conventional liposomes (Gln-L), develop an analytical high-performance liquid chromatography (HPLC) method for its quantification, and evaluate the viability of neutrophils treated with Gln-L. Liposomes were prepared using the thin-film hydration technique followed by sonication and characterized according to pH, mean size, zeta potential, and drug encapsulation efficiency (EE%). We also aimed to study the effect of liposomal constituent concentrations on liposomal characteristics. The viability of neutrophils was assessed using flow cytometry after intraperitoneal administration of free glutamine (Gln), Gln-L, unloaded-liposome (UL), and saline solution as control (C) in healthy Wistar rats. The selected liposomal formulation had a mean vesicle size of 114.65 ± 1.82 nm with a polydispersity index of 0.30 ± 0.00, a positive surface charge of 36.30 ± 1.38 mV, and an EE% of 39.49 ± 0.74%. The developed chromatographic method was efficient for the quantification of encapsulated glutamine, with a retention time at 3.8 min. A greater viability was observed in the group treated with glutamine encapsulated compared to the control group (17%), although neutrophils remain viable in all groups. Thus, glutamine encapsulated into liposomes was able to increase the number of viable neutrophils at low doses, thereby representing a promising strategy for the treatment of immunodeficiency conditions.

  8. Structures, stability, mechanical and electronic properties of α-boron and α*-boron

    OpenAIRE

    Chaoyu He; J. X. Zhong

    2013-01-01

    The structures, stability, mechanical and electronic properties of α-boron and a promising metastable boron phase (α*-boron) have been studied by first-principles calculations. α-boron and α*-boron consist of equivalent icosahedra B12 clusters in different connecting configurations of “3S-6D-3S” and “2S-6D-4S”, respectively. The total energy calculations show that α*-boron is less stable than α-boron but more favorable than the well-known β-boron and γ-boron at zero pressure. Both α-boron and...

  9. A novel covalent coupling method for coating of capillaries with liposomes in capillary electrophoresis.

    Science.gov (United States)

    Mei, Jie; Xu, Jian-Rong; Xiao, Yu-Xiu; Liao, Xiao-Yan; Qiu, Guo-Fu; Feng, Yu-Qi

    2008-09-01

    A novel covalent coupling method for coating of capillaries with liposomes has been developed, which includes three steps: (i) epoxy-diol coating, (ii) activation with 2,2,2-trifluoroethanesulfonyl chloride, and (iii) liposome coupling. The coating conditions, such as the reaction time and temperature of liposome coupling, the content of dimyristoylphosphatidylethanolamine in liposomes, were optimized. Vesicles were visualized on the inner silica wall as confirmed by atomic force microscopy. The effectiveness of the coating was demonstrated by investigating the effect of pH of BGE on EOF and separating neutral compounds. The intra- and inter-capillary variations in EOF are 4.02% RSD (n=30) and 6.72% RSD (n=4) respectively, and the coated capillaries can be used to perform analysis at least for one month without any performance deterioration when stored at 4 degrees C. A set of drugs with diverse structures was applied into the developed liposome-coated CE. The normalized capacity factor (K) was introduced to quantitatively evaluate drug-membrane interactions. The relationship between log K and the fraction dose absorbed in humans (Fa%) shows that the liposome-coated CE can be utilized for in vitro prediction of Fa% of drugs that follow the transcellular passive transport route.

  10. Anti-neuropilin 1 antibody Fab' fragment conjugated liposomal docetaxel for active targeting of tumours.

    Science.gov (United States)

    Manjappa, Arehalli S; Goel, Peeyush N; Gude, Rajiv P; Ramachandra Murthy, Rayasa S

    2014-09-01

    Neuropilin-1, a transmembrane receptor entailed in wide range of human tumour cell lines and diverse neoplasms, mediates the effects of VEGF and Semaphorins during the processes of cellular proliferation, survival and migration. In view of this, we had developed and evaluated in vitro and in vivo efficacy of anti-neuropilin-1 immunoliposomes against neuropilin-1 receptor expressing tumours. The PEGylated liposomes loaded with docetaxel were prepared using thin film hydration method. Functionalised PEGylated liposomes were prepared using post-insertion technique. Anti-neuropilin-1 immunoliposomes were prepared by covalently conjugating Fab' fragments of neuropilin-1 antibody to functionalised PEGylated liposomes via thioether linkage. In vivo evaluation of Taxotere and liposomal formulations was performed using intradermal tumour model to demonstrate anti-angiogenic and tumour regression ability. The modified Fab' fragments and immunoliposomes were found to be immunoreactive against A549 cells. Further, docetaxel loaded PEGylated liposomes and PEGylated immunoliposomes demonstrated higher in vitro cytotoxicity than Taxotere formulation at the same drug concentration and exposure time. The live imaging showed distinctive cellular uptake of functional immunoliposomes. Further, significant decrease in micro-blood vessel density and tumour volumes was observed using bio-engineered liposomes. The results clearly highlight the need to seek neuropilin-1 as one of the prime targets in developing an anti-angiogenic therapy.

  11. Two-dimensional finite elements model for boron management in agroforestry sites.

    Science.gov (United States)

    Tayfur, Gokmen; Tanji, Kenneth K; Baba, Alper

    2010-01-01

    Agroforesty systems, which are recommended as a management option to lower the shallow groundwater level and to reuse saline subsurface drainage waters from the tile-drained croplands in the drainage-impacted areas of Jan Joaquin Valley of California, have resulted in excessive boron buildup in the soil root zone. To assess the efficacy of the long-term impacts of soil boron buildup in agroforesty systems, a mathematical model was developed to simulate non-conservative boron transport. The developed dynamic two-dimensional finite element model simulates water flow and boron transport in saturated-unsaturated soil system, including boron sorption and boron uptake by root-water extraction processes. The simulation of two different observed field data sets by the developed model is satisfactory, with mean absolute error of 1.5 mg/L and relative error of 6.5%. Application of the model to three different soils shows that boron adsorption is higher in silt loam soil than that in sandy loam and clay loam soils. This result agrees with the laboratory experimental observations. The results of the sensitivity analysis indicate that boron uptake by root-water extraction process influences the boron concentration distribution along the root zone. Also, absorption coefficient and maximum adsorptive capacity of a soil for boron are found to be sensitive parameters.

  12. COMPARATIVE STUDY OF CARDIOPROTECTIVE EFFECT OF VARIOUS DIAMETER AND COMPOSITION LIPOSOMES DURING REPERFUSION OF THE ISOLATED RAT HEARTS AFTER NORMOTHERMIC ISCHEMIA

    Directory of Open Access Journals (Sweden)

    Ya. G. Toropova

    2013-01-01

    Full Text Available The wide application of cardiac surgery using the aorto-pulmonary bypass technique needs the development of new drugs, capable to minimize the heart damaging during ischemia and reperfusion. But the direct delivery of drugs into the damaged tissues and cells is a big problem. The liposomes as unique transport system can be used to solve this problem.The aim of the study was to evaluate the influence of "empty" liposomes of various diameter and the liposomes of different composition on the myocardium contractile function which has underwent the ischemia and the subsequent reperfusion. The obtained results allowed us to make the conclusion that liposomes of 50 nanometers in diameter are most effective to cardiac protection versus liposomes of 100 nanometers.Inclusion the emoxipine into the composition of liposomes provide the best results on contractile function of an ischemic myocardium.

  13. Fivefold twinned boron carbide nanowires.

    Science.gov (United States)

    Fu, Xin; Jiang, Jun; Liu, Chao; Yuan, Jun

    2009-09-01

    Chemical composition and crystal structure of fivefold twinned boron carbide nanowires have been determined by electron energy-loss spectroscopy and electron diffraction. The fivefold cyclic twinning relationship is confirmed by systematic axial rotation electron diffraction. Detailed chemical analysis reveals a carbon-rich boron carbide phase. Such boron carbide nanowires are potentially interesting because of their intrinsic hardness and high temperature thermoelectric property. Together with other boron-rich compounds, they may form a set of multiply twinned nanowire systems where the misfit strain could be continuously tuned to influence their mechanical properties.

  14. Anti-inflammatory activity of liposomes of Asparagus racemosus root extracts prepared by various methods

    Science.gov (United States)

    Plangsombat, Nathsiree; Rungsardthong, Kanin; Kongkaneramit, Lalana; Waranuch, Neti; Sarisuta, Narong

    2016-01-01

    Asparagus racemosus root extracts (AR) have been reported to possess a variety of pharmacological properties. The aim of the present study was to develop liposomes of AR and to assess their physicochemical characteristics and anti-inflammatory activity in the monocytic leukemia cell line THP-1. Liposomes containing various ratios of AR to lipid and a phosphatidylcholine to cholesterol molar ratio of 7:3 were prepared by thin-film hydration (TF), reverse-phase evaporation (REV) and polyol dilution (PD). The results showed that AR liposomes prepared by TF had a multilamellar structure and a large size, whereas those prepared by REV and PD were oligolamellar in structure, and of a smaller size. The particle sizes and zeta potentials of the liposomes ranged from 196.5 to 456.6 nm and from −4.34 to −18.94 mV, respectively. The AR to lipid ratio was shown to have no significant influence on particle size, while the zeta potential generally increased with increasing AR to lipid ratio. The highest entrapment efficiency values were detected in liposomes with an AR to lipid ratio of 1:5, and for liposomes prepared by TF, REV and PD methods, the entrapment efficiencies were 55.71±2.04, 56.21±3.59 and 67.68±1.37%, respectively. AR was found to exert no toxicity on THP-1 cells. The maximum anti-inflammatory activities of AR and AR liposomes, evaluated in terms of the percentage inhibition of tumor necrosis factor-α in THP-1 cells, were ~52% at a concentration of 1 µg/ml. It can be concluded from the present study that AR liposomes have the potential to be used a formulation for topical and/or transdermal drug delivery to provide anti-inflammatory activity. PMID:27698785

  15. Use of autoantigen-loaded phosphatidylserine-liposomes to arrest autoimmunity in type 1 diabetes.

    Directory of Open Access Journals (Sweden)

    Irma Pujol-Autonell

    Full Text Available The development of new therapies to induce self-tolerance has been an important medical health challenge in type 1 diabetes. An ideal immunotherapy should inhibit the autoimmune attack, avoid systemic side effects and allow β-cell regeneration. Based on the immunomodulatory effects of apoptosis, we hypothesized that apoptotic mimicry can help to restore tolerance lost in autoimmune diabetes.To generate a synthetic antigen-specific immunotherapy based on apoptosis features to specifically reestablish tolerance to β-cells in type 1 diabetes.A central event on the surface of apoptotic cells is the exposure of phosphatidylserine, which provides the main signal for efferocytosis. Therefore, phosphatidylserine-liposomes loaded with insulin peptides were generated to simulate apoptotic cells recognition by antigen presenting cells. The effect of antigen-specific phosphatidylserine-liposomes in the reestablishment of peripheral tolerance was assessed in NOD mice, the spontaneous model of autoimmune diabetes. MHC class II-peptide tetramers were used to analyze the T cell specific response after treatment with phosphatidylserine-liposomes loaded with peptides.We have shown that phosphatidylserine-liposomes loaded with insulin peptides induce tolerogenic dendritic cells and impair autoreactive T cell proliferation. When administered to NOD mice, liposome signal was detected in the pancreas and draining lymph nodes. This immunotherapy arrests the autoimmune aggression, reduces the severity of insulitis and prevents type 1 diabetes by apoptotic mimicry. MHC class II tetramer analysis showed that peptide-loaded phosphatidylserine-liposomes expand antigen-specific CD4+ T cells in vivo. The administration of phosphatidylserine-free liposomes emphasizes the importance of phosphatidylserine in the modulation of antigen-specific CD4+ T cell expansion.We conclude that this innovative immunotherapy based on the use of liposomes constitutes a promising strategy for

  16. The Effect of Liposome Encapsulated Daunorubicin on Rabbit Eyes after Extracapsular Lens Extraction

    Institute of Scientific and Technical Information of China (English)

    Mingxing Wu; Huaming Li; Shaozhen Li; Junwen Zeng

    2000-01-01

    Purpose: To investigate the effect of liposome encapsulated daunorubicin (DNR) on rabbit eyes when it was used in prevention of posterior capsule opacification (PCO).Methods: The liposome encapsulated DNR was prepared by modified freeze-thawing method. Each eye was injected with 0. 1 ml liposomes (0. 2 mg/ml and 20 μg/mlDNR) into the capsular bag during the extracapsular lens extraction (ECLE) in 10 rabbit eyes respectively. The phosphate buffer solution (PBS) was injected as control. Besides biomicroscope observation and histology examination of all eyes, the concentration of DNR in aqueous humor was also determined by high performance liquid chromatography (HPLC).Results: The morphology of liposome encapsulated DNR were similar to the blank liposome with round or ellipse shape. The encapsulated effecieney of liposome encapsulated DNR was 45.1%. The inflammatory response was much more severe both in 0. 2 mg/ml and 20 μg/ml DNR group than the control after liposome injection. All eyes in DNR group were showed severe corneal edema and opacity and lasted for 4 to 8weeks. Histopathological study revealed that lens epithelial proliferation occured by 4weeks and Soemmering' s ring developed by 8 weeks in control; However, in DNR group eye only a few LECs remained in the bag and there were obvious corneal edema and eosinophiles infiltration. Corneal endothelial cells were severely lost.Conclusion: The results suggest that liposome encapsulated DNR could inhibit metaplasia and proliferation of remnant lens epithelial cells after ECLE in rabbit eyes,but the severe toxicity must be avoided by further study.

  17. Terbinafine hydrochloride loaded liposome film formulation for treatment of onychomycosis: in vitro and in vivo evaluation.

    Science.gov (United States)

    Tanrıverdi, Sakine Tuncay; Hilmioğlu Polat, Süleyha; Yeşim Metin, Dilek; Kandiloğlu, Gülşen; Özer, Özgen

    2016-01-01

    Onychomycosis is a fungal infection of nail unit that is caused by dermatophytes. Oral Terbinafine hydrochloride (TBF-HCl) is being used for the treatment of onychomycosis since 24 years. The side effects caused by the systemic application and limitations of topical administration of this drug regarding the diffusion through nail lead to the development of a new formulation based on, TBF-HCl-loaded liposome. The newly obtained film formulations were prepared and characterized via several parameters, such as physical appearance, drug content, thickness, bioadhesive properties and tensile strength. In vitro and ex vivo permeation studies were performed to select an optimum film formulation for antifungal activity to show the efficiency of formulations regarding the treatment of onychomycosis. The in vitro release percentages of drug were found 71.6 ± 3.28, 54.4 ± 4.26, 56.1 ± 7.48 and 46.0 ± 2.43 for liposome loaded pullulan films (LI-P, LII-P) and liposome loaded Eudragit films (LI-E, LII-E), respectively. The accumulated drug in the nail plates were found 31.16 ± 4.22, 24.81 ± 5.35, 8.17 ± 1.81 and 8.92 ± 3.37 for LI-P, LII-P, LI-E and LII-E, respectively, which within therapeutic range for all film formulations. The accumulated drug in the nail plate was found within therapeutic range for all film formulations. The efficacy of the selected TBF-HCl-loaded liposome film formulation was compared with TBF-HCl-loaded liposome, ethosome, liposome poloxamer gel and ethosome chitosan gel formulations. It was found that TBF-HCl-loaded liposome film formulation had better antifungal activity on fungal nails which make this liposome film formulation promising for ungual therapy of fungal nail infection.

  18. Transport and regulation mechanism of the colloidal gold liposomes in the brain microvascular endothelial cells

    Institute of Scientific and Technical Information of China (English)

    WANG Lipeng; CHANG Yanzhong

    2015-01-01

    nano drug carriers across the BBB. This work has impor-tant theoretical and practical significance for the development and application of liposomes in the future. Results:For untreated cerebral microvascular endothelial cells, the cells incubated with colloidal gold liposomes can uptake of liposome colloidal gold, and with the extension of time, there are gold colloids in the plasma membrane, endo-plasmic reticulum, Golgi apparatus and lysosomes in order, and finally colloidal gold liposome exports out of the cell. For cerebral microvascular endothelial cells treated by sodium azide, compared with untreated cells, the cells incubated with colloidal gold liposomes, cannot be observed liposome colloidal gold in them. For cerebral microvas-cular endothelial cells treated by reserpine, the cells incubated with colloidal gold liposomes, compared with un-treated cells, colloidal gold liposome cannot export out of the cell. Conclusions:The uptake of liposomes in brain microvascular endothelial cells require clathrin's participation. The excretion of liposomes from brain microvascular endothelial cells require P-glycoprotein's participation. After colloidal gold liposome entering brain microvascular endothelial cells, it moves into the endoplasmic reticulum, Golgi apparatus and lysosomes in order. Finally colloi-dal gold liposome exports out of the cell.

  19. Biodistribution of boron after intravenous 4-dihydroxyborylphenylalanine-fructose (BPA-F) infusion in meningioma and schwannoma patients: A feasibility study for boron neutron capture therapy.

    Science.gov (United States)

    Kulvik, Martti; Kallio, Merja; Laakso, Juha; Vähätalo, Jyrki; Hermans, Raine; Järviluoma, Eija; Paetau, Anders; Rasilainen, Merja; Ruokonen, Inkeri; Seppälä, Matti; Jääskeläinen, Juha

    2015-12-01

    We studied the uptake of boron after 100 mg/kg BPA infusion in three meningioma and five schwannoma patients as a pre-BNCT feasibility study. With average tumour-to-whole blood boron concentrations of 2.5, we discuss why BNCT could, and probably should, be developed to treat severe forms of the studied tumours. However, analysing 72 tumour and 250 blood samples yielded another finding: the plasma-to-whole blood boron concentrations varied with time, suggesting that the assumed constant boron ratio of 1:1 between normal brain tissue and whole blood deserves re-assessment.

  20. Liposomal nanotransporter for targeted binding based on nucleic acid anchor system.

    Science.gov (United States)

    Nejdl, Lukas; Merlos Rodrigo, Miguel Angel; Kudr, Jiri; Ruttkay-Nedecky, Branislav; Konecna, Marie; Kopel, Pavel; Zitka, Ondrej; Hubalek, Jaromir; Kizek, Rene; Adam, Vojtech

    2014-02-01

    Microfluidic techniques have been developed intensively in recent years due to lower reagent consumption, faster analysis, and possibility of the integration of several analytical detectors into one chip. Electrochemical detectors are preferred in microfluidic systems, whereas liposomes can be used for amplification of the electrochemical signals. The aim of this study was to design a nanodevice for targeted anchoring of liposome as transport device. In this study, liposome with encapsulated Zn(II) was prepared. Further, gold nanoparticles were anchored onto the liposome surface allowing binding of thiol moiety-modified molecules (DNA). For targeted capturing of the transport device, DNA loops were used. DNA loops were represented by paramagnetic microparticles with oligo(DT)25 chain, on which a connecting DNA was bound. Capturing of transport device was subsequently done by hybridization to the loop. The individual steps were analyzed by electrochemistry and UV/Vis spectrometry. For detection of Zn(II) encapsulated in liposome, a microfluidic system was used. The study succeeded in demonstrating that liposome is suitable for the transport of Zn(II) and nucleic acids. Such transporter may be used for targeted binding using DNA anchor system.

  1. Probing the potential of apigenin liposomes in enhancing bacterial membrane perturbation and integrity loss.

    Science.gov (United States)

    Banerjee, Kacoli; Banerjee, Shubhadeep; Das, Subhayan; Mandal, Mahitosh

    2015-09-01

    Along with discovery of new antibacterial agents, it is important to develop novel drug delivery systems to effectively deliver drugs within bacterial cells for enhanced therapeutic activity. Liposomes have been extensively investigated as pharmaceutical carriers for improvement of therapeutic index of antimicrobial agents. The aim of this present study was to evaluate the antibacterial activity of free and liposomal formulation of apigenin, a plant based isoflavone and elucidate the mode of action. Distearoylphosphatidylcholine liposomes were prepared having nano-range particle size (104.3±1.8 nm), narrow particle distribution (0.204) and high encapsulation efficiency of apigenin (89.9±2.31%). Antibacterial activity of apigenin and efficacy of liposome-mediated apigenin delivery were determined from minimum inhibitory concentration values. Interaction studies using electron microscopy revealed adherence and fusion of liposomal apigenin with the bacteria causing membrane perturbation through reactive oxygen species generation which was evaluated by epi-fluorescence microscopy and fluorescence activated cell sorting. The interaction of apigenin liposomes with bacterial membrane increased intracellular drug concentration and thus, can be employed to deliver apigenin within cells to augment its antibacterial activity. Increased efficacy and hemocompatibility of this formulation paves way for future evaluation of underlying molecular mechanisms and in vivo testing for enhanced therapeutic effects.

  2. Phytosome and Liposome: The Beneficial Encapsulation Systems in Drug Delivery and Food Application

    Directory of Open Access Journals (Sweden)

    Nayyer Karimi

    2015-06-01

    Full Text Available Due to poor solubility in lipids, many of bioactive components (Nutraceutical materials show less bioactivity than optimal state in water solution. Phytosomes improve absorption and bioavailability of biomaterials. Liposomes, spherical shaped nanocarriers, were discovered in the 1960s by bangham. Due to their composition, variability and structural properties, liposomes and phytosomes are extremely versatile, leading to a large number of applications including pharmaceutical, cosmetics and food industrial fields. They are advanced forms of herbal formulations containing the bioactive phytoconstituents of herb extracts such as flavonoids, glycosides and terpenoids, which have good ability to transit from a hydrophilic environment into the lipid friendly environment of the outer cell membrane. They have better bioavailability and actions than the conventional herbal extracts containing dosage. Phytosome technology has increasing effect on the bioavailability of herbal extracts including ginkgo biloba, grape seed, green tea, milk thistle, ginseng, etc., and can be developed for various therapeutic uses or dietary supplements. Liposomes are composed of bilayer membranes, which are made of lipid molecules. They form when phospholipids are dispersed in aqueous media and exposed to high shear rates by using micro-fluidization or colloid mill. The mechanism for formation of liposomes is mainly the hydrophilic–hydrophobic interactions between phospholipids and water molecules. Here, we attempt to review the features of phytosomes and liposomes as well as their preparation methods and capacity in food and drug applications. Generally, it is believed that phytosomes and liposomes are suitable delivery systems for nutraceuticals, and can be widely used in food industry.

  3. Fast high-throughput screening of temoporfin-loaded liposomal formulations prepared by ethanol injection method.

    Science.gov (United States)

    Yang, Kewei; Delaney, Joseph T; Schubert, Ulrich S; Fahr, Alfred

    2012-03-01

    A new strategy for fast, convenient high-throughput screening of liposomal formulations was developed, utilizing the automation of the so-called ethanol-injection method. This strategy was illustrated by the preparation and screening of the liposomal formulation library of a potent second-generation photosensitizer, temoporfin. Numerous liposomal formulations were efficiently prepared using a pipetting robot, followed by automated size characterization, using a dynamic light scattering plate reader. Incorporation efficiency of temoporfin and zeta potential were also detected in selected cases. To optimize the formulation, different parameters were investigated, including lipid types, lipid concentration in injected ethanol, ratio of ethanol to aqueous solution, ratio of drug to lipid, and the addition of functional phospholipid. Step-by-step small liposomes were prepared with high incorporation efficiency. At last, an optimized formulation was obtained for each lipid in the following condition: 36.4 mg·mL(-1) lipid, 13.1 mg·mL(-1) mPEG(2000)-DSPE, and 1:4 ethanol:buffer ratio. These liposomes were unilamellar spheres, with a diameter of approximately 50 nm, and were very stable for over 20 weeks. The results illustrate this approach to be promising for fast high-throughput screening of liposomal formulations.

  4. Skin penetration behaviour of liposomes as a function of their composition.

    Science.gov (United States)

    Gillet, A; Lecomte, F; Hubert, P; Ducat, E; Evrard, B; Piel, G

    2011-09-01

    Deformable liposomes have been developed and evaluated as a novel topical and transdermal delivery system. Their mechanism of drug transport into and through the skin has been investigated but remains a much debated question. The present study concerns ex vivo diffusion experiments using pig ear skin in order to explain the penetration mechanism of classical and deformable liposomes. Classical and deformable vesicles containing betamethasone in the aqueous compartment through the use of cyclodextrin inclusion complexes were compared to vesicles encapsulating betamethasone in their lipid bilayer. Deformable liposomes contained sodium deoxycholate as the edge activator. Liposomes were characterised by their diameter, encapsulation efficiency, deformability, stability (in terms of change in diameter) and release of encapsulated drug. Ex vivo diffusion studies using Franz diffusion cells were performed. Confocal microscopy was performed to visualise the penetration of fluorescently labelled liposomes into the skin. This study showed that liposomes do not stay intact when they penetrate the deepest layers of the skin. Betamethasone is released from the vesicles after which free drug molecules can diffuse through the stratum corneum and partition into the viable skin tissue.

  5. Encapsulating contact allergens in liposomes, ethosomes, and polycaprolactone may affect their sensitizing properties.

    Science.gov (United States)

    Madsen, Jakob Torp; Vogel, Stefan; Johansen, Jeanne Duus; Andersen, Klaus Ejner

    2011-06-01

    Attempts to improve formulation of topical products are a continuing process and the development of micro- and nanovesicular systems as well as polymeric microparticles has led to marketing of topical drugs and cosmetics using these technologies. Encapsulation of some well-known contact allergens in ethanolic liposomes have been reported to enhance allergenicity compared with the allergens in similar vehicles without liposomes. The present report includes data on more sensitization studies using the mouse local lymph node assay with three contact allergens encapsulated in different dermal drug-delivery systems: liposomes, ethosomes, and polycaprolactone particles. The results show that the drug-delivery systems are not sensitizers in themselves. Encapsulating the hydrophilic contact allergen potassium dichromate in all three drug-delivery systems did not affect the sensitizing capacity of potassium dichromate compared with control solutions. However, encapsulating the lipophilic contact allergen dinitrochlorobenzene (DNCB) in polycaprolactone reduced the sensitizing capacity to 1211 ± 449 compared with liposomes (7602 ± 2658) and in acetone:olive oil (4:1) (5633 ± 666). The same trend was observed for encapsulating isoeugenol in polycaprolactone (1100 ± 406) compared with a formulation in acetone:olive oil (4491 ± 819) and in liposomes (3668 ± 950). Further, the size of DNCB-loaded liposomes did not affect the sensitizing properties. These results suggest that modern dermal drug-delivery systems may in some cases magnify or decrease the sensitizing capacity of the encapsulated contact allergen.

  6. Vincristine liposomal--INEX: lipid-encapsulated vincristine, onco TCS, transmembrane carrier system--vincristine, vincacine, vincristine sulfate liposomes for injection, VSLI.

    Science.gov (United States)

    2004-01-01

    INEX Pharmaceuticals is developing a liposomal formulation of vincristine [Onco TCS, vincacine, VSLI, Vincristine sulfate liposomes for injection] for the treatment of relapsed aggressive non-Hodgkin's lymphoma (NHL) and other cancers. It is being developed using INEX's proprietary drug-delivery technology platform called the transmembrane carrier systems (TCS), which enables the targeted intracellular delivery of various therapeutic agents. Liposomal vincristine is expected to have certain advantages over the existing standard preparation of vincristine because the use of TCS technology enables the vincristine to circulate in the blood for longer, accumulate in the tumour, and be released over an extended period of time at the tumour site. The application of TCS technology to any agent, including vincristine, has the potential to increase the efficacy and decrease the side effects of the agent. INEX decided in 1998 to focus on gaining approval for liposomal vincristine in the treatment of relapsed aggressive NHL because no standard therapy was approved for this indication. In 1999, liposomal vincristine was granted accelerated development status by the US FDA, which enables the FDA to approve it based on the surrogate endpoint of a single clinical trial. In addition, the FDA granted liposomal vincristine fast track status in August 2000. In April 2001, INEX and Elan Corporation formed a joint venture for the development and commercialisation of liposomal vincristine, with both companies contributing assets to the venture including worldwide rights to the product and intellectual property rights. The joint venture was called IE Oncology. However, in June 2002, Elan announced that it was going to focus its business strategy on three specific areas, which would not include cancer therapies. INEX announced it had regained 100% ownership of liposomal vincristine in April 2003, by reacquiring the 19.9% equity interest held by Elan and in addition retaining a fully paid

  7. Understanding boron through size-selected clusters: structure, chemical bonding, and fluxionality.

    Science.gov (United States)

    Sergeeva, Alina P; Popov, Ivan A; Piazza, Zachary A; Li, Wei-Li; Romanescu, Constantin; Wang, Lai-Sheng; Boldyrev, Alexander I

    2014-04-15

    Boron is an interesting element with unusual polymorphism. While three-dimensional (3D) structural motifs are prevalent in bulk boron, atomic boron clusters are found to have planar or quasi-planar structures, stabilized by localized two-center-two-electron (2c-2e) σ bonds on the periphery and delocalized multicenter-two-electron (nc-2e) bonds in both σ and π frameworks. Electron delocalization is a result of boron's electron deficiency and leads to fluxional behavior, which has been observed in B13(+) and B19(-). A unique capability of the in-plane rotation of the inner atoms against the periphery of the cluster in a chosen direction by employing circularly polarized infrared radiation has been suggested. Such fluxional behaviors in boron clusters are interesting and have been proposed as molecular Wankel motors. The concepts of aromaticity and antiaromaticity have been extended beyond organic chemistry to planar boron clusters. The validity of these concepts in understanding the electronic structures of boron clusters is evident in the striking similarities of the π-systems of planar boron clusters to those of polycyclic aromatic hydrocarbons, such as benzene, naphthalene, coronene, anthracene, or phenanthrene. Chemical bonding models developed for boron clusters not only allowed the rationalization of the stability of boron clusters but also lead to the design of novel metal-centered boron wheels with a record-setting planar coordination number of 10. The unprecedented highly coordinated borometallic molecular wheels provide insights into the interactions between transition metals and boron and expand the frontier of boron chemistry. Another interesting feature discovered through cluster studies is boron transmutation. Even though it is well-known that B(-), formed by adding one electron to boron, is isoelectronic to carbon, cluster studies have considerably expanded the possibilities of new structures and new materials using the B(-)/C analogy. It is

  8. BCM6: New Generation of Boron Meter

    Energy Technology Data Exchange (ETDEWEB)

    Pirat, P. [Rolls-Royce Civil Nuclear SAS (France)

    2010-07-01

    Full text of publication follows: Rolls-Royce has developed a new generation of boron meter, based on more than 30 years of experience. The Rolls-Royce BCM6 boron meter provides Nuclear Power Plant (NPP) operators with the boron concentration of the primary circuit. The meter provides continuous and safe measurements with no manual sampling and no human contact. In this paper, technical features, advantages and customer benefits of the use of the new generation of Rolls-Royce BCM6 boron meter will be detailed. Values and associated alarms are provides over different media: 4-20 mA outputs, relays, displays in the main control room and in the chemical lab, and digital links. A special alarm avoids unexpected homogeneous dilution of the primary circuit, which is a critical operational parameter. The Rolls-Royce BCM6 boron meter is fully configurable over a set of parameters allowing adaptation to customer needs. It has a differential capability, thus eliminating neutronic noise and keeping measurements accurate, even in the case of fuel clad rupture. Measurements are accurate, reliable, and have a quick response time. Equipment meets state-of-the-art qualification requests. Designed in 2008, the BCM6 boron meter is the newest equipment of Rolls-Royce boron meters product line. It has been chosen to equip the French EPR NPP and complies with the state-of-the-art of the technology. Rolls-Royce has more than 30 years of experience in Instrumentation and Controls with more than 75 NPP units operating worldwide. All of this experience return has been put in this new generation of equipment to provide the customer with the best operation. About Rolls-Royce Rolls-Royce is a global business providing integrated power systems for use on land, at sea and in the air. The Group has a balanced business portfolio with leading market positions. Rolls-Royce has a broad range of civil nuclear expertise, including work related to licensing and safety reviews, engineering design

  9. β-Rhombohedral Boron: At the Crossroads of the Chemistry of Boron and the Physics of Frustration [Boron: a frustrated element

    Energy Technology Data Exchange (ETDEWEB)

    Ogitsu, Tadashi [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Schwegler, Eric [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Galli, Giulia [Univ. of California, Davis, CA (United States)

    2013-05-08

    In the periodic table boron occupies a peculiar, crossover position: on the first row, it is surrounded by metal forming elements on the left and by non-metals on the right. In addition, it is the only non-metal of the third column. Therefore it is perhaps not surprising that the crystallographic structure and topology of its stable allotrope at room temperature (β-boron) are not shared by any other element, and are extremely complex. The formidable intricacy of β- boron, with interconnecting icosahedra, partially occupied sites, and an unusually large number of atoms per unit cell (more than 300) has been known for more than 40 years. Nevertheless boron remains the only element purified in significant quantities whose ground state geometry has not been completely determined by experiments. However theoretical progress reported in the last decade has shed light on numerous properties of elemental boron, leading to a thorough characterization of its structure at ambient conditions, as well as of its electronic and thermodynamic properties. This review discusses in detail the properties of β-boron, as inferred from experiments and the ab-initio theories developed in the last decade.

  10. Hugoniot equation of state and dynamic strength of boron carbide

    Energy Technology Data Exchange (ETDEWEB)

    Grady, Dennis E. [Applied Research Associates, Southwest Division, 4300 San Mateo Blvd NE, A-220, Albuquerque, New Mexico 87110-129 (United States)

    2015-04-28

    Boron carbide ceramics have been particularly problematic in attempts to develop adequate constitutive model descriptions for purposes of analysis of dynamic response in the shock and impact environment. Dynamic strength properties of boron carbide ceramic differ uniquely from comparable ceramics. Furthermore, boron carbide is suspected, but not definitely shown, to undergoing polymorphic phase transformation under shock compression. In the present paper, shock-wave compression measurements conducted over the past 40 years are assessed for the purpose of achieving improved understanding of the dynamic equation of state and strength of boron carbide. In particular, attention is focused on the often ignored Los Alamos National Laboratory (LANL) Hugoniot measurements performed on porous sintered boron carbide ceramic. The LANL data are shown to exhibit two compression anomalies on the shock Hugoniot within the range of 20–60 GPa that may relate to crystallographic structure transitions. More recent molecular dynamics simulations on the compressibility of the boron carbide crystal lattice reveal compression transitions that bear similarities to the LANL Hugoniot results. The same Hugoniot data are complemented with dynamic isentropic compression data for boron carbide extracted from Hugoniot measurements on boron carbide and copper granular mixtures. Other Hugoniot measurements, however, performed on near-full-density boron carbide ceramic differ markedly from the LANL Hugoniot data. These later data exhibit markedly less compressibility and tend not to show comparable anomalies in compressibility. Alternative Hugoniot anomalies, however, are exhibited by the near-full-density data. Experimental uncertainty, Hugoniot strength, and phase transformation physics are all possible explanations for the observed discrepancies. It is reasoned that experimental uncertainty and Hugoniot strength are not likely explanations for the observed differences. The notable

  11. Hugoniot equation of state and dynamic strength of boron carbide

    Science.gov (United States)

    Grady, Dennis E.

    2015-04-01

    Boron carbide ceramics have been particularly problematic in attempts to develop adequate constitutive model descriptions for purposes of analysis of dynamic response in the shock and impact environment. Dynamic strength properties of boron carbide ceramic differ uniquely from comparable ceramics. Furthermore, boron carbide is suspected, but not definitely shown, to undergoing polymorphic phase transformation under shock compression. In the present paper, shock-wave compression measurements conducted over the past 40 years are assessed for the purpose of achieving improved understanding of the dynamic equation of state and strength of boron carbide. In particular, attention is focused on the often ignored Los Alamos National Laboratory (LANL) Hugoniot measurements performed on porous sintered boron carbide ceramic. The LANL data are shown to exhibit two compression anomalies on the shock Hugoniot within the range of 20-60 GPa that may relate to crystallographic structure transitions. More recent molecular dynamics simulations on the compressibility of the boron carbide crystal lattice reveal compression transitions that bear similarities to the LANL Hugoniot results. The same Hugoniot data are complemented with dynamic isentropic compression data for boron carbide extracted from Hugoniot measurements on boron carbide and copper granular mixtures. Other Hugoniot measurements, however, performed on near-full-density boron carbide ceramic differ markedly from the LANL Hugoniot data. These later data exhibit markedly less compressibility and tend not to show comparable anomalies in compressibility. Alternative Hugoniot anomalies, however, are exhibited by the near-full-density data. Experimental uncertainty, Hugoniot strength, and phase transformation physics are all possible explanations for the observed discrepancies. It is reasoned that experimental uncertainty and Hugoniot strength are not likely explanations for the observed differences. The notable mechanistic

  12. Effect of Boron Content on the Microstructure and Magnetic Properties of Non-oriented Electrical Steels

    Institute of Scientific and Technical Information of China (English)

    WAN Yong; CHEN Weiqing

    2015-01-01

    The effects of boron content in the range of 0-0.0082 wt%, on the inclusion type, microstructure, texture and magnetic properties of non-oriented electrical steels have been studied. Afterfi nal annealing, the addition of excess boron(w(Bt)>0.004 1 wt%) led to the formation of Fe2B particles. As boron content increased, grain size increased and reached a maximum in steel with 0.004 1 wt% boron. Furthermore, steel containing 0.004 1 wt% boron had the strongest {100}fi ber texture, Goss texture and the weakest {111}fi ber texture among thefi ve tested steels. Flux densityfi rstly rapidly increased and then suddenly decreased with increasing boron content and reached a maximum in steel with 0.004 1 wt% boron. Conversely, core lossfi rst sharply decreased and then abruptly increased with the increase of boron content and reached a minimum in steel containing 0.004 1 wt% boron. Steel containing 0.004 1 wt% boron obtained the best magnetic properties, predominantly through the development of optimum grain size and favorable texture.

  13. Recent Advances in Boron-Containing Conjugated Porous Polymers

    Directory of Open Access Journals (Sweden)

    Feng Qiu

    2016-05-01

    Full Text Available Porous polymers, integrating the advantages of porous materials and conventional polymers, have been well developed and exhibited tremendous attention in the fields of material, chemistry and biology. Of these, boron-containing conjugated porous polymers, featuring tunable geometric structures, unique Lewis acid boron centers and very rich physical properties, such as high specific surface, chargeable scaffold, strong photoluminescence and intramolecular charge transfer, have emerged as one of the most promising functional materials for optoelectronics, catalysis and sensing, etc. Furthermore, upon thermal treatment, some of them can be effectively converted to boron-doped porous carbon materials with good electrochemical performance in energy storage and conversion, extensively enlarging the applicable scope of such kinds of polymers. In this review, the synthetic approaches, structure analyses and various applications of the boron-containing conjugated porous polymers reported very recently are summarized.

  14. Understanding Boron through Size-Selected Clusters: Structure, Chemical Bonding, and Fluxionality

    Energy Technology Data Exchange (ETDEWEB)

    Sergeeva, Alina P.; Popov, Ivan A.; Piazza, Zachary A.; Li, Wei-Li; Romanescu, Constantin; Wang, Lai S.; Boldyrev, Alexander I.

    2014-04-15

    Conspectus Boron is an interesting element with unusual polymorphism. While three-dimensional (3D) structural motifs are prevalent in bulk boron, atomic boron clusters are found to have planar or quasi-planar structures, stabilized by localized two-center–two-electron (2c–2e) σ bonds on the periphery and delocalized multicenter–two-electron (nc–2e) bonds in both σ and π frameworks. Electron delocalization is a result of boron’s electron deficiency and leads to fluxional behavior, which has been observed in B13+ and B19–. A unique capability of the in-plane rotation of the inner atoms against the periphery of the cluster in a chosen direction by employing circularly polarized infrared radiation has been suggested. Such fluxional behaviors in boron clusters are interesting and have been proposed as molecular Wankel motors. The concepts of aromaticity and antiaromaticity have been extended beyond organic chemistry to planar boron clusters. The validity of these concepts in understanding the electronic structures of boron clusters is evident in the striking similarities of the π-systems of planar boron clusters to those of polycyclic aromatic hydrocarbons, such as benzene, naphthalene, coronene, anthracene, or phenanthrene. Chemical bonding models developed for boron clusters not only allowed the rationalization of the stability of boron clusters but also lead to the design of novel metal-centered boron wheels with a record-setting planar coordination number of 10. The unprecedented highly coordinated borometallic molecular wheels provide insights into the interactions between transition metals and boron and expand the frontier of boron chemistry. Another interesting feature discovered through cluster studies is boron transmutation. Even though it is well-known that B–, formed by adding one electron to boron, is isoelectronic to carbon, cluster studies have considerably expanded the possibilities of new structures and new materials using the B

  15. Liposomal anticancer therapy: pharmacokinetic and clinical aspects.

    Science.gov (United States)

    Di Paolo, A

    2004-11-01

    Liposomes, which are vesicles composed of a phospholipid bilayer surrounding an aqueous milieu, represent a new strategy for anticancer drug delivery. Extravasation and accumulation of liposomal drugs within neoplastic tissues are possible because of the leaky vasculature and scarce lymphatic vessels of tumours (the enhanced permeability and retention effect). Furthermore, liposomal chemotherapeutic agents display distinctive pharmacokinetic characteristics, because they possess longer elimination half-lives, reduced clearance and smaller volume of distribution with respect to corresponding free drugs. Taken together, these features lead to highest levels of cytotoxic agents in tumours, as demonstrated in preclinical models and clinical trials, whereas healthy tissues are spared from toxicity. In fact, liposomal drugs (i.e., doxorubicin), alone or in combination with other cytotoxic agents, lead to improved clinical effectiveness and ameliorated toxicity profile with respect to corresponding free drugs when they are used for the treatment of metastatic breast and ovarian cancers, and Kaposi's sarcoma.

  16. Functionalized boron nitride nanotubes

    Science.gov (United States)

    Sainsbury, Toby; Ikuno, Takashi; Zettl, Alexander K

    2014-04-22

    A plasma treatment has been used to modify the surface of BNNTs. In one example, the surface of the BNNT has been modified using ammonia plasma to include amine functional groups. Amine functionalization allows BNNTs to be soluble in chloroform, which had not been possible previously. Further functionalization of amine-functionalized BNNTs with thiol-terminated organic molecules has also been demonstrated. Gold nanoparticles have been self-assembled at the surface of both amine- and thiol-functionalized boron nitride Nanotubes (BNNTs) in solution. This approach constitutes a basis for the preparation of highly functionalized BNNTs and for their utilization as nanoscale templates for assembly and integration with other nanoscale materials.

  17. Active loading of gemcitabine into liposomes

    OpenAIRE

    Møkleby, Tormund Aasjord

    2009-01-01

    Gemcitabine is a well established anticancer compound, and is in use today against several types of cancers. Gemcitabine has a short half life. Formulations of gemcitabine containing liposomes could extend it's half life, thereby maybe improving its effectiveness. Also, liposomes in the smaller size range have an advantage when it comes to treating cancer. They accumulate at the site of the tumor, and stay there for a longer time than it would have done in normal tissue(Massing and Fuxius 2...

  18. Scale-Up of Liposome Manufacturing

    OpenAIRE

    Wiggenhorn, Michael

    2007-01-01

    The study provides a comprehensive overview on different stabilization techniques for liposomal formulations. The selection of the appropriate technology for a particular formulation can thereby be based on several considerations. If free flowable particulate bulk material is desired the spraying-technologies are preferred over lyophilization. Another advantage of spraying-based technologies is the possibility to combine the liposome formation step and the drying step within the same process....

  19. Liposomal Systems as Nanocarriers for the Antiviral Agent Ivermectin

    Directory of Open Access Journals (Sweden)

    Romina Croci

    2016-01-01

    Full Text Available RNA virus infections can lead to the onset of severe diseases such as fever with haemorrhage, multiorgan failure, and mortality. The emergence and reemergence of RNA viruses continue to pose a significant public health threat worldwide with particular attention to the increasing incidence of flaviviruses, among others Dengue, West Nile Virus, and Yellow Fever viruses. Development of new and potent antivirals is thus urgently needed. Ivermectin, an already known antihelminthic drug, has shown potent effects in vitro on Flavivirus helicase, with EC50 values in the subnanomolar range for Yellow Fever and submicromolar EC50 for Dengue Fever, Japanese encephalitis, and tick-borne encephalitis viruses. However ivermectin is hampered in its application by pharmacokinetic problems (little solubility and high cytotoxicity. To overcome such problems we engineered different compositions of liposomes as ivermectin carriers characterizing and testing them on several cell lines for cytotoxicity. The engineered liposomes were less cytotoxic than ivermectin alone and they showed a significant increase of the antiviral activity in all the Dengue stains tested (1, 2, and S221. In the current study ivermectin is confirmed to be an effective potential antiviral and liposomes, as drug carriers, are shown to modulate the drug activity. All together the results represent a promising starting point for future improvement of ivermectin as antiviral and its delivery.

  20. Physico-chemical characterization of liposomes and drug substance-liposome interactions in pharmaceutics using capillary electrophoresis and electrokinetic chromatography

    DEFF Research Database (Denmark)

    Franzen, Ulrik; Østergaard, Jesper

    2012-01-01

    Liposomes are self-assembled phospholipid vesicles and have numerous research and therapeutic applications. In the pharmaceutical and biomedical sciences liposomes find use as models of biological membranes, partitioning medium and as drug carriers. The present review addresses the use of capillary...... electrophoresis and liposome electrokinetic chromatography for the characterization of liposomes in a pharmaceutical context. Capillary electrophoretic techniques have been used for the measurement of electrophoretic mobility, which provides information on liposome surface charge, size and membrane permeability...... of liposomes. The use of liposome electrokinetic chromatography and capillary electrophoresis for determination of liposome/water partitioning and characterization of drug-liposome interactions is reviewed. A number of studies indicate that capillary electrophoresis may have a role in the characterization...

  1. Chronic boron exposure and human semen parameters.

    Science.gov (United States)

    Robbins, Wendie A; Xun, Lin; Jia, Juan; Kennedy, Nola; Elashoff, David A; Ping, Liu

    2010-04-01

    Boron found as borates in soil, food, and water has important industrial and medical applications. A panel reviewing NTP reproductive toxicants identified boric acid as high priority for occupational studies to determine safe versus adverse reproductive effects. To address this, we collected boron exposure/dose measures in workplace inhalable dust, dietary food/fluids, blood, semen, and urine from boron workers and two comparison worker groups (n=192) over three months and determined correlations between boron and semen parameters (total sperm count, sperm concentration, motility, morphology, DNA breakage, apoptosis and aneuploidy). Blood boron averaged 499.2 ppb for boron workers, 96.1 and 47.9 ppb for workers from high and low environmental boron areas (pBoron concentrated in seminal fluid. No significant correlations were found between blood or urine boron and adverse semen parameters. Exposures did not reach those causing adverse effects published in animal toxicology work but exceeded those previously published for boron occupational groups.

  2. Poly(ethylene glycol) on the liposome surface: on the mechanism of polymer-coated liposome longevity.

    Science.gov (United States)

    Torchilin, V P; Omelyanenko, V G; Papisov, M I; Bogdanov, A A; Trubetskoy, V S; Herron, J N; Gentry, C A

    1994-10-12

    The hypothetical model is built explaining the molecular mechanism of protective action of poly(ethylene glycol) on liposomes in vivo. The protective layer of the polymer on the liposome surface is considered as a statistical 'cloud' of polymer possible conformations in solution. Computer simulation was used to demonstrate that relatively a small number of liposome-grafted molecules of hydrophilic and flexible polymer can create a dense protective conformational cloud over the liposome surface preventing opsonizing protein molecules from contacting liposome. A more rigid polymer fails to form this dense protective cloud, even when hydrophilic. Computer simulation was also used to reveal possible heterogeneity of reactive sites on a polymer-coated liposome surface, and to estimate the optimal polymer-to-lipid ratio for efficient liposome protection. Experiments have been performed with the quenching of liposome-associated fluorescent label (nitrobenzoxadiazole or fluorescein) with protein (rhodamine-ovalbumin or anti-fluorescein antibody) from solution. It was shown that poly(ethylene glycol) grafting to liposomes hinders protein interaction with the liposome surface, whereas liposome-grafted dextran (more rigid polymer) in similar quantities does not affect protein-liposome interaction. Highly-reactive and low-reactive populations of chemically identical reactive sites have been found on polymer-coated liposomes. Experimental data satisfactory confirm the suggested mechanism for the longevity of polymer-modified liposome.

  3. Hemorrhage in mouse tumors induced by dodecaborate cluster lipids intended for boron neutron capture therapy

    Directory of Open Access Journals (Sweden)

    Schaffran T

    2014-07-01

    Full Text Available Tanja Schaffran,1 Nan Jiang,1 Markus Bergmann,2,3 Ekkehard Küstermann,4 Regine Süss,5 Rolf Schubert,5 Franz M Wagner,6 Doaa Awad,7 Detlef Gabel1,2,8 1Department of Chemistry, University of Bremen, 2Institute of Neuropathology, Klinikum Bremen-Mitte; 3Cooperative Center Medicine, University of Bremen, 4“In-vivo-MR” AG, FB2, University of Bremen, Bremen, 5Pharmaceutical Technology, University of Freiburg, Freiburg im Breisgau, 6Forschungsneutronenquelle Heinz Maier-Leibnitz (FRM II, Technische Unversitaet Muenchen, Garching, Germany; 7Department of Biochemistry, Alexandria University, Alexandria, Egypt; 8School of Engineering and Science, Jacobs University Bremen, Bremen, Germany Abstract: The potential of boron-containing lipids with three different structures, which were intended for use in boron neutron capture therapy, was investigated. All three types of boron lipids contained the anionic dodecaborate cluster as the headgroup. Their effects on two different tumor models in mice following intravenous injection were tested; for this, liposomes with boron lipid, distearoyl phosphatidylcholine, and cholesterol as helper lipids, and containing a polyethylene glycol lipid for steric protection, were administered intravenously into tumor-bearing mice (C3H mice for SCCVII squamous cell carcinoma and BALB/c mice for CT26/WT colon carcinoma. With the exception of one lipid (B-THF-14, the lipids were well tolerated, and no other animal was lost due to systemic toxicity. The lipid which led to death was not found to be much more toxic in cell culture than the other boron lipids. All of the lipids that were well tolerated showed hemorrhage in both tumor models within a few hours after administration. The hemorrhage could be seen by in vivo magnetic resonance and histology, and was found to occur within a few hours. The degree of hemorrhage depended on the amount of boron administered and on the tumor model. The observed unwanted effect of the lipids

  4. Bioactive constituents in liposomes incorporated in orange juice as new functional food: thermal stability, rheological and organoleptic properties.

    Science.gov (United States)

    Marsanasco, Marina; Piotrkowski, Bárbara; Calabró, Valeria; Del Valle Alonso, Silvia; Chiaramoni, Nadia S

    2015-12-01

    Liposomes were developed with bioactive constituents (omega-3, omega-6, tocopherol) incorporated in acid food. They were made of soy phosphatidylcholine (SPC) allowing the encapsulation of antioxidant vitamin C (VC) and tocopherol. Stearic acid (SA) or calcium stearate (CaS) was added as a bilayer stabilizer. The structural and oxidative stability of the liposomes were studied considering the heat effect of pasteurization. Size was analyzed by light scattering; shape and structure were studied by optical and transmission electron microscopy, respectively. Membrane packing was studied with merocyanine 540. Surface charge and oxidative stability were analyzed by zeta potential and ORAC method, respectively. The liposomes showed significant stability in all of the parameters mentioned above and an important protective effect over thermolabile VC. To confirm their applicability in food, the rheological behavior and a sensory evaluation of liposomes with vitamin C and bioactive constituents were studied. The sensory evaluation of liposomes in orange juice was performed by the overall acceptability and triangular tests with 40 and 78 potential consumers, respectively. The incorporation of all liposomal formulation did not change the acceptability of orange juice. Noteworthy, SPC and SPC:SA systems had rheological behavior similar to a Newtonian fluid whereas that SPC:CaS presented a pseudoplastic one, both considered excellent for larger scale production. From all the obtained results, we can conclude that these liposomal formulations are suitable for food industry applications, incorporating bioactive constituents and generating functional orange juice that conserves its bioactivity after pasteurization.

  5. Liposomes containing glycocholate as potential oral insulin delivery systems: preparation, in vitro characterization, and improved protection against enzymatic degradation

    Science.gov (United States)

    Niu, Mengmeng; Lu, Yi; Hovgaard, Lars; Wu, Wei

    2011-01-01

    Background: Oral delivery of insulin is challenging and must overcome the barriers of gastric and enzymatic degradation as well as low permeation across the intestinal epithelium. The present study aimed to develop a liposomal delivery system containing glycocholate as an enzyme inhibitor and permeation enhancer for oral insulin delivery. Methods: Liposomes containing sodium glycocholate were prepared by a reversed-phase evaporation method followed by homogenization. The particle size and entrapment efficiency of recombinant human insulin (rhINS)-loaded sodium glycocholate liposomes can be easily adjusted by tuning the homogenization parameters, phospholipid:sodium glycocholate ratio, insulin:phospholipid ratio, water:ether volume ratio, interior water phase pH, and the hydration buffer pH. Results: The optimal formulation showed an insulin entrapment efficiency of 30% ± 2% and a particle size of 154 ± 18 nm. A conformational study by circular dichroism spectroscopy and a bioactivity study confirmed the preserved integrity of rhINS against preparative stress. Transmission electron micrographs revealed a nearly spherical and deformed structure with discernable lamella for sodium glycocholate liposomes. Sodium glycocholate liposomes showed better protection of insulin against enzymatic degradation by pepsin, trypsin, and α-chymotrypsin than liposomes containing the bile salt counterparts of sodium taurocholate and sodium deoxycholate. Conclusion: Sodium glycocholate liposomes showed promising in vitro characteristics and have the potential to be able to deliver insulin orally. PMID:21822379

  6. Cardiovascular and behavioral effects produced by administration of liposome-entrapped GABA into the rat central nervous system.

    Science.gov (United States)

    Vaz, G C; Bahia, A P C O; de Figueiredo Müller-Ribeiro, F C; Xavier, C H; Patel, K P; Santos, R A S; Moreira, F A; Frézard, F; Fontes, M A P

    2015-01-29

    Liposomes are nanosystems that allow a sustained release of entrapped substances. Gamma-aminobutyric acid (GABA) is the most prevalent inhibitory neurotransmitter of the central nervous system (CNS). We developed a liposomal formulation of GABA for application in long-term CNS functional studies. Two days after liposome-entrapped GABA was injected intracerebroventricularly (ICV), Wistar rats were submitted to the following evaluations: (1) changes in mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA) to ICV injection of bicuculline methiodide (BMI) in anesthetized rats; (2) changes in cardiovascular reactivity to air jet stress in conscious rats; and (3) anxiety-like behavior in conscious rats. GABA and saline-containing pegylated liposomes were prepared with a mean diameter of 200 nm. Rats with implanted cannulas targeted to lateral cerebral ventricle (n = 5-8/group) received either GABA solution (GS), empty liposomes (EL) or GABA-containing liposomes (GL). Following (48 h) central microinjection (2 μL, 0.09 M and 99 g/L) of liposomes, animals were submitted to the different protocols. Animals that received GL demonstrated attenuated response of RSNA to BMI microinjection (GS 48 ± 9, EL 43 ± 9, GL 11 ± 8%; P nervous system.

  7. Pegylated liposomal doxorubicin in ovarian cancer

    Directory of Open Access Journals (Sweden)

    Robert Strother

    2009-08-01

    Full Text Available Robert Strother1,2, Daniela Matei1–51Department of Medicine, 2Indiana University Melvin and Bren Simon Cancer Center, 3Department of Obstetrics and Gynecology, 4Department of Biochemistry and Molecular Biology, 5VA Roudebush Hospital Indiana University School of Medicine, 535 Barnhill Drive, Indianapolis, IN, 46202Abstract: The encapsulation of doxorubicin in a pegylated liposomal matrix led to a reformulated agent with a different toxicity profile and improved clinical utility. Liposomal doxorubicin is devoid of the cardiac toxicity associated with doxorubicin, but is associated with predictable muco-cutaneous toxicity. The liposomal formulation leads to improved delivery to the target tumor tissue, allowing enhanced uptake by cancer cells. These properties translate into clinical utility in recurrent ovarian cancer as demonstrated by phase II and III trials, this proven clinical efficacy leading to FDA approval in second-line therapy for ovarian cancer. New combinations with cytotoxics, in particular with carboplatin, have demonstrated an acceptable toxicity profile and clinical utility in platinum-sensitive ovarian cancer. A favorable toxicity profile renders liposomal doxorubicin an ideal partner for combination regimens with other cytotoxics, and more recently with biological agents. Such combinations are the subject of ongoing clinical trials.Keywords: ovarian cancer, doxorubicin, liposomes, pegylated liposomal doxorubicin

  8. Non inflammatory boronate based glucose-responsive insulin delivery systems.

    Directory of Open Access Journals (Sweden)

    Indrani Dasgupta

    Full Text Available Boronic acids, known to bind diols, were screened to identify non-inflammatory cross-linkers for the preparation of glucose sensitive and insulin releasing agglomerates of liposomes (Agglomerated Vesicle Technology-AVT. This was done in order to select a suitable replacement for the previously used cross-linker, ConcanavalinA (ConA, a lectin known to have both toxic and inflammatory effects in vivo. Lead-compounds were selected from screens that involved testing for inflammatory potential, cytotoxicity and glucose-binding. These were then conjugated to insulin-encapsulating nanoparticles and agglomerated via sugar-boronate ester linkages to form AVTs. In vitro, the particles demonstrated triggered release of insulin upon exposure to physiologically relevant concentrations of glucose (10 mmoles/L-40 mmoles/L. The agglomerates were also shown to be responsive to multiple spikes in glucose levels over several hours, releasing insulin at a rate defined by the concentration of the glucose trigger.

  9. Liposomal drug delivery system from laboratory to clinic

    Directory of Open Access Journals (Sweden)

    Kshirsagar N

    2005-01-01

    Full Text Available The main objective of drug delivery systems is to deliver a drug effectively, specifically to the site of action and to achieve greater efficacy and minimise the toxic effects compared to conventional drugs. Amongst various carrier systems, liposomes have generated a great interest because of their versatility. Liposomes are vesicular concentric bilayered structures, which are biocompatible, biodegradable and nonimmumnogenic. They can control the delivery of drugs by targeting the drug to the site of action or by site avoidance drug delivery or by prolonged circulation of drugs. Amphotericin B (Amp B remains the drug of choice in most systemic mycoses and also as a second line treatment for Kala azar. However, its toxic effects often limit its use. Although the liposome delivery system has been tried for several drugs, only a few have been used in patients due to the slow development of necessary large-scale pharmaceutical procedures. This paper reviews the development of the technique for liposomal Amphotericin B (L-Amp-LRC-1, FungisomeTM drug delivery system in our laboratory in collaboration with the department of Biochemistry, Delhi University in India and proving the safety and efficacy of this preparation in clinical practice. It also attempts to compare the efficacy and benefits of our product for Indian patients with those of similar products and it includes facts from the publications that flowed from our work. As compared to conventional Amp B, Fungisome is infused over a much shorter period requiring a smaller volume and no premedication. It was found to be safe in patients who had developed serious unacceptable toxicity with conventional Amp B. In renal transplant patients, Fungisome did not produce any nephrotoxicity. Fungisome is effective in fungal infections resistant to fluconazole, conventional Amp B and in virgin and resistant cases of visceral leishmaniasis. The cost of any drug is of great significance, especially in India

  10. Application of liposomal technologies for delivery of platinum analogs in oncology

    Directory of Open Access Journals (Sweden)

    Liu D

    2013-08-01

    Full Text Available Demin Liu1, Chunbai He1, Andrew Z Wang2, Wenbin Lin1 1Department of Chemistry, University of Chicago, Chicago, IL, USA; 2Laboratory of Nano- and Translational Medicine, Department of Radiation Oncology, and Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC, USA Abstract: Platinum-based chemotherapy, such as cisplatin, oxaliplatin, and carboplatin, is one of the most widely utilized classes of cancer therapeutics. While highly effective, the clinical applications of platinum-based drugs are limited by their toxicity profiles as well as suboptimal pharmacokinetic properties. Therefore, one of the key research areas in oncology has been to develop novel platinum analog drugs and engineer new platinum drug formulations to improve the therapeutic ratio further. Such efforts have led to the development of platinum analogs including nedaplatin, heptaplatin, and lobaplatin. Moreover, reformulating platinum drugs using liposomes has resulted in the development of L-NDPP (Aroplatin™, SPI-77, Lipoplatin™, Lipoxal™, and LiPlaCis®. Liposomes possess several attractive biological activities, including biocompatibility, high drug loading, and improved pharmacokinetics, that are well suited for platinum drug delivery. In this review, we discuss the various platinum drugs and their delivery using liposome-based drug delivery vehicles. We compare and contrast the different liposome platforms as well as speculate on the future of platinum drug delivery research. Keywords: liposome, platinum analog, drug delivery, cancer

  11. Boron Neutron Capture Therapy (BCNT) for the Treatment of Liver Metastases: Biodistribution Studies of Boron Compounds in an Experimental Model

    Energy Technology Data Exchange (ETDEWEB)

    Marcela A. Garabalino; Andrea Monti Hughes; Ana J. Molinari; Elisa M. Heber; Emiliano C. C. Pozzi; Maria E. Itoiz; Veronica A. Trivillin; Amanda E. Schwint; Jorge E. Cardoso; Lucas L. Colombo; Susana Nievas; David W. Nigg; Romina F. Aromando

    2011-03-01

    Abstract We previously demonstrated the therapeutic efficacy of different boron neutron capture therapy (BNCT) protocols in an experimental model of oral cancer. BNCT is based on the selective accumulation of 10B carriers in a tumor followed by neutron irradiation. Within the context of exploring the potential therapeutic efficacy of BNCT for the treatment of liver metastases, the aim of the present study was to perform boron biodistribution studies in an experimental model of liver metastases in rats. Different boron compounds and administration conditions were assayed to determine which administration protocols would potentially be therapeutically useful in in vivo BNCT studies at the RA-3 nuclear reactor. A total of 70 BDIX rats were inoculated in the liver with syngeneic colon cancer cells DHD/K12/TRb to induce the development of subcapsular tumor nodules. Fourteen days post-inoculation, the animals were used for biodistribution studies. We evaluated a total of 11 administration protocols for the boron compounds boronophenylalanine (BPA) and GB-10 (Na210B10H10), alone or combined at different dose levels and employing different administration routes. Tumor, normal tissue, and blood samples were processed for boron measurement by atomic emission spectroscopy. Six protocols proved potentially useful for BNCT studies in terms of absolute boron concentration in tumor and preferential uptake of boron by tumor tissue. Boron concentration values in tumor and normal tissues in the liver metastases model show it would be feasible to reach therapeutic BNCT doses in tumor without exceeding radiotolerance in normal tissue at the thermal neutron facility at RA-3.

  12. Boron-10 ABUNCL Models of Fuel Testing

    Energy Technology Data Exchange (ETDEWEB)

    Siciliano, Edward R.; Lintereur, Azaree T.; Kouzes, Richard T.; Ely, James H.

    2013-10-01

    The Department of Energy Office of Nuclear Safeguards and Security (NA-241) is supporting the project Coincidence Counting With Boron-Based Alternative Neutron Detection Technology at Pacific Northwest National Laboratory (PNNL) for the development of a 3He proportional counter alternative neutron coincidence counter. The goal of this project is to design, build and demonstrate a system based upon 10B-lined proportional tubes in a configuration typical for 3He-based coincidence counter applications. This report provides results from MCNP simulations of the General Electric Reuter-Stokes Alternative Boron-Based Uranium Neutron Coincidence Collar (ABUNCL) active configuration model with fuel pins previously measured at Los Alamos National Laboratory. A comparison of the GE-ABUNCL simulations and simulations of 3He based UNCL-II active counter (the system for which the GE-ABUNCL was targeted to replace) with the same fuel pin assemblies is also provided.

  13. Influence of particle size on drug delivery to rat alveolar macrophages following pulmonary administration of ciprofloxacin incorporated into liposomes.

    Science.gov (United States)

    Chono, Sumio; Tanino, Tomoharu; Seki, Toshinobu; Morimoto, Kazuhiro

    2006-09-01

    In order to confirm the efficacy of ciprofloxacin (CPFX) incorporated into liposomes (CPFX-liposomes) for treatment of respiratory intracellular parasite infections, the influence of particle size on drug delivery to rat alveolar macrophages (AMs) following pulmonary administration of CPFX-liposomes was investigated. CPFX-liposomes were prepared with hydrogenated soybean phosphatidylcholine (HSPC), cholesterol (CH) and dicetylphosphate (DCP) in a lipid molar ratio of 7/2/1 by the hydration method and then adjusted to five different particle sizes (100, 200, 400, 1000 and 2000 nm). In the pharmacokinetic experiment, the delivery efficiency of CPFX to rat AMs following pulmonary administration of CPFX-liposomes increased with the increase in the particle size over the range 100-1000 nm and became constant at over 1000 nm. The concentrations of CPFX in rat AMs until 24 h after pulmonary administration of CPFX-liposomes with a particle size of 1000 nm were higher than the minimum inhibitory concentration of CPFX against various intracellular parasites. In a cytotoxic test, no release of lactate dehydrogenase (LDH) from rat lung tissues by pulmonary administration of CPFX-liposomes with a particle size of 1000 nm was observed. These findings indicate that efficient delivery of CPFX to AMs by CPFX-liposomes with a particle size of 1000 nm induces an excellent antibacterial effect without any cytotoxic effects on lung tissues. Therefore, CPFX-liposomes may be useful in the development of drug delivery systems for the treatment of respiratory infections caused by intracellular parasites, such as Mycobacterium tuberculosis, Chlamydia pneumoniae and Listeria monocytogenes.

  14. Rapid accurate isotopic measurements on boron in boric acid and boron carbide.

    Science.gov (United States)

    Duchateau, N L; Verbruggen, A; Hendrickx, F; De Bièvre, P

    1986-04-01

    A procedure is described whereby rapid and accurate isotopic measurements can be performed on boron in boric acid and boron carbide after fusion of these compounds with calcium carbonate. It allows the determination of the isotopic composition of boron in boric acid and boron carbide and the direct assay of boron or the (10)B isotope in boron carbide by isotope-dilution mass spectrometry.

  15. Dosimetric model for intraperitoneal targeted liposomal radioimmunotherapy of ovarian cancer micrometastases

    Energy Technology Data Exchange (ETDEWEB)

    Syme, A M [Department of Physics, University of Alberta, 412 Avadh Bhatia Physics Laboratory, Edmonton, Alberta T6G 2J1 (Canada); McQuarrie, S A [Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, 3118 Dentistry/Pharmacy Centre, Edmonton, Alberta T6G 2N8 (Canada); Middleton, J W [Department of Physics, University of Ottawa, 150 Louis Pasteur, Ottawa, Ontario K1N 6N5 (Canada); Fallone, B G [Departments of Physics and Oncology, University of Alberta, 11560 University Avenue, Edmonton, Alberta T6G 1Z2 (Canada)

    2003-05-21

    A simple model has been developed to investigate the dosimetry of micrometastases in the peritoneal cavity during intraperitoneal targeted liposomal radioimmunotherapy. The model is applied to free-floating tumours with radii between 0.005 cm and 0.1 cm. Tumour dose is assumed to come from two sources: free liposomes in solution in the peritoneal cavity and liposomes bound to the surface of the micrometastases. It is assumed that liposomes do not penetrate beyond the surface of the tumours and that the total amount of surface antigen does not change over the course of treatment. Integrated tumour doses are expressed as a function of biological parameters that describe the rates at which liposomes bind to and unbind from the tumour surface, the rate at which liposomes escape from the peritoneal cavity and the tumour surface antigen density. Integrated doses are translated into time-dependent tumour control probabilities (TCPs). The results of the work are illustrated in the context of a therapy in which liposomes labelled with Re-188 are targeted at ovarian cancer cells that express the surface antigen CA-125. The time required to produce a TCP of 95% is used to investigate the importance of the various parameters. The relative contributions of surface-bound radioactivity and unbound radioactivity are used to assess the conditions required for a targeted approach to provide an improvement over a non-targeted approach during intraperitoneal radiation therapy. Using Re-188 as the radionuclide, the model suggests that, for microscopic tumours, the relative importance of the surface-bound radioactivity increases with tumour size. This is evidenced by the requirement for larger antigen densities on smaller tumours to affect an improvement in the time required to produce a TCP of 95%. This is because for the smallest tumours considered, the unbound radioactivity is often capable of exerting a tumouricidal effect before the targeting agent has time to accumulate

  16. A diaCEST MRI approach for monitoring liposomal accumulation in tumors.

    Science.gov (United States)

    Chan, Kannie W Y; Yu, Tao; Qiao, Yuan; Liu, Qiang; Yang, Ming; Patel, Himatkumar; Liu, Guanshu; Kinzler, Kenneth W; Vogelstein, Bert; Bulte, Jeff W M; van Zijl, Peter C M; Hanes, Justin; Zhou, Shibin; McMahon, Michael T

    2014-04-28

    Nanocarrier-based chemotherapy allows preferential delivery of therapeutics to tumors and has been found to improve the efficacy of cancer treatment. However, difficulties in tracking nanocarriers and evaluating their pharmacological fates in patients have limited judicious selection of patients to those who might most benefit from nanotherapeutics. To enable the monitoring of nanocarriers in vivo, we developed MRI-traceable diamagnetic Chemical Exchange Saturation Transfer (diaCEST) liposomes. The diaCEST liposomes were based on the clinical formulation of liposomal doxorubicin (i.e. DOXIL®) and were loaded with barbituric acid (BA), a small, organic, biocompatible diaCEST contrast agent. The optimized diaCEST liposomal formulation with a BA-to-lipid ratio of 25% exhibited 30% contrast enhancement at B1=4.7μT in vitro. The contrast was stable, with ~80% of the initial CEST signal sustained over 8h in vitro. We used the diaCEST liposomes to monitor the response to tumor necrosis factor-alpha (TNF-α), an agent in clinical trials that increases vascular permeability and uptake of nanocarriers into tumors. After systemic administration of diaCEST liposomes to mice bearing CT26 tumors, we found an average diaCEST contrast at the BA frequency (5ppm) of 0.4% at B1=4.7μT while if TNF-α was co-administered the contrast increased to 1.5%. This novel approach provides a non-radioactive, non-metallic, biocompatible, semi-quantitative, and clinically translatable approach to evaluate the tumor targeting of stealth liposomes in vivo, which may enable personalized nanomedicine.

  17. Encapsulation of trans-dehydrocrotonin in liposomes: an enhancement of the antitumor activity.

    Science.gov (United States)

    Lapenda, T L S; Morais, W A; Almeida, F J F; Ferraz, M S; Lira, M C B; Santos, N P S; Maciel, M A M; Santos-Magalhães, N S

    2013-03-01

    The aim of this study was the encapsulation of trans-dehydrocrotonin (t-DCTN) and its inclusion complexes with hydropropyl-beta-cyclodextrin (HP-beta-CD) in liposomes to improve t-DCTN antitumor activity. The in vitro kinetic profiles of t-DCTN-loaded liposomes (LD) and t-DCTN:HP-beta-CD-loaded liposomes (LC) were evaluated using the dialysis technique. The antitumor activity of LD and LC were investigated against Sarcoma 180 in Swiss mice. Histopathological and hematological analyses were carried out. The amounts of t-DCTN and t-DCTN:HP-beta-CD inclusion complex encapsulated in liposomes were equivalent to 1 mg of t-DCTN. The encapsulation efficiencies of LD and LC were 95.0 +/- 3.8% and 91.1 +/- 5.6%, respectively. In relation to kinetics, the drug release profiles of t-DCTN are in substantial agreement with the Fickian model. The treatment of animals with LD and LC produced tumor inhibitions of 79.4 +/- 9.6% and 63.5 +/- 5.5%, respectively. The liposomal encapsulation of t-DCTN by entrapment in the phospholipid bilayer increased at twice the antitumor activity. Moreover, the liposomal formulations reduced the hepatotoxicity effect of the drug and no significant hematological toxicity was observed in the treated animals. However, the counting of platelets was slightly decreased. Thus, the results show that the development of liposomal formulations containing t-DCTN or t-DCTN:HP-beta-CD is an important advance for enabling this drug to be use in therapy.

  18. Dual drug delivery using 'smart' liposomes for triggered release of anticancer agents

    Energy Technology Data Exchange (ETDEWEB)

    Jain, Ankit; Gulbake, Arvind; Jain, Ashish; Shilpi, Satish; Hurkat, Pooja; Jain, Sanjay K., E-mail: drskjainin@yahoo.com [Dr. Hari Singh Gour Vishwavidyalaya, Pharmaceutics Research Projects Laboratory, Department of Pharmaceutical Sciences (India)

    2013-07-15

    Ovarian cancer is one of the most fatal gynecologic cancers. In this debut study, dual approach using synergistically active combination of paclitaxel-topotecan (Pac-Top; 20:1, w/w) is investigated with utilization of characteristic features of tumor micro-environment and additionally overexpressed folate receptors (FR-{alpha}) to achieve targeting to tumor site. Various liposomes namely liposomes, PEGylated liposomes, and FR-targeted PEGylated liposomes with lipid compositions viz. DPPC:DMPG (85.5:9.5), DPPC:DMPG:mPEG{sub 2000}-DSPE (85.5:9.5:5), and DPPC:DMPG:mPEG{sub 2000}-DSPE:DSPE-PEG-folate (85.5:9.5:4.5:0.5), respectively, were developed using thin film casting method. These were nanometric in size around 200 nm. In vitro drug release study showed initial burst release followed by sustained release for more than 72 h at physiological milieu (37 {+-} 0.5 Degree-Sign C, pH 7.4) while burst release (i.e., more than 90 %) within 5 min at simulated tumor milieu (41 {+-} 1 Degree-Sign C, pH 4). SRB cytotoxicity assay in OVCAR-3 cell line revealed Pac-Top free (20:1, w/w) to be more toxic (GI{sub 50} = 6.5 {mu}g/ml) than positive control (Adriamycin, GI{sub 50} = 9.1 {mu}g/ml) and FR-targeted PEGylated liposomes GI{sub 50} (14.7 {mu}g/ml). Moreover, florescence microscopy showed the highest cell uptake of FR-targeted PEGylated liposomes so called 'smart liposomes' which has not only mediated effective targeting to FR-{alpha} but also triggered release of drugs upon hyperthermia.

  19. Wafer-Scale and Wrinkle-Free Epitaxial Growth of Single-Orientated Multilayer Hexagonal Boron Nitride on Sapphire.

    Science.gov (United States)

    Jang, A-Rang; Hong, Seokmo; Hyun, Chohee; Yoon, Seong In; Kim, Gwangwoo; Jeong, Hu Young; Shin, Tae Joo; Park, Sung O; Wong, Kester; Kwak, Sang Kyu; Park, Noejung; Yu, Kwangnam; Choi, Eunjip; Mishchenko, Artem; Withers, Freddie; Novoselov, Kostya S; Lim, Hyunseob; Shin, Hyeon Suk

    2016-05-11

    Large-scale growth of high-quality hexagonal boron nitride has been a challenge in two-dimensional-material-based electronics. Herein, we present wafer-scale and wrinkle-free epitaxial growth of multilayer hexagonal boron nitride on a sapphire substrate by using high-temperature and low-pressure chemical vapor deposition. Microscopic and spectroscopic investigations and theoretical calculations reveal that synthesized hexagonal boron nitride has a single rotational orientation with AA' stacking order. A facile method for transferring hexagonal boron nitride onto other target substrates was developed, which provides the opportunity for using hexagonal boron nitride as a substrate in practical electronic circuits. A graphene field effect transistor fabricated on our hexagonal boron nitride sheets shows clear quantum oscillation and highly improved carrier mobility because the ultraflatness of the hexagonal boron nitride surface can reduce the substrate-induced degradation of the carrier mobility of two-dimensional materials.

  20. A new and effective approach to boron removal by using novel boron-specific fungi isolated from boron mining wastewater.

    Science.gov (United States)

    Taştan, Burcu Ertit; Çakir, Dilara Nur; Dönmez, Gönül

    2016-01-01

    Boron-resistant fungi were isolated from the wastewater of a boron mine in Turkey. Boron removal efficiencies of Penicillium crustosum and Rhodotorula mucilaginosa were detected in different media compositions. Minimal Salt Medium (MSM) and two different waste media containing molasses (WM-1) or whey + molasses (WM-2) were tested to make this process cost effective when scaled up. Both isolates achieved high boron removal yields at the highest boron concentrations tested in MSM and WM-1. The maximum boron removal yield by P. crustosum was 45.68% at 33.95 mg l(-1) initial boron concentration in MSM, and was 38.97% at 42.76 mg l(-1) boron for R. mucilaginosa, which seemed to offer an economically feasible method of removing boron from the effluents.

  1. PEGylated liposomal vancomycin: a glimmer of hope for improving treatment outcomes in MRSA pneumonia.

    Science.gov (United States)

    Pumerantz, Andrew S

    2012-12-01

    Methicillin-resistant Staphylococcus aureus (MRSA) plays a significant role in the pandemic of multidrug resistant bacterial infections and is a major cause of hospital-acquired pneumonia. MRSA pneumonia carries a high morbidity and mortality rate especially in elderly diabetics with chronic kidney disease. S. aureus is highly virulent and successful respiratory pathogen. Vancomycin and linezolid are the only two antimicrobial agents FDA-approved to treat MRSA pneumonia. Standard vancomycin dosing is associated with high clinical failure rates and higher dosages are associated with increased nephrotoxicity. Pharmacokinetic and pharmacodynamic limitations are major contributors to poor outcomes with vancomycin. New agents are needed to improve treatment outcomes with MRSA pneumonia. Recently released antimicrobials with in vitro activity are not FDA-approved for treating MRSA pneumonia. Other novel agents are being investigated though none are in late-stage development. Pharmaceutical industry perception of low returns on investment, a Sisyphean regulatory environment, and obstacles to patentability have contributed to declining interest in both the development of novel antibiotics and the improvement of existing generic formulations. Despite decades of investigation into liposomal encapsulation as a drug delivery system that would increase efficacy and decrease toxicity, only liposomal amphotericin B and doxorubicin are commercially available. In this article, the pharmacokinetics and biodistribution of a novel PEGylated liposomal vancomycin formulation along with passive targeting and the enhanced permeability and retention effect of liposomal drug delivery; the pathogenesis of MRSA pneumonia; and recent patents of novel anti-MRSA agents, including inhalational liposomal vancomycin, are reviewed.

  2. Dendritic Cells Stimulated by Cationic Liposomes.

    Science.gov (United States)

    Vitor, Micaela Tamara; Bergami-Santos, Patrícia Cruz; Cruz, Karen Steponavicius Piedade; Pinho, Mariana Pereira; Barbuto, José Alexandre Marzagão; De La Torre, Lucimara Gaziola

    2016-01-01

    Immunotherapy of cancer aims to harness the immune system to detect and destroy cancer cells. To induce an immune response against cancer, activated dendritic cells (DCs) must present tumor antigens to T lymphocytes of patients. However, cancer patients' DCs are frequently defective, therefore, they are prone to induce rather tolerance than immune responses. In this context, loading tumor antigens into DCs and, at the same time, activating these cells, is a tempting goal within the field. Thus, we investigated the effects of cationic liposomes on the DCs differentiation/maturation, evaluating their surface phenotype and ability to stimulate T lymphocytes proliferation in vitro. The cationic liposomes composed by egg phosphatidylcholine, 1,2-dioleoyl-3-trimethylammonium propane and 1,2-dioleoylphosphatidylethanolamine (50/25/25% molar) were prepared by the thin film method followed by extrusion (65 nm, polydispersity of 0.13) and by the dehydration-rehydration method (95% of the population 107 nm, polydispersity of 0.52). The phenotypic analysis of dendritic cells and the analysis of T lymphocyte proliferation were performed by flow cytometry and showed that both cationic liposomes were incorporated and activated dendritic cells. Extruded liposomes were better incorporated and induced higher CD86 expression for dendritic cells than dehydrated-rehydrated vesicles. Furthermore, dendritic cells which internalized extruded liposomes also provided stronger T lymphocyte stimulation. Thus, cationic liposomes with a smaller size and polydispersity seem to be better incorporated by dendritic cells. Hence, these cationic liposomes could be used as a potential tool in further cancer immunotherapy strategies and contribute to new strategies in immunotherapy.

  3. A Review on Composite Liposomal Technologies for Specialized Drug Delivery

    Directory of Open Access Journals (Sweden)

    Maluta S. Mufamadi

    2011-01-01

    Full Text Available The combination of liposomes with polymeric scaffolds could revolutionize the current state of drug delivery technology. Although liposomes have been extensively studied as a promising drug delivery model for bioactive compounds, there still remain major drawbacks for widespread pharmaceutical application. Two approaches for overcoming the factors related to the suboptimal efficacy of liposomes in drug delivery have been suggested. The first entails modifying the liposome surface with functional moieties, while the second involves integration of pre-encapsulated drug-loaded liposomes within depot polymeric scaffolds. This attempts to provide ingenious solutions to the limitations of conventional liposomes such as short plasma half-lives, toxicity, stability, and poor control of drug release over prolonged periods. This review delineates the key advances in composite technologies that merge the concepts of depot polymeric scaffolds with liposome technology to overcome the limitations of conventional liposomes for pharmaceutical applications.

  4. Determination of boron over a large dynamic range by prompt-gamma activation analysis

    Energy Technology Data Exchange (ETDEWEB)

    Harrison, R.K. [University of Texas at Austin, Nuclear Engineering Teaching Lab., Pickle Research Campus, R-9000 Austin, TX 78712 (United States); Landsberger, S. [University of Texas at Austin, Nuclear Engineering Teaching Lab., Pickle Research Campus, R-9000 Austin, TX 78712 (United States)], E-mail: s.landsberger@mail.utexas.edu

    2009-02-15

    An evaluation of the PGAA method for the determination of boron across a wide dynamic range of concentrations was performed for trace levels up to 5 wt.% boron. This range encompasses a transition from neutron transparency to significant self- shielding conditions. To account for self-shielding, several PGAA techniques were employed. First, a calibration curve was developed in which a set of boron standards was tested and the count rate to boron mass curve was determined. This set of boron measurements was compared with an internal standard self-shielding correction method and with a method for determining composition using PGAA peak ratios. The advantages and disadvantages of each method are analyzed. The boron concentrations of several laboratory-grade chemicals and standard reference materials were measured with each method and compared. The evaluation of the boron content of nanocrystalline transition metals prepared with a boron-containing reducing agent was also performed with each of the methods tested. Finally, the k{sub 0} method was used for non-destructive measurement of boron in catalyst materials for the characterization of new non-platinum fuel cell catalysts.

  5. Boron toxicity causes multiple effects on Malus domestica pollen tube growth

    Directory of Open Access Journals (Sweden)

    Kefeng eFang

    2016-02-01

    Full Text Available Boron is an essential micronutrient for plants. However, boron is also toxic to cells at high concentrations, although the mechanism of this stress is not known. This study aimed to evaluate the effect of boron stress on Malus domestica pollen tube growth and its possible regulatory pathway. Our results show that a high concentration of boron inhibited pollen germination and tube growth and led to the morphological abnormality of pollen tubes. Fluorescent labeling coupled with a scanning ion-selective electrode technique detected that boron stress could decrease [Ca2+]c and induce the disappearance of the [Ca2+]c gradient, which are critical for pollen tube polar growth. Actin filaments were therefore altered by boron stress. Immuno-localization and fluorescence labeling, together with Fourier-transform infrared analysis (FTIR, suggested that boron stress influenced the accumulation and distribution of callose, de-esterified pectins, esterified pectins and arabinogalactan proteins in pollen tubes. All of the above results provide new insights into the regulatory role of boron in pollen tube development. In summary, boron likely plays a structural and regulatory role in relation to [Ca2+]c, actin cytoskeleton and cell wall components and thus regulates Malus domestica pollen germination and tube polar growth.

  6. Functional characterization of Citrus macrophylla BOR1 as a boron transporter.

    Science.gov (United States)

    Cañon, Paola; Aquea, Felipe; Rodríguez-Hoces de la Guardia, Amparo; Arce-Johnson, Patricio

    2013-11-01

    Plants have evolved to develop an efficient system of boron uptake and transport using a range of efflux carriers named BOR proteins. In this work we isolated and characterized a boron transporter of citrus (Citrus macrophylla), which was named CmBOR1 for its high homology to AtBOR1. CmBOR1 has 4403 bp and 12 exons. Its coding region has 2145 bp and encodes for a protein of 714 amino acids. CmBOR1 possesses the molecular features of BORs such as an anion exchanger domain and the presence of 10 transmembrane domains. Functional analysis in yeast indicated that CmBOR1 has an efflux boron transporter activity, and transformants have increased tolerance to excess boron. CmBOR1 is expressed in leaves, stem and flowers and shows the greatest accumulation in roots. The transcript accumulation was significantly increased under boron deficiency conditions in shoots. In contrast, the accumulation of the transcript did not change in boron toxicity conditions. Finally, we observed that constitutive expression of CmBOR1 was able to increase tolerance to boron deficiency conditions in Arabidopsis thaliana, suggesting that CmBOR1 is a xylem loading boron transporter. Based on these results, it was determined that CmBOR1 encodes a boric acid/borate transporter involved in tolerance to boron deficiency in plants.

  7. Targeting of pegylated liposomal mitomycin-C prodrug to the folate receptor of cancer cells: Intracellular activation and enhanced cytotoxicity.

    Science.gov (United States)

    Patil, Yogita; Amitay, Yasmine; Ohana, Patricia; Shmeeda, Hilary; Gabizon, Alberto

    2016-03-10

    Mitomycin C (MMC) is a powerful anti-bacterial, anti-fungal and anti-tumor antibiotic, often active against multidrug resistant cells. Despite a broad spectrum of antitumor activity, MMC clinical use is relatively limited due to its fast clearance and dose-limiting toxicity. To exploit the potential antitumor activity of MMC and reduce its toxicity we have previously developed a formulation of pegylated liposomes with a lipophilic prodrug of MMC (PL-MLP), activated by endogenous reducing agents which are abundant in the tumor cell environment in the form of different thiols. PL-MLP has minimal in vitro cytotoxicity unless reducing agents are added to the cell culture to activate the prodrug. In the present study, we hypothesized that targeting PL-MLP via folate receptors will facilitate intracellular activation of prodrug and enhance cytotoxic activity without added reducing agents. We grafted a lipophilic folate conjugate (folate-PEG(5000)-DSPE) to formulate folate targeted liposomes (FT-PL-MLP) and examined in vitro cell uptake and cytotoxic activity in cancer cell lines with high folate receptors (HiFR). 3H-cholesterol-hexadecyl ether (3H-Chol)-radiolabeled liposomes were prepared to study liposome-cell binding in parallel to cellular uptake of prodrug MLP. 3H-Chol and MLP cell uptake levels were 4-fold and 9-fold greater in KB HiFR cells when FT-PL-MLP is compared to non-targeted PL-MLP liposomes. The cytotoxic activity of FT-PL-MLP liposomes was significantly increased up to ~5-fold compared with PL-MLP liposomes in all tested HiFR expressing cell lines. The enhanced uptake and intracytoplasmic liposome delivery was confirmed by confocal fluorescence studies with Rhodamine-labeled liposomes. In vivo, no significant differences in pharmacokinetics and biodistribution were observed when PL-MLP was compared to FT-PL-MLP by the intravenous route. However, when liposomes were directly injected into the peritoneal cavity of mice with malignant ascites of J6456 Hi

  8. Improvement of labeling efficiency of glycoprotein-liposome conjugates with iodine-125 by using Bolton-Hunter Reagent and their distribution in mice

    Energy Technology Data Exchange (ETDEWEB)

    Kawakita, Yasunori; Kojima, Shuji [Science Univ. of Tokyo, Noda, Chiba (Japan). Research Institute for Biological Sciences; Yamazaki, Noboru

    2000-07-01

    We have developed a new type of glycoprotein-liposome conjugates and examined their potential utilities as drug-targeting carriers which exploit cellular functions of carbohydrate-binding proteins, i.e. animal lectins. An extremely low labeling efficiency, however, has been often a big problem in biodistribution study by using radiolabeled glycoprotein-liposome conjugates. In this study, improvement of the labeling efficiency was conducted by using Bolton-Hunter Reagent (BHR). First, tyrosyl groups were introduced into liposome membrane through amines of a constitutive phospholipid, dipalmitoylphosphatidlethanolamine (DPPE). Then, glycoprotein-tyrosyl group introduced liposomes were iodinated with {sup 125}I according to Chloramine-T methods. Labeling efficiency was markedly elevated in comparison with the BHR-untreated liposome conjugates. There was no significant changes in binding activity of BHR-treated glycoprotein-liposome conjugates with lectin. However, biodistribution of glycoprotein-tyrosyl group introduced liposomes in mice was significantly different from the mother conjugates. Thus, another suitable method for radioiodination of the glycoprotein-liposome conjugates should be developed. (author)

  9. Structural characterization of electrodeposited boron

    Indian Academy of Sciences (India)

    Ashish Jain; C Ghosh; T R Ravindran; S Anthonysamy; R Divakar; E Mohandas; G S Gupta

    2013-12-01

    Structural characterization of electrodeposited boron was carried out by using transmission electron microscopy and Raman spectroscopy. Electron diffraction and phase contrast imaging were carried out by using transmission electron microscopy. Phase identification was done based on the analysis of electron diffraction patterns and the power spectrum calculated from the lattice images from thin regions of the sample. Raman spectroscopic examination was carried out to study the nature of bonding and the allotropic form of boron obtained after electrodeposition. The results obtained from transmission electron microscopy showed the presence of nanocrystallites embedded in an amorphous mass of boron. Raman microscopic studies showed that amorphous boron could be converted to its crystalline form at high temperatures.

  10. Association with amino acids does not enhance efficacy of polymerized liposomes as a system for lung gene delivery

    OpenAIRE

    Elga eBernardo Bandeira De Melo; Miquéias eLopes-Pacheco; Nadia eChiaramoni; Débora eFerreira; Maria Julieta eFernandez-Ruocco; Maria Jimena ePrieto; Tatiana eMaron-Gutierrez; Perrotta, Ramiro M.; Hugo C Castro-Faria-Neto; Patricia Rieken Macedo Rocco; Silvia del Valle Alonso; Marcelo Marcos Morales

    2016-01-01

    Development of improved drug and gene delivery systems directly into the lungs is highly desirable given the important burden of respiratory diseases. We aimed to evaluate the safety and efficacy of liposomes composed of photopolymerized lipids (1,2-bis-(tricosa-10,12-diynoyl)-sn-glycero-3-phosphocholine) associated with amino acids as vectors for gene delivery into the lungs of healthy animals. Lipopolymer vesicles, in particular, are more stable than other types of liposomes. In this study,...

  11. Use of liposomes as injectable-drug delivery systems.

    Science.gov (United States)

    Ostro, M J; Cullis, P R

    1989-08-01

    The formation of liposomes and their application as delivery systems for injectable drugs are described. Liposomes are microscopic vesicles composed of one or more lipid membranes surrounding discrete aqueous compartments. These vesicles can encapsulate water-soluble drugs in their aqueous spaces and lipid-soluble drugs within the membrane itself. Liposomes release their contents by interacting with cells in one of four ways: adsorption, endocytosis, lipid exchange, or fusion. Liposome-entrapped drugs are distributed within the body much differently than free drugs; when administered intravenously to healthy animals and humans, most of the injected vesicles accumulate in the liver, spleen, lungs, bone marrow, and lymph nodes. Liposomes also accumulate preferentially at the sites of inflammation and infection and in some solid tumors; however, the reason for this accumulation is not clear. Four major factors influence liposomes' in vivo behavior and biodistribution: (1) liposomes tend to leak if cholesterol is not included in the vesicle membrane, (2) small liposomes are cleared more slowly than large liposomes, (3) the half-life of a liposome increases as the lipid dose increases, and (4) charged liposomal systems are cleared more rapidly than uncharged systems. The most advanced application of liposome-based therapy is in the treatment of systemic fungal infections, especially with amphotericin B. Liposomes are also under investigation for treatment of neoplastic disorders. Liposomes' uses in cancer therapy include encapsulation of known antineoplastic agents such as doxorubicin and methotrexate, delivery of immune modulators such as N-acetylmuramyl-L-alanine-D-isoglutamine, and encapsulation of new chemical entities that are synthesized with lipophilic segments tailored for insertion into lipid bilayers. Liposomal formulations of injectable antimicrobial agents and antineoplastic agents already are undergoing clinical testing, and most probably will receive

  12. Amphiphilic vinyl polymers effectively prolong liposome circulation time in vivo.

    Science.gov (United States)

    Torchilin, V P; Shtilman, M I; Trubetskoy, V S; Whiteman, K; Milstein, A M

    1994-10-12

    Newly synthesized amphiphilic polyacrylamide and poly(vinyl pyrrolidone), single terminus-modified with long-chain fatty acyl groups, are able to incorporate into the liposomal membrane, and similar to poly(ethylene glycol) prolong liposome circulation in vivo and decrease liposome accumulation in the liver. Protective efficacy of modified polymers increases with the increase in the length of acyl moiety and decreases for higher molecular weight polymers. The data on amphiphilic polymer-modified liposome biodistribution are presented.

  13. Combustion of boron containing compositions

    Energy Technology Data Exchange (ETDEWEB)

    Frolov, Y.; Pivkina, A. [Institute of Chemical Physics, Russian Academy of Science, Moscow (Russian Federation)

    1996-12-31

    Boron is one of the most energetic components for explosives, propellants and for heterogeneous condensed systems in common. The combustion process of mixtures of boron with different oxidizers was studied. The burning rate, concentration combustion limits, the agglomeration and dispersion processes during reaction wave propagation were analysed in the respect of the percolation theory. The linear dependence of the burning rate on the contact surface value was demonstrated. The percolative model for the experimental results explanation is proposed. (authors) 5 refs.

  14. Boron diffusion in silicon devices

    Science.gov (United States)

    Rohatgi, Ajeet; Kim, Dong Seop; Nakayashiki, Kenta; Rounsaville, Brian

    2010-09-07

    Disclosed are various embodiments that include a process, an arrangement, and an apparatus for boron diffusion in a wafer. In one representative embodiment, a process is provided in which a boric oxide solution is applied to a surface of the wafer. Thereafter, the wafer is subjected to a fast heat ramp-up associated with a first heating cycle that results in a release of an amount of boron for diffusion into the wafer.

  15. Noninvasive and persistent transfollicular drug delivery system using a combination of liposomes and iontophoresis.

    Science.gov (United States)

    Kajimoto, Kazuaki; Yamamoto, Masahiko; Watanabe, Misuzu; Kigasawa, Kaoru; Kanamura, Kiyoshi; Harashima, Hideyoshi; Kogure, Kentaro

    2011-01-17

    Iontophoresis is a promising technique for enhancing transdermal administration of charged drugs. However, conventional iontophoresis is not sufficient for effective delivery of large, hydrophilic, or electrically neutral molecules. In this study, we utilized charged liposomes as carriers, focused on a transfollicular route for delivery of the liposomes, and optimized iontophoretic conditions and lipid composition for this method in both in vitro and in vivo conditions. As a result, we identified the optimum condition (lipid composition: DOTAP/EPC/Chol=2:2:1, current supply: 0.45mA/cm(2), duration: 1h) for effective iontophoretic delivery of aqueous solution, which cannot be transferred into the skin without charged liposomes. We also examined the pharmacological effects of iontophoresis of liposomes encapsulating insulin (INS-lipo) using a rat model of type I diabetes. Interestingly, iontophoresis of INS-lipo onto a diabetes rat skin resulted in a gradual decrease in blood glucose levels, with levels reaching 20% of initial values at 18h after administration. These lower blood glucose levels were maintained for up to 24h. Significant amount of insulin were also detected in plasma 18h after iontophoresis of INS-lipo. We succeeded in developing a non-invasive and persistent transfollicular drug delivery system that used a combination of liposomes and iontophoresis.

  16. Intranasal delivery of liposomal indole-3-carbinol improves its pulmonary bioavailability.

    Science.gov (United States)

    Song, Jung Min; Kirtane, Ameya R; Upadhyaya, Pramod; Qian, Xuemin; Balbo, Silvia; Teferi, Fitsum; Panyam, Jayanth; Kassie, Fekadu

    2014-12-30

    Indole-3-carbinol (I3C), a constituent of commonly consumed Brassica vegetables, has been shown to have anticancer effects in a variety of preclinical models of lung cancer. However, it has shown only limited efficacy in clinical trials, likely due to its poor oral bioavailability. Intranasal administration of I3C has the potential to enhance the pulmonary accumulation of the drug, thereby improving its availability at the target site of action. In this study, we developed a liposomal formulation of I3C and evaluated its lung delivery and chemopreventive potential in tobacco smoke carcinogen [4-(methylnitro-samino)-1-(3-pyridyl)-1-butanone (NNK)]-treated mice. Intranasal administration of I3C liposomes led to a ∼100-fold higher lung exposure of I3C than the oral route of administration. Further, intranasal delivery of liposomal I3C led to a significant reduction (37%; pLiposomal I3C also significantly increased (by 10-fold) the expression of CYP1A1, a cytochrome P450 enzyme known to increase the detoxification of chemical carcinogens by enhancing their metabolism. Overall, our findings demonstrate that intranasal administration of liposomal I3C has the potential to significantly improve the efficacy of I3C for lung cancer chemoprevention.

  17. Liposomes as a model for the study of high frequency dielectrophoresis.

    Science.gov (United States)

    Hadady, Hanieh; Montiel, Caroline; Wetta, Daniel; Geiger, Emil J

    2015-07-01

    Liposomes were used as a physical model to study the dielectrophoretic response of single-shelled particles at high frequencies. For a typical particle, the single-shelled theoretical model predicts a lower cross-over frequency that depends upon the dielectric properties of the shell and an upper crossover frequency that depends upon the dielectric properties of the interior. Dried liposomes were rehydrated in media with conductivity ranging from 100 to 2000 μS/cm. The high frequency dielectrophoresis response of the liposomes was observed in the range of 1-80 MHz at 30 volts peak-to-peak, and the upper cross-over frequency was recorded. The experimental results closely matched the theoretical expectations. In particular, the upper cross-over frequency ranged from 9 to 60 MHz and was found to depend linearly on the interior conductivity of the liposome. These results further confirm the single-shell model at high-frequencies. Moreover, they suggest liposomes may be a useful model particle for use during the development of dielectrophoresis-based devices.

  18. Controlled drug-release system based on pH-sensitive chloride-triggerable liposomes.

    Science.gov (United States)

    Wehunt, Mark P; Winschel, Christine A; Khan, Ali K; Guo, Tai L; Abdrakhmanova, Galya R; Sidorov, Vladimir

    2013-03-01

    New pH-sensitive lipids were synthesized and utilized in formulations of liposomes suitable for controlled drug release. These liposomes contain various amounts of NaCl in the internal aqueous compartments. The release of the drug model is triggered by an application of HCl cotransporter and exogenous physiologically relevant NaCl solution. HCl cotransporter allows an uptake of HCl by liposomes to the extent of their being proportional to the transmembrane Cl(-) gradient. Therefore, each set of liposomes undergoes internal acidification, which, ultimately, leads to the hydrolysis of the pH-sensitive lipids and content release at the desired time. The developed system releases the drug model in a stepwise fashion, with the release stages separated by periods of low activity. These liposomes were found to be insensitive to physiological concentrations of human serum albumin and to be nontoxic to cells at concentrations exceeding pharmacological relevance. These results render this new drug-release model potentially suitable for in vivo applications.

  19. A Novel Approach for Transdermal Drug Delivery as a Liposomes their Progress and Limitations: A Review

    Directory of Open Access Journals (Sweden)

    Ambarish Gautam

    2012-11-01

    Full Text Available The transdermal route of drug delivery has gained great interest of pharmaceutical research, as it circumvents number of problems associated with oral route of drug administration. The uniqueness of this type of drug carrier system lies in the fact that it can accommodate hydrophilic, lipophilic as well as amphiphilic drugs. These drugs find place in different places in the vesicle before they get delivered beneath the skin. Liposomes are micro particulate lipoidal vesicles which are under extensive investigation as drug carriers for improving the delivery of therapeutic agents. Due to new developments in liposome technology, several liposome based drug formulations are currently in clinical trial, and recently some of them have been approved for clinical use. Reformulation of drugs in liposomes has provided an opportunity to enhance the therapeutic indices of various agents mainly through alteration in their bio distribution. This review discusses the potential applications of liposomes in drug delivery with examples of formulations approved for clinical use, and the problems associated with further exploitation of this drug delivery system.

  20. Physical characterization and cellular uptake of propylene glycol liposomes in vitro.

    Science.gov (United States)

    Zhang, Lu; Lu, Cui-Tao; Li, Wen-Feng; Cheng, Jin-Guo; Tian, Xin-Qiao; Zhao, Ying-Zheng; Li, Xing; Lv, Hai-Feng; Li, Xiao-Kun

    2012-03-01

    In order to facilitate the intracellular delivery of therapeutic agents, a new type of liposomes-propylene glycol liposomes (PGL) were prepared, and their cell translocation capability in vitro was examined. PGL was composed of hydrogenated egg yolk lecithin, cholesterol, Tween 80 and propylene glycol. With curcumin as a model drug, characterization of loaded PGL were measured including surface morphology, particle size, elasticity, encapsulation efficiency of curcumin and physical stability. Using curcumin-loaded conventional liposomes as the control, the cell uptake capacity of loaded PGL was evaluated by detection the concentration of curcumin in cytoplasm. Compared with conventional liposomes, PGL exhibited such advantages as high encapsulation efficiency (92.74% ± 3.44%), small particle size (182.4 ± 89.2 nm), high deformability (Elasticity index = 48.6) and high stability both at normal temperature (about 25°C) and low temperature at 4°C. From cell experiment in vitro, PGL exhibited the highest uptake of curcumin compared with that of conventional liposomes and free curcumin solution. Little toxic effect on cellular viability was observed by methyl tetrazolium assay. In conclusion, PGL might be developed as a promising intracellular delivery carrier for therapeutic agents.

  1. Preparation and Characterization of Naringenin-Loaded Elastic Liposomes for Topical Application.

    Directory of Open Access Journals (Sweden)

    Ming-Jun Tsai

    Full Text Available Excessive production of radical oxygen species in skin is a contributor to a variety of skin pathologies. Naringenin is a potent antioxidant. The purpose of the present study was to develop elastic liposomes for naringenin topical application. Naringenin-loaded elastic liposomes containing different amounts of Tween 80 and cholesterol were prepared. The physicochemical properties including vesicle size, surface charge, encapsulation efficiency, and permeability capacity were determined to evaluate the effect of components. The stability of formulation and skin irritation caused by drug-loaded elastic liposomes were also evaluated for assessment of the clinical utility of elastic liposomes. Saturated aqueous solution of naringenin and naringenin dissolved in 10% Tween 80 solution (5 mg/mL were used as the control group. The result showed that in using elastic liposomes as carrier, the deposition amounts in the skin of naringenin were significantly increased about 7.3~11.8-fold and 1.2~1.9-fold respectively, when compared with the saturated aqueous solution and Tween 80 solution-treated groups. The level of drug was more than 98.89±3.90% after 3 months of storage at 4℃. In a skin irritation test, the result showed experimental formulation exhibit considerably less irritating than the positive control (paraformaldehyde-treated group, suggesting its potential therapeutic application.

  2. Liposome-hepatocyte interactions : The role of plasma proteins

    NARCIS (Netherlands)

    Yan, Xuedong

    2005-01-01

    Liposomes have proved to be a useful drug delivery system as evidenced by several liposomal products that have reached the market in recent years [1]. However, many obstacles, such as low efficiency and specificity in delivering macromolecules to target sites, need to be overcome before liposomal dr

  3. Acoustical Properties of Individual Liposome-Loaded Microbubbles

    NARCIS (Netherlands)

    Luan, Y.; Faez, T.; Gelderblom, E.C.; Skachkov, I.; Geers, B.; Lentacker, I.; Steen, van der T.; Versluis, M.; Jong, de N.

    2012-01-01

    A comparison between phospholipid-coated microbubbles with and without liposomes attached to the microbubble surface was performed using the ultra-high-speed imaging camera (Brandaris 128). We investigated 73 liposome-loaded microbubbles (loaded microbubbles) and 41 microbubbles without liposome loa

  4. A novel liposomal formulation of flavopiridol.

    Science.gov (United States)

    Yang, Xiaojuan; Zhao, Xiaobin; Phelps, Mitch A; Piao, Longzhu; Rozewski, Darlene M; Liu, Qing; Lee, L James; Marcucci, Guido; Grever, Michael R; Byrd, John C; Dalton, James T; Lee, Robert J

    2009-01-05

    Flavopiridol has shown promising activities in hematologic and solid tumor models, as well as in clinical trials in chronic lymphocytic leukemia patients. Flavopiridol has relatively low solubility and high plasma protein-binding. To address these issues and to provide an alternative strategy to achieve clinical efficacy, we encapsulated flavopiridol into a liposomal carrier and characterized its physicochemical and pharmacokinetic properties. The liposomes, comprising hydrogenated soy phosphatidylcholine (HSPC), cholesterol and poly (ethylene glycol) 2000-distearoyl phosphatidylethanolamine (PEG-DSPE), were prepared by polycarbonate membrane extrusion and then loaded with flavopiridol by a pH-gradient driven remote loading procedure. The liposomes had a mean diameter of 120.7 nm and a flavopiridol entrapment efficiency of 70.4%. Pharmacokinetic study in mice after i.v. bolus injection showed that the liposomal flavopiridol had an increased elimination phase half-life (T((1/2)beta), 339.7 min vs. 57.0 min), decreased clearance (CL, 0.012 L/min vs. 0.036 L/min), and increased area under the plasma concentration-time curve (AUC, 10.8 min micromol/L vs. 3.4 min micromol/L) compared to the free drug. This indicates a significant and potentially beneficial change in flavopiridol pharmacokinetics for the liposomal formulation. Further preclinical studies are warranted to define the toxicity and therapeutic efficacy of this novel formulation.

  5. Lactosamination of liposomes and hepatotropic targeting research

    Institute of Scientific and Technical Information of China (English)

    Yong Peng Chen; Lian Zhang; Qiao Sheng Lu; Xiao Rong Feng; Kang Xian Luo

    2000-01-01

    Site-specific delivery of therapeutic drugs to their target cells is a major scientific challenge for the pharmaceutical sciences. It offers a number of advantages over conventional drug administration. With drug targeting, high local concentrations of the drug can be achieved, thus circumventing many unwanted side effects. Various carriers have been suggested for the delivery of drugs, including liposomes[1 - 5] and (neo ) glycoproteins[6-8]. The asialoglycoprotein receptor (ASGP-R) has frequently been utilized for targeting drugs to the parenchymal liver cell[6- 12]. Liposomes have several advantageous characteristics as drug carrier, and particularly, ligandtacked liposomes achieve a highly effective targeting[13]. Hara et al reported that asialofetuin (AF)-tacked liposomes distributed to rat hepatocytes selectively in vivo[14], and ASGP-R mediated the uptake of AF-liposomes encapsulating IFN-γ by isolated rat hepatocytes in vitro[15]. Lactosaminated human serum albumin (L-HSA) is a neoglycoprotein taking number of galactose residue as terminal sugar[6].

  6. Treatment of Digital Ischemia with Liposomal Bupivacaine

    Directory of Open Access Journals (Sweden)

    José Raul Soberón

    2014-01-01

    Full Text Available Objective. This report describes a case in which the off-label use of liposomal bupivacaine (Exparel in a peripheral nerve block resulted in marked improvement of a patient’s vasoocclusive symptoms. The vasodilating and analgesic properties of liposomal bupivacaine in patients with ischemic symptoms are unknown, but our clinical experience suggests a role in the management of patients suffering from vasoocclusive disease. Case Report. A 45-year-old African American female was admitted to the hospital with severe digital ischemic pain. She was not a candidate for any vascular surgical or procedural interventions. Two continuous supraclavicular nerve blocks were placed with modest clinical improvement. These effects were also short-lived, with the benefits resolving after the discontinuation of the peripheral nerve blocks. She continued to report severe pain and was on multiple anticoagulant medications, so a decision was made to perform an axillary nerve block using liposomal bupivacaine (Exparel given the compressibility of the site as well as the superficial nature of the target structures. Conclusions. This case report describes the successful off-label usage of liposomal bupivacaine (Exparel in a patient with digital ischemia. Liposomal bupivacaine (Exparel is currently FDA approved only for wound infiltration use at this time.

  7. Liposome-Loaded Cell Backpacks.

    Science.gov (United States)

    Polak, Roberta; Lim, Rosanna M; Beppu, Marisa M; Pitombo, Ronaldo N M; Cohen, Robert E; Rubner, Michael F

    2015-12-30

    Cell backpacks, or micron-scale patches of a few hundred nanometers in thickness fabricated by layer-by-layer (LbL) assembly, are potentially useful vehicles for targeted drug delivery on the cellular level. In this work, echogenic liposomes (ELIPs) containing the anticancer drug doxorubicin (DOX) are embedded into backpacks through electrostatic interactions and LbL assembly. Poly(allylamine hydrochloride)/poly(acrylic acid) (PAH/PAA)n , and poly(diallyldimethylammonium chloride)/poly(styrene sulfonate) (PDAC/SPS)n film systems show the greatest ELIP incorporation of the films studied while maintaining the structural integrity of the vesicles. The use of ELIPs for drug encapsulation into backpacks facilitates up to three times greater DOX loading compared to backpacks without ELIPs. Cytotoxicity studies reveal that monocyte backpack conjugates remain viable even after 72 h, demonstrating promise as drug delivery vehicles. Because artificial vesicles can load many different types of drugs, ELIP containing backpacks offer a unique versatility for broadening the range of possible applications for cell backpacks.

  8. Positron Emission Tomography Based Elucidation of the Enhanced Permeability and Retention Effect in Dogs with Cancer Using Copper-64 Liposomes

    DEFF Research Database (Denmark)

    Hansen, Anders Elias; Petersen, Anncatrine Luisa; Henriksen, Jonas Rosager

    2015-01-01

    included carcinomas displayed high uptake levels of liposomes, whereas one of four sarcomas displayed signs of liposome retention. We conclude that nanocarrier-radiotracers could be important in identifying cancer patients that will benefit from nanocarrier-based therapeutics in clinical practice.......Since the first report of the enhanced permeability and retention (EPR) effect, the research in nanocarrier based antitumor drugs has been intense. The field has been devoted to treatment of cancer by exploiting EPR-based accumulation of nanocarriers in solid tumors, which for many years......-effect in large animals and humans with spontaneously developed cancer. In the present paper, we describe a novel loading method of copper-64 into PEGylated liposomes and use these liposomes to evaluate the EPR-effect in 11 canine cancer patients with spontaneous solid tumors by PET/CT imaging. We thereby provide...

  9. Positron Emission Tomography Based Elucidation of the Enhanced Permeability and Retention Effect in Dogs with Cancer Using Copper-64 Liposomes

    DEFF Research Database (Denmark)

    Hansen, Anders Elias; Petersen, Anncatrine Luisa; Henriksen, Jonas Rosager;

    2015-01-01

    -effect in large animals and humans with spontaneously developed cancer. In the present paper, we describe a novel loading method of copper-64 into PEGylated liposomes and use these liposomes to evaluate the EPR-effect in 11 canine cancer patients with spontaneous solid tumors by PET/CT imaging. We thereby provide......Since the first report of the enhanced permeability and retention (EPR) effect, the research in nanocarrier based antitumor drugs has been intense. The field has been devoted to treatment of cancer by exploiting EPR-based accumulation of nanocarriers in solid tumors, which for many years...... included carcinomas displayed high uptake levels of liposomes, whereas one of four sarcomas displayed signs of liposome retention. We conclude that nanocarrier-radiotracers could be important in identifying cancer patients that will benefit from nanocarrier-based therapeutics in clinical practice....

  10. Tumor growth suppression by gadolinium-neutron capture therapy using gadolinium-entrapped liposome as gadolinium delivery agent.

    Science.gov (United States)

    Dewi, Novriana; Yanagie, Hironobu; Zhu, Haito; Demachi, Kazuyuki; Shinohara, Atsuko; Yokoyama, Kazuhito; Sekino, Masaki; Sakurai, Yuriko; Morishita, Yasuyuki; Iyomoto, Naoko; Nagasaki, Takeshi; Horiguchi, Yukichi; Nagasaki, Yukio; Nakajima, Jun; Ono, Minoru; Kakimi, Kazuhiro; Takahashi, Hiroyuki

    2013-07-01

    Neutron capture therapy (NCT) is a promising non-invasive cancer therapy approach and some recent NCT research has focused on using compounds containing gadolinium as an alternative to currently used boron-10 considering several advantages that gadolinium offers compared to those of boron. In this study, we evaluated gadolinium-entrapped liposome compound as neutron capture therapy agent by in vivo experiment on colon-26 tumor-bearing mice. Gadolinium compound were injected intravenously via tail vein and allowed to accumulate into tumor site. Tumor samples were taken for quantitative analysis by ICP-MS at 2, 12, and 24 h after gadolinium compound injection. Highest gadolinium concentration was observed at about 2 h after gadolinium compound injection with an average of 40.3 μg/g of wet tumor tissue. We performed neutron irradiation at JRR-4 reactor facility of Japan Atomic Energy Research Institute in Tokaimura with average neutron fluence of 2×10¹² n/cm². The experimental results showed that the tumor growth suppression of gadolinium-injected irradiated group was revealed until about four times higher compared to the control group, and no significant weight loss were observed after treatment suggesting low systemic toxicity of this compound. The gadolinium-entrapped liposome will become one of the candidates for Gd delivery system on NCT.

  11. Photodynamic activity of the boronated chlorin e6 amide in artificial and cellular membranes.

    Science.gov (United States)

    Antonenko, Yuri N; Kotova, Elena A; Omarova, Elena O; Rokitskaya, Tatyana I; Ol'shevskaya, Valentina A; Kalinin, Valery N; Nikitina, Roza G; Osipchuk, Julia S; Kaplan, Mikhail A; Ramonova, Alla A; Moisenovich, Mikhail M; Agapov, Igor I; Kirpichnikov, Mikhail P

    2014-03-01

    Photodynamic tumor-destroying activity of the boronated chlorin e6 derivative BACE (chlorin e6 13(1)-N-{2-[N-(1-carba-closo-dodecaboran-1-yl)methyl]aminoethyl}amide-15(2), 17(3)-dimethyl ester), previously described in Moisenovich et al. (2010) PLoS ONE 5(9) e12717, was shown here to be enormously higher than that of unsubstituted chlorin e6, being supported by the data on much higher photocytotoxicity of BACE in M-1 sarcoma cell culture. To validate membrane damaging effect as the basis of the enhanced tumoricidal activity, BACE was compared with unsubstituted chlorin e6 in the potency to photosensitize dye leakage from liposomes, transbilayer lipid flip-flop, inactivation of gramicidin A ionic channels in planar lipid membranes and erythrocyte hemolysis. In all the models comprising artificial and cellular membranes, the photodynamic effect of BACE exceeded that of chlorin e6. BACE substantially differed from chlorin e6 in the affinity to liposomes and erythrocytes, as monitored by fluorescence spectroscopy, flow cytometry and centrifugation. The results support the key role of membrane binding in the photodynamic effect of the boronated chlorin e6 amide.

  12. Imaging-based analysis of liposome internalization to macrophage cells: Effects of liposome size and surface modification with PEG moiety.

    Science.gov (United States)

    Lee, Jae Sun; Hwang, Sang Youn; Lee, E K

    2015-12-01

    Liposome is one of the frequently used carriers for active targeting systems in vivo. Such parameters as its size, surface charge, and surface modifiers are known to influence the liposome uptake by macrophage cells. In this study, we investigated the effects of liposome size and polyethylene glycol (PEG) surface modifier on the liposomal internalization to murine macrophage (RAW-264.7), by using an imaging analysis technique. Three different sized liposomes (100, 200, and 400 nm in nominal diameter) labeled with rhodamine fluorescence were used. Liposome internalization appeared to reach a pseudo-steady plateau in about 5h incubation, and most of the internalized liposomes were seen to accumulate in the cytosol including cellular extensions. The maximum fluorescent density from the internalized liposomes was similar between 100 nm and 200 nm liposomes. However, that of the larger 400 nm liposome was approximately 1.7 times higher than the others, confirming the previous report that the larger the liposomes are the higher the degree of internalization is. When the outside of the 200 nm liposomes was modified with biocompatible anchor molecule (BAM) consisting of PEG (ca. 2kD molecular weight) moiety, the endocytosis was indeed reduced by about 2.1-fold, despite the increase of the hydrodynamic size due to BAM conjugation. This fluorescence-based cellular imaging analysis can be used to quantitatively monitor and optimize cellular internalization systems.

  13. Rational design of liposomal drug delivery systems, a review: Combined experimental and computational studies of lipid membranes, liposomes and their PEGylation.

    Science.gov (United States)

    Bunker, Alex; Magarkar, Aniket; Viitala, Tapani

    2016-10-01

    Combined experimental and computational studies of lipid membranes and liposomes, with the aim to attain mechanistic understanding, result in a synergy that makes possible the rational design of liposomal drug delivery system (LDS) based therapies. The LDS is the leading form of nanoscale drug delivery platform, an avenue in drug research, known as "nanomedicine", that holds the promise to transcend the current paradigm of drug development that has led to diminishing returns. Unfortunately this field of research has, so far, been far more successful in generating publications than new drug therapies. This partly results from the trial and error based methodologies used. We discuss experimental techniques capable of obtaining mechanistic insight into LDS structure and behavior. Insight obtained purely experimentally is, however, limited; computational modeling using molecular dynamics simulation can provide insight not otherwise available. We review computational research, that makes use of the multiscale modeling paradigm, simulating the phospholipid membrane with all atom resolution and the entire liposome with coarse grained models. We discuss in greater detail the computational modeling of liposome PEGylation. Overall, we wish to convey the power that lies in the combined use of experimental and computational methodologies; we hope to provide a roadmap for the rational design of LDS based therapies. Computational modeling is able to provide mechanistic insight that explains the context of experimental results and can also take the lead and inspire new directions for experimental research into LDS development. This article is part of a Special Issue entitled: Biosimulations edited by Ilpo Vattulainen and Tomasz Róg.

  14. Liposomes containing glycocholate as potential oral insulin delivery systems: preparation, in vitro characterization, and improved protection against enzymatic degradation

    Directory of Open Access Journals (Sweden)

    Niu M

    2011-06-01

    Full Text Available Mengmeng Niu1, Yi Lu1, Lars Hovgaard2, Wei Wu11School of Pharmacy, Fudan University, Shanghai, People's Republic of China; 2Oral Formulation Development, Novo Nordisk A/S, Maalov, DenmarkBackground: Oral delivery of insulin is challenging and must overcome the barriers of gastric and enzymatic degradation as well as low permeation across the intestinal epithelium. The present study aimed to develop a liposomal delivery system containing glycocholate as an enzyme inhibitor and permeation enhancer for oral insulin delivery.Methods: Liposomes containing sodium glycocholate were prepared by a reversed-phase evaporation method followed by homogenization. The particle size and entrapment efficiency of recombinant human insulin (rhINS-loaded sodium glycocholate liposomes can be easily adjusted by tuning the homogenization parameters, phospholipid:sodium glycocholate ratio, insulin:phospholipid ratio, water:ether volume ratio, interior water phase pH, and the hydration buffer pH.Results: The optimal formulation showed an insulin entrapment efficiency of 30% ± 2% and a particle size of 154 ± 18 nm. A conformational study by circular dichroism spectroscopy and a bioactivity study confirmed the preserved integrity of rhINS against preparative stress. Transmission electron micrographs revealed a nearly spherical and deformed structure with discernable lamella for sodium glycocholate liposomes. Sodium glycocholate liposomes showed better protection of insulin against enzymatic degradation by pepsin, trypsin, and a-chymotrypsin than liposomes containing the bile salt counterparts of sodium taurocholate and sodium deoxycholate.Conclusion: Sodium glycocholate liposomes showed promising in vitro characteristics and have the potential to be able to deliver insulin orally.Keywords: liposomes, glycocholate, insulin, enzymatic degradation, oral

  15. Immunogenicity and Efficacy of Liposome-encapsulated Influenza Split Vaccine in BALB/c Mice

    Institute of Scientific and Technical Information of China (English)

    QI Feng-chun; WANG Chun-yi; WANG Ya-jun; ZHANG Xue-mei; ZHANG Yan; SUI Bo; LI Xiao-bo; SHENG Jun

    2007-01-01

    The cellular immunity of current influenza split vaccine is relatively low. It is necessary to develop a novel vaccine to improve the cellular immunity. The authors of this study prepared liposome-encapsulated influenza split vaccine and tested it in BALB/c mice. The mice were immunized once with 4 μg of haemagglutinin of monovalent A/New Caledonia/20/99(H1N1) encapsulated with liposomes or the split virus vaccine only through intrastomach injection. In a comparative study, it was observed that the liposome-encapsulated vaccine elicited a higher neutralizing antibody response, more effectively stimulated spleen cell proliferation, increased cell subsets like CD4+ and CD4+/CD8+, and triggered IL-4 and IFN-γ production.

  16. Biotin-conjugated fusogenic liposomes for high-quality cell purification.

    Science.gov (United States)

    Hersch, Nils; Wolters, Benjamin; Ungvari, Zoltan; Gautam, Tripti; Deshpande, Dhruva; Merkel, Rudolf; Csiszar, Anna; Hoffmann, Bernd; Csiszár, Agnes

    2016-01-01

    Purification of defined cell populations from mixed primary cell sources is essential for many biomedical and biotechnological applications but often very difficult to accomplish due to missing specific surface markers. In this study, we developed a new approach for efficient cell population separation based on the specific membrane fusion characteristics of distinct cell types upon treatment with fusogenic liposomes. When such liposomes are conjugated with biotin, specific cell populations can be efficiently surface functionalized by biotin after liposomal treatment while other populations remain unlabeled. Due to the high affinity of biotin for avidin-like proteins, biotin functionalized cells are ideal targets for conjugation of e.g. avidin tagged magnetic beads, fluorophores or antibodies with bioanalytical relevance. Here, based on the differential biotinylation of distinct cell populations high quality separation of cardiac fibroblasts from myocytes, and cerebromicrovascular endothelial cells from fibroblasts was successfully established.

  17. Dynamical and structural properties of lipid membranes in relation to liposomal drug delivery systems

    DEFF Research Database (Denmark)

    Jørgensen, Kent; Høyrup, Lise Pernille Kristine; Pedersen, Tina B.

    2001-01-01

    The structural and dynamical properties of DPPC liposomes containing lipopolymers (PEG-lipids) and charged DPPS lipids have been,studied in relation to the lipid membrane interaction of enzymes and peptides. The results suggest that both the lipid membrane structure and dynamics and in particular...... the appearance of small-scale lipid structures might be of importance for the activity of membrane associated and liposome degrading enzymes as well as for the membrane interaction of acylated peptides. The combined experimental and simulation results are of relevance for a rational development of peptide loaded...

  18. Serious stomatitis and esophagitis: a peculiar mucous reaction induced by pegylated liposomal doxorubicin.

    Science.gov (United States)

    Ma, Han; Chen, Meilan; Liu, Junru; Li, Ying; Li, Juan

    2015-01-01

    Pegylated liposomal doxorubicin is an important antineoplastic agent with activity in a variety of solid tumors. It has a totally different profile of pharmacokinetics and toxicity compared with doxorubicin. It rarely causes side-effects like cardiotoxicity or hair loss, but frequently results in many kinds of mucocutaneous reactions, including palmar-plantar erythrodysesthesia, diffuse follicular rash, intertrigo-like eruption, new formation of melanotic macules, stomatitis and radiation recall dermatitis. We present a rare case of multiple myeloma who immediately developed serious stomatitis and esophatitis associated with minor palmar-plantar erythrodysesthesia after a single course of pegylated liposomal doxorubicin.

  19. Microfluidic-enabled liposomes elucidate size-dependent transdermal transport.

    Directory of Open Access Journals (Sweden)

    Renee R Hood

    Full Text Available Microfluidic synthesis of small and nearly-monodisperse liposomes is used to investigate the size-dependent passive transdermal transport of nanoscale lipid vesicles. While large liposomes with diameters above 105 nm are found to be excluded from deeper skin layers past the stratum corneum, the primary barrier to nanoparticle transport, liposomes with mean diameters between 31-41 nm exhibit significantly enhanced penetration. Furthermore, multicolor fluorescence imaging reveals that the smaller liposomes pass rapidly through the stratum corneum without vesicle rupture. These findings reveal that nanoscale liposomes with well-controlled size and minimal size variance are excellent vehicles for transdermal delivery of functional nanoparticle drugs.

  20. Recent Trends of Polymer Mediated Liposomal Gene Delivery System

    Directory of Open Access Journals (Sweden)

    Shyamal Kumar Kundu

    2014-01-01

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

  1. Subcellular boron and fluorine distributions with SIMS ion microscopy in BNCT and cancer research

    Energy Technology Data Exchange (ETDEWEB)

    Subhash Chandra

    2008-05-30

    The development of a secondary ion mass spectrometry (SIMS) based technique of Ion Microscopy in boron neutron capture therapy (BNCT) was the main goal of this project, so that one can study the subcellular location of boron-10 atoms and their partitioning between the normal and cancerous tissue. This information is fundamental for the screening of boronated drugs appropriate for neutron capture therapy of cancer. Our studies at Cornell concentrated mainly on studies of glioblastoma multiforme (GBM). The early years of the grant were dedicated to the development of cryogenic methods and correlative microscopic approaches so that a reliable subcellular analysis of boron-10 atoms can be made with SIMS. In later years SIMS was applied to animal models and human tissues of GBM for studying the efficacy of potential boronated agents in BNCT. Under this grant the SIMS program at Cornell attained a new level of excellence and collaborative SIMS studies were published with leading BNCT researchers in the U.S.

  2. Liposomes for Use in Gene Delivery

    Directory of Open Access Journals (Sweden)

    Daniel A. Balazs

    2011-01-01

    Full Text Available Liposomes have a wide array of uses that have been continuously expanded and improved upon since first being observed to self-assemble into vesicular structures. These arrangements can be found in many shapes and sizes depending on lipid composition. Liposomes are often used to deliver a molecular cargo such as DNA for therapeutic benefit. The lipids used to form such lipoplexes can be cationic, anionic, neutral, or a mixture thereof. Herein physical packing parameters and specific lipids used for gene delivery will be discussed, with lipids classified according to overall charge.

  3. Therapeutic gas delivery via microbubbles and liposomes.

    Science.gov (United States)

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

    2015-07-10

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

  4. Preparation of High Purity Amorphous Boron Powder

    Directory of Open Access Journals (Sweden)

    K.V. Tilekar

    2005-10-01

    Full Text Available Amorphous boron powder of high purity (92-94 % with a particle size of l-2 mm is preferred as a fuel for fuel-rich propellants for integrated rocket ramjets and for igniter formulations. Thispaper describes the studies on process optimisation of two processes, ie, oxidative roasting of boron (roasting boron in air and roasting boron with zinc in an inert medium for preparing high purity boron. Experimental studies reveal that roasting boron with zinc at optimised process conditions yields boron of purity more than 93 per cent, whereas oxidative roasting method yields boron of purity - 92 per cent. Oxidative roasting has comparative edge over the other processes owing to its ease of scale-up and simplicity

  5. Liposomes as signal amplification reagents for bioassays in microfluidic channels.

    Science.gov (United States)

    Locascio, Laurie E; Hong, Jennifer S; Gaitan, Michael

    2002-03-01

    Liposomes with encapsulated carboxyfluorescein were used in an affinity-based assay to provide signal amplification for small-volume fluorescence measurements. Microfluidic channels were fabricated by imprinting in a plastic substrate material, poly(ethylene terephthalate glycol) (PETG), using a silicon template imprinting tool. Streptavidin was linked to the surface through biotinylated-protein for effective immobilization with minimal nonspecific adsorption of the liposome reagent. Lipids derivatized with biotin were incorporated into the liposome membrane to make the liposomes reactive for affinity assays. Specific binding of the liposomes to microchannel walls, dependence of binding on incubation time, and nonspecific adsorption of the liposome reagent were evaluated. The results of a competitive assay employing liposomes in the microchannels are presented.

  6. Aerosolized liposomes with dipalmitoyl phosphatidylcholine enhance pulmonary insulin delivery.

    Science.gov (United States)

    Chono, Sumio; Fukuchi, Rie; Seki, Toshinobu; Morimoto, Kazuhiro

    2009-07-20

    The pulmonary insulin delivery characteristics of liposomes were examined. Aerosolized liposomes containing insulin were administered into rat lungs and the enhancing effect on insulin delivery was evaluated by changes of plasma glucose levels. Liposomes with dipalmitoyl phosphatidylcholine (DPPC) enhanced pulmonary insulin delivery in rats, however, liposomes with dilauroyl, dimyristoyl, distearoyl or dioleoyl phosphatidylcholine did not. Liposomes with DPPC also enhanced the in vitro permeation of FITC dextran (Mw 4400, FD-4) through the calu-3 cell monolayer by reducing the transepithelial electrical resistance and did not harm lung tissues in rats. These findings suggest that liposomes with DPPC enhance pulmonary insulin delivery by opening the epithelial cell space in the pulmonary mucosa not mucosal cell damage. Liposomes with DPPC could be useful as a pulmonary delivery system for peptide and protein drugs.

  7. Role of the charge, carbon chain length, and content of surfactant on the skin penetration of meloxicam-loaded liposomes

    Directory of Open Access Journals (Sweden)

    Duangjit S

    2014-04-01

    Full Text Available Sureewan Duangjit,1,2 Boonnada Pamornpathomkul,1 Praneet Opanasopit,1 Theerasak Rojanarata,1 Yasuko Obata,2 Kozo Takayama,2 Tanasait Ngawhirunpat11Faculty of Pharmacy, Silpakorn University, Nakhon Pathom, Thailand; 2Department of Pharmaceutics, Hoshi University, Shinagawa-ku, Tokyo, JapanAbstract: The objective of this study was to investigate the influence of surfactant charge, surfactant carbon chain length, and surfactant content on the physicochemical characteristics (ie, vesicle size, zeta potential, elasticity, and entrapment efficiency, morphology, stability, and in vitro skin permeability of meloxicam (MX-loaded liposome. Moreover, the mechanism for the liposome-enhanced skin permeation of MX was determined by Fourier transform infrared spectroscopy and differential scanning calorimetry. The model formulation used in this study was obtained using a response surface method incorporating multivariate spline interpolation (RSM-S. Liposome formulations with varying surfactant charge (anionic, neutral, and cationic, surfactant carbon chain length (C4, C12, and C16, and surfactant content (10%, 20%, and 29% were prepared. The formulation comprising 29% cationic surfactant with a C16 chain length was found to be the optimal liposome for the transdermal delivery of MX. The skin permeation flux of the optimal formulation was 2.69-fold higher than that of a conventional liposome formulation. Our study revealed that surfactants affected the physicochemical characteristics, stability, and skin permeability of MX-loaded liposomes. These findings provide important fundamental information for the development of liposomes as transdermal drug delivery systems.Keywords: optimal liposome, optimization, transdermal drug delivery, surfactant charge, surfactant carbon chain length, surfactant content

  8. All-trans retinoic acid stealth liposomes prevent the relapse of breast cancer arising from the cancer stem cells.

    Science.gov (United States)

    Li, Ruo-Jing; Ying, Xue; Zhang, Yan; Ju, Rui-Jun; Wang, Xiao-Xing; Yao, Hong-Juan; Men, Ying; Tian, Wei; Yu, Yang; Zhang, Liang; Huang, Ren-Jie; Lu, Wan-Liang

    2011-02-10

    The relapse of cancer is mostly due to the proliferation of cancer stem cells which could not be eliminated by a standard chemotherapy. A new kind of all-trans retinoic acid stealth liposomes was developed for preventing the relapse of breast cancer and for treating the cancer in combination with a cytotoxic agent, vinorelbine stealth liposomes. In vitro studies were performed on the human breast cancer MCF-7 and MDA-MB-231 cells. In vivo evaluations were performed on the newly established relapse model with breast cancer stem cells. Results showed that the particle size of all-trans retinoic acid stealth liposomes was approximately 80nm, and the encapsulation efficiency was >90%. Breast cancer stem cells were identified with the CD44(+)/CD24(-) phenotype and characterized with properties: resistant to cytotoxic agent, stronger capability of proliferation, and stronger capability of differentiation. Inhibitory effect of all-trans retinoic acid stealth liposomes was more potent in cancer stem cells than in cancer cells. The mechanisms were defined to be two aspects: arresting breast cancer stem cells at the G(0)/G(1) phase in mitosis, and inducing the differentiation of breast cancer stem cells. The cancer relapse model was successfully established by xenografting breast cancer stem cells into NOD/SCID mice, and the formation and growth of the xenografted tumors were significantly inhibited by all-trans retinoic acid stealth liposomes. The combination therapy of all-trans retinoic acid stealth liposomes with vinorelbine stealth liposomes produced the strongest inhibitory effect to the relapse tumor model. It could be concluded that all-trans retinoic acid stealth liposomes could be used for preventing the relapse of breast cancer by differentiating cancer stem cells and arresting the cell-cycle, and for treating breast cancer as a co-therapy, thus providing a novel strategy for treating breast cancer and preventing relapse derived from breast cancer stem cells.

  9. Disorder and defects are not intrinsic to boron carbide

    Science.gov (United States)

    Mondal, Swastik; Bykova, Elena; Dey, Somnath; Ali, Sk Imran; Dubrovinskaia, Natalia; Dubrovinsky, Leonid; Parakhonskiy, Gleb; van Smaalen, Sander

    2016-01-01

    A unique combination of useful properties in boron-carbide, such as extreme hardness, excellent fracture toughness, a low density, a high melting point, thermoelectricity, semi-conducting behavior, catalytic activity and a remarkably good chemical stability, makes it an ideal material for a wide range of technological applications. Explaining these properties in terms of chemical bonding has remained a major challenge in boron chemistry. Here we report the synthesis of fully ordered, stoichiometric boron-carbide B13C2 by high-pressure–high-temperature techniques. Our experimental electron-density study using high-resolution single-crystal synchrotron X-ray diffraction data conclusively demonstrates that disorder and defects are not intrinsic to boron carbide, contrary to what was hitherto supposed. A detailed analysis of the electron density distribution reveals charge transfer between structural units in B13C2 and a new type of electron-deficient bond with formally unpaired electrons on the C–B–C group in B13C2. Unprecedented bonding features contribute to the fundamental chemistry and materials science of boron compounds that is of great interest for understanding structure-property relationships and development of novel functional materials.

  10. Ab initio modelling of boron related defects in amorphous silicon

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, Tiago A.; Torres, Vitor J.B. [Department of Physics, University of Aveiro, Campus Santiago, 3810-193 Aveiro (Portugal)

    2012-10-15

    We have modeled boron related point defects in amorphous silicon, using an ab initio method, the Density functional theory-pseudopotential code Aimpro. The boron atoms were embedded in 64 atom amorphous silicon cubic supercells. The calculations were performed using boron defects in 15 different supercells. These supercells were developed using a modified Wooten-Winer-Weaire bond switching mechanism. In average, the properties of the 15 supercells agree with the observed radial and bond angle distributions, as well the electronic and vibrational density of states and Raman spectra. In amorphous silicon it has been very hard to find real self-interstitials, since for almost all the tested configurations, the amorphous lattice relaxes overall. We found that substitutional boron prefers to be 4-fold coordinated. We find also an intrinsic hole-trap in the non-doped amorphous lattice, which may explain the low efficiency of boron doping. The local vibrational modes are, in average, higher than the correspondent crystalline values (copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

  11. Disorder and defects are not intrinsic to boron carbide.

    Science.gov (United States)

    Mondal, Swastik; Bykova, Elena; Dey, Somnath; Ali, Sk Imran; Dubrovinskaia, Natalia; Dubrovinsky, Leonid; Parakhonskiy, Gleb; van Smaalen, Sander

    2016-01-18

    A unique combination of useful properties in boron-carbide, such as extreme hardness, excellent fracture toughness, a low density, a high melting point, thermoelectricity, semi-conducting behavior, catalytic activity and a remarkably good chemical stability, makes it an ideal material for a wide range of technological applications. Explaining these properties in terms of chemical bonding has remained a major challenge in boron chemistry. Here we report the synthesis of fully ordered, stoichiometric boron-carbide B13C2 by high-pressure-high-temperature techniques. Our experimental electron-density study using high-resolution single-crystal synchrotron X-ray diffraction data conclusively demonstrates that disorder and defects are not intrinsic to boron carbide, contrary to what was hitherto supposed. A detailed analysis of the electron density distribution reveals charge transfer between structural units in B13C2 and a new type of electron-deficient bond with formally unpaired electrons on the C-B-C group in B13C2. Unprecedented bonding features contribute to the fundamental chemistry and materials science of boron compounds that is of great interest for understanding structure-property relationships and development of novel functional materials.

  12. CTG-loaded liposomes as an approach for improving the intestinal absorption of asiaticoside in Centella Total Glucosides.

    Science.gov (United States)

    Wang, Jiayu; Ma, Changhua; Guo, Chengjie; Yuan, Ruijuan; Zhan, Xueyan

    2016-07-25

    Centella Total Glucosides (CTG),obtained from Centella asiatica (L.), have been shown to possess a multitude of pharmacological activities, however, oral administeration of CTG failed to fulfill their therapeutic potentials due to the low bioavailability. In this study, the author prepared the liposomes encapsulated CTG using the ethanol injection method in order to enhance their intestinal absorption. The average particle size and the polydispersityindex(PDI) of CTG-loaded liposome in a batch are 137.0nm and 0.283, and the CTG-loaded amounts in CTG-loaded liposomes were 0.177mgmL(-1) and the zeta potential of CTG-loaded lipsomes is -21.2mV. The TEM images of CTG-loaded lipsomes showed that CTG-loaded liposomes are round and maintain high structural integrity, and their DSC thermograms indicated that CTG might be incorporated into the aqueous phase of DPPC to become more stable. The everted rat gut sac model was used to study the absorption characteristic of CTG-loaded solution in rat intestines. The cumulative absorption amount (Q) and the cumulative absorption percentage (P%) of asiaticoside in the CTG-loaded liposome was significantly higher than that in CTG (Pasiaticoside in CTG-loaded liposomes were significantly higher than those in CTG (Pasiaticoside in the ileum of the rats by enhancing its transmembrane permeability. The above study will provide the experimental evidence and a reference for the development of the oral dosage forms of Centella total glucosides.

  13. Preparation and in vitro evaluation of liposomal chloroquine diphosphate loaded by a transmembrane pH-gradient method.

    Science.gov (United States)

    Qiu, Liyan; Jing, Na; Jin, Yi

    2008-09-01

    This study developed an active loading method for encapsulating chloroquine diphosphate (CQ) into liposomes. The effects of different formulation factors on the encapsulation efficiency (EE) and the size of CQ liposomes were investigated. These factors included the internal phase of liposomes, the external phase of liposomes, the ratio of drug to soybean phosphatidylcholine (drug/SPC), the ratio of cholesterol to soybean phosphatidylcholine (Chol/SPC), and the incubation temperature and time. The EE (93%) was obtained when using drug/SPC (1:50 mass ratio), SPC/Chol (1:5 mass ratio) at 0.10 M citrate-sodium citrate buffer (pH 3.6). As 5 mol% methoxypoly(ethylene glycol)(2,000) cholesteryl succinate (CHS-PEG(2000)) or distearoyl phosphatidylethanolamine-poly (ethylene glycol)(2,000) (DSPE-PEG(2000)) was added, the size of particle was reduced and the EE was improved. Freeze-drying with 5% trehalose as a cryoprotectant was carried out to achieve long-term stability. The drug release studies were performed in vitro simulating the desired application conditions, such as physiological fluids (pH 7.4), tumor tissues (pH 6.5) and endosomal compartments (pH 5.5). The release of CQ from the liposomes prepared via remote loading showed the significant pH-sensitivity and retention properties, which favored the application of liposomal CQ at tumor tissues and endosomal compartments.

  14. Superior performance of liposomes over enzymatic amplification in a high-throughput assay for myoglobin in human serum.

    Science.gov (United States)

    Edwards, Katie A; Meyers, Katherine J; Leonard, Barbara; Baeumner, Antje J

    2013-05-01

    Myoglobin is one of several cardiac markers which become elevated in the blood following an acute myocardial infarction and can aid in the diagnosis of a heart attack. Here, a sandwich immunoassay for myoglobin was developed, including a thorough optimization of fluorescent dye-encapsulating liposomes versus enzymatic amplification (alkaline phosphatase and horseradish peroxidase) at each step. The optimized microtiter plate-based assay was capable of detecting as low as 11.3 pg/mL myoglobin and was successfully applied for the quantification of myoglobin in human serum. In comparison to enzymatic approaches, the liposomes demonstrated lower limits of detection, significantly reduced limits of quantification, improved signal discrimination through substantial signal enhancement, and reduced assay time. Liposomes were stable and functional at ambient temperatures for over 400 days. Finally, ease of use was greater due to lack of reliance on additional reagents, non-time-based signal enhancement, and excellent photostability. Optimal conditions identified for enzymatic approaches can also be used for liposome amplification, which makes substitution of these liposomes into existing assays straightforward. Thus, the extensive studies carried out here suggest that liposomes may be incorporated into formats currently utilizing enzymatic enhanced fluorescence with a potential for increased performance on various levels.

  15. Study on Leakage of Sesame (Sesamum indicum L. and Coconut (Cocos nucifera L. Liposomes

    Directory of Open Access Journals (Sweden)

    Dwi Hudiyanti

    2015-03-01

    Full Text Available Leakage phenomena on sesame (Sesamum indicum L. and coconut (Cocos nucifera L. liposomes has been studied to evaluate their ability as drug delivery materials. Permeation of carboxyfluorescein through the liposomes with and without added cholesterol was examined. Sesame liposomes release carboxyfluorescein less than coconut liposomes in all circumstances. Sesame liposomes save about 50% of payload after 17 hours of storage while coconut liposomes only 10%. Addition of cholesterol has increase storage capability of all liposomes. The sesame-cholesterol and coconut-cholesterol liposomes save greater amount of payload compare to the original. Sesame liposomes have better potency as drug delivery systems.

  16. Molecular medicine: Synthesis and in-vivo detection of agents for use in boron neutron capture therapy. Final report, May 1, 1993--April 30, 1996

    Energy Technology Data Exchange (ETDEWEB)

    Kabalka, G.W.

    1997-08-01

    During the early stages of this project, the author developed the first whole-body boron MRI technique. They found that, for the first time, information concerning both the location and the quantity of boron present in living tissues could be obtained through the use of magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) respectively. However, it was also discovered that boron MRI was not without problems. Both naturally occurring isotopes of boron (boron-10 and boron-11) possess magnetic moments, making them amenable to MR detection. The author found that there are difficulties in obtaining boron MRI images which are a consequence of the inherently poor magnetic resonance characteristics of the boron nucleus. The magnetogyric ratios of both boron-10 and boron-11 are smaller than those of hydrogen, which makes boron much less sensitive to magnetic resonance detection. In addition, both isotopes of boron posses nuclear electric quadrupole moments which serve to shorten their magnetization relaxation times; this causes the MR signal to broaden and decay rapidly, often before the receiver coils can collect the MR information. The rapid rate of signal decay is enhanced in biological systems which leads to further signal loss and a decrease in the signal to noise ratio (SNR).

  17. Liposomal bupivacaine: an innovative nonopioid local analgesic for the management of postsurgical pain.

    Science.gov (United States)

    Candiotti, Keith

    2012-09-01

    Local anesthetics are a cornerstone of multimodal pain control strategies in the surgical setting as they have a long history of use and an established safety profile. Although effective, their duration of action is relatively short, which usually leads to the use of other agents, such as opioids, for effective postsurgical pain control in most patients. A medical need exists to extend the duration of analgesia with local anesthetics to help reduce the reliance on opioids in the postsurgical setting. Liposomal bupivacaine uses a product delivery platform to release bupivacaine slowly over 96 hours after infiltration at the surgical site. Liposomal bupivacaine was compared with placebo in two pivotal, multicenter, randomized, double-blind, parallel-group trials in 189 adults undergoing soft-tissue surgery (hemorrhoidectomy) and 193 adults undergoing orthopedic surgery (bunionectomy). Among patients undergoing hemorrhoidectomy, liposomal bupivacaine significantly reduced cumulative pain scores for up to 72 hours (primary end point) as measured by the area under the curve of pain scores on the numeric rating scale (pliposomal bupivacaine significantly reduced total consumption of rescue opioids (p=0.0077) and cumulative pain scores as measured by the area under the curve of pain scores on the numeric rating scale (p=0.0005) during the first 24 postsurgical hours (primary end point) relative to placebo. Furthermore, liposomal bupivacaine also significantly delayed the time to first use of opioid rescue (pliposomal bupivacaine were nausea, vomiting, and constipation. No adverse effects on the QTc interval or cardiac safety signal have been detected in the clinical trial development program (823 patients) when liposomal bupivacaine was infiltrated into the surgical site. The beneficial effects of liposomal bupivacaine on postsurgical pain management and opioid use, significantly reducing both, are likely to translate into improved clinical and economic outcomes.

  18. Drug-in-cyclodextrin-in-liposomes: A novel drug delivery system for flurbiprofen.

    Science.gov (United States)

    Zhang, Lina; Zhang, Qi; Wang, Xin; Zhang, Wenji; Lin, Congcong; Chen, Fen; Yang, Xinggang; Pan, Weisan

    2015-08-15

    A novel delivery system based on drug-cyclodextrin (CD) complexation and liposomes has been developed to improve therapeutic effect. Three different means, i.e., co-evaporation (COE), co-ground (GR) and co-lyophilization (COL) and three different CDs (β-CD, HP-β-CD and SBE-β-CD) were contrasted to investigate the characteristics of the end products. FP/FP-CD loaded liposomes were obtained by thin layer evaporation technique. Size, zeta potential and encapsulation efficiency were investigated by light scattering analysis and minicolumn centrifugation. Differential scanning calorimetry (DSC) and transmission electron microscopy (TEM) showed the amorphous form of complexes and spherical morphology of FP-HP-β-CD COE loaded liposomes. The pH 7.4 phosphate buffer solution (PBS) was selected as the medium for the in vitro release. Wistar rats were put into use to study the pharmacokinetic behavior in vivo. FP-HP-β-CD COE loaded liposomes showed the better physicochemical characters that followed the average particle size, polydispersity index, zeta potential and mean encapsulation efficiency 158±10 nm, 0.19±0.1, -12.4±0.1 mW and 56.1±0.5%, separately. The relative bioavailability of FP-HP-β-CD COE loaded liposomes was 420%, 201% and 402% compared with FP solution, FP-HP-β-CD and FP-liposomes, respectively. In conclusion, the novel delivery system improved the relative bioavailability of FP significantly and provided a perspective way for delivery of insoluble drugs.

  19. AmBisome: liposomal formulation, structure, mechanism of action and pre-clinical experience.

    Science.gov (United States)

    Adler-Moore, Jill; Proffitt, Richard T

    2002-02-01

    Amphotericin B is the treatment of choice for life-threatening systemic fungal infections such as candidosis and aspergillosis. To improve this drug's efficacy and reduce its acute and chronic toxicities, several lipid formulations of the drug have been developed, including AmBisome, a liposomal formulation of amphotericin B. The liposome is composed of high transition temperature phospholipids and cholesterol, designed to incorporate amphotericin B securely into the liposomal bilayer. AmBisome can bind to fungal cell walls, where the liposome is disrupted. The amphotericin B, after being released from the liposomes, is thought to transfer through the cell wall and bind to ergosterol in the fungal cell membrane. This mechanism of action of AmBisome results in its potent in vitro fungicidal activity while the integrity of the liposome is maintained in the presence of mammalian cells, for which it has minimal toxicity. In animal models, AmBisome is effective in treating both intracellular (leishmaniasis and histoplasmosis) and extracellular (candidosis and aspergillosis) systemic infections. Because of its low toxicity at the organ level, intravenous AmBisome can be safely delivered at markedly high doses of amphotericin B (1-30 mg/kg) for the treatment of systemic fungal infections. AmBisome has a circulating half-life of 5-24 h in animals, and in animal models appears to localize at sites of infection in the brain (cryptococcosis, aspergillosis, coccidioidomycosis), lungs (blastomycosis, paracoccidioidomycosis, aspergillosis) and kidneys (candidosis), delivering amphotericin B that remains bioavailable in tissues for several weeks following treatment.

  20. Prospects of liposomes using for creating of new forms of the medicinal and preventive preparations

    Directory of Open Access Journals (Sweden)

    M. A. Kisjakova

    2010-07-01

    Full Text Available Information on the structure, physical and chemical characteristics of the phospholipid vesicles (liposomes – the effective natural drug delivery system is presented. Types of liposomes, procedures of its productions, penetration mechanisms into cells and functional features of liposomal drugs are described. Data on production of liposomes with lactobacilli acellular homogenates and the methods of the liposomes structure control asre demonstrated.

  1. Reversal of the multidrug resistance by drug combination using multifunctional liposomes

    Science.gov (United States)

    Patel, Niravkumar R.

    One of the major obstacles to the success of cancer chemotherapy is the multi-drug resistance (MDR) that results due mainly to the over-expression of drug efflux transporter pumps such as P-glycoprotein (P-gp). Highly efficacious third generation P-gp inhibitors, like tariquidar, have shown promising results against MDR. However, P-gp is also expressed in normal tissues like the blood-brain barrier, gastrointestinal tract, liver and kidney. It is therefore important to limit the exposure of P-gp inhibitors to normal tissues and increase their co-localization with anticancer agents in tumor tissues to maximize the efficacy of a P-gp inhibitor. To minimize non-specific binding and increase its delivery to tumor tissues, liposomes, self-assembling phospholipid vesicles, were chosen as a drug delivery vehicle. The liposome has been identified as a system capable of carrying molecules with diverse physicochemical properties. It can also alter the pharmacokinetic profile of loaded molecules which is a concern with both tariquidar and paclitaxel. Liposomes can easily be surface-modified rendering them cell-specific as well as organelle-specific. The main objective of present study was to develop an efficient liposomal delivery system which would deliver therapeutic molecules of interest to tumor tissues and avoid interaction with normal tissues. In this study, the co-delivery of tariquidar and paclitaxel into tumor cells to reverse the MDR using long-circulating cationic liposomes was investigated. SKOV-3TR, the resistant variant of SKOV-3 and MCF-7/ADR, the resistant variant of MCF-7 were used as model cell lines. Uniform liposomal formulations were generated with high incorporation efficiency and no apparent decrease in tariquidar potency towards P-gp. Tariquidar- and paclitaxel- co-loaded long-circulating liposomes showed significant re-sensitization of SKOV-3TR and MCF-7/ADR for paclitaxel in vitro. Further modification of these liposomes with antitumor 2C5 resulted

  2. A boron-boron coupling reaction between two ethyl cation analogues.

    Science.gov (United States)

    Litters, Sebastian; Kaifer, Elisabeth; Enders, Markus; Himmel, Hans-Jörg

    2013-12-01

    The design of larger architectures from smaller molecular building blocks by element-element coupling reactions is one of the key concerns of synthetic chemistry, so a number of strategies were developed for this bottom-up approach. A general scheme is the coupling of two elements with opposing polarity or that of two radicals. Here, we show that a B-B coupling reaction is possible between two boron analogues of the ethyl cation, resulting in the formation of an unprecedented dicationic tetraborane. The bonding properties in the rhomboid B₄ core of the product can be described as two B-B units connected by three-centre, two-electron bonds, sharing the short diagonal. Our discovery might lead the way to the long sought-after boron chain polymers with a structure similar to the silicon chains in β-SiB₃. Moreover, the reaction is a prime textbook example of the influence of multiple-centre bonding on reactivity.

  3. Structures, stability, mechanical and electronic properties of a-boron and its twined brother a*-boron

    OpenAIRE

    He, Chaoyu; Zhong, Jianxin

    2013-01-01

    The structures, stability, mechanical and electronic properties of a-boron and its twined brother a*-boron have been studied by first-principles calculations. Both a-boron and a*-boron consist of equivalent icosahedra B12 clusters in different connecting configurations of "3S-6D-3S" and "2S-6D-4S", respectively. The total energy calculations show that a*-boron is less stable than a-boron but more favorable than beta-boron and Gamma-boron at zero pressure. Both a-boron and a*-boron are confirm...

  4. Extractive fixed-site polymer sorbent for selective boron removal from natural water.

    Science.gov (United States)

    Thakur, Neha; Kumar, Sanjukta A; Shinde, Rakesh N; Pandey, Ashok K; Kumar, Sangita D; Reddy, A V R

    2013-09-15

    Water contamination by boron is a widespread environmental problem. The World Health Organization (WHO) recommends maximum boron concentration of 2.4 mg L(-1) for drinking water. The paper presents a simple method for preparation of functionalized sheet sorbent for selective extraction of boron from natural water. The pores of commercially available poly(propylene) membrane were functionalized by room temperature in situ crosslinking of poly(vinylbenzyl chloride) with a cyclic diamine piperazine. The precursor membranes were chemically modified with N-methyl D-glucamine which is selective for boron. Characterization of membrane was carried out using scanning electron microscopy (SEM) and attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) techniques. The functionalized membrane has been characterized in terms of parameters that influence the sorption of boron from aqueous streams like pH, uptake capacity, contact time, effects of competing ions and reusability. The maximum boron sorption capacity determined experimentally was 28 mg g(-1). The studies showed that trace concentrations of boron were quantitatively removed from water at neutral pH. The developed fixed site polymer sorbent exhibited high sorption capacity and fast kinetics as compared to various sorbents reported in literature. It was successfully applied for the removal of boron from ground water and seawater samples in presence of high concentration of interfering ions.

  5. Chitosan coated vancomycin hydrochloride liposomes: Characterizations and evaluation.

    Science.gov (United States)

    Yang, Zhenlei; Liu, Junli; Gao, Jinhua; Chen, Shilei; Huang, Guihua

    2015-11-10

    The present work evaluated the feasibility of chitosan coated liposomes (c-Lips) for the intravenous delivery of vancomycin hydrochloride (VANH), a water-soluble antibiotic for the treatment of gram-positive bacterial infections like osteomyelitis, arthritis, endocarditis, pneumonia, etc. The objective of this research was to develop a suitable drug delivery system in vivo which could improve therapeutic efficacy and decrease side effects especially nephrotoxicity. Firstly, the vancomycin hydrochloride liposomes (VANH-Lips) were prepared by modified reverse phase evaporation method, then the chitosan wrapped vancomycin hydrochloride liposomes (c-VANH-Lips) nanosuspension was formulated by the method of electrostatic deposition. Based on the optimized results of single-factor screening experiment, the c-VANH-Lips were found to be relatively uniform in size (220.40 ± 3.56 nm) with a narrow polydispersity index (PI) (0.21 ± 0.03) and a positive zeta potential (25.7 ± 1.12 mV). The average drug entrapment efficiency (EE) and drug loading (DL) were 32.65 ± 0.59% and 2.18 ± 0.04%, respectively. The in vitro release profile of c-VANH-Lips possessed a sustained release Characterization and the release behavior was in accordance with the Weibull equation. Hemolysis experiments showed that its intravenous injection had preliminary safety. In vivo, after intravenous injection to mice, c-VANH-Lips showed a longer retention time and higher AUC values compared with the VANH injection (VANH-Inj) and VANH-Lips. In addition, biodistribution results clearly demonstrated that c-VANH-Lips preferentially decreased the drug distribution in kidney of mice after intravenous injection. These results revealed that injectable c-VANH-Lips may serve as a promising carrier for VANH to increase therapeutic efficacy on gram-positive bacterial infections and reduce nephrotoxicity, which provides significantly clinical value for long-term use of VANH.

  6. Vaccination of mice with liposome-entrapped adult antigens of Nippostrongylus brasiliensis.

    Science.gov (United States)

    Rhalem, A; Bourdieu, C; Luffau, G; Pery, P

    1988-01-01

    An immunization procedure was developed to induce protection of mice against the gastrointestinal helminth Nippostrongylus brasiliensis. Mice immunized by the oral route with antigens which were released by adult worms during their in vitro survival in a detergent-containing medium and which were entrapped in liposomes were protected against a challenge infection.

  7. Polydiacetylene-Based Liposomes: An "Optical Tongue" for Bacteria Detection and Identification

    Science.gov (United States)

    West, Matthew R.; Hanks, Timothy W.; Watson, Rhett T.

    2009-01-01

    Food- and water-borne bacteria are a major health concern worldwide. Current detection methods are time-consuming and require sophisticated equipment that is not always readily available. However, new techniques based on nanotechnology are under development that will result in a new generation of sensors. In this experiment, liposomes are…

  8. Analytical and experimental research into boron dilution events

    Energy Technology Data Exchange (ETDEWEB)

    Teschendorff, V. [Gesellschaft fuer Anlagen- und Reaktorsicherheit (GRS) mbH, Garching (Germany); Umminger, K. [Framatome ANP GmbH, Erlengen (Germany); Weiss, F.P. [Forschungszentrum Rossendorf e.V. (FZR) (Germany). Inst. fuer Sicherheitsforschung

    2001-07-01

    Research activities are being performed in Germany with the aim to improve and validate the methods for predicting boron dilution events. Integral experiments in the PKL test facility investigate the thermal-hydraulic system behaviour in a wide range of conditions. The latest test program comprises small break LOCA scenarios with boron dilution. For these tests, boric acid in the coolant is used together with an advanced instrumentation that can measure boron concentration during the transient. Mixing processes in the downcomer and lower plenum under the influence of various loop operating conditions are studied in the transparent 1:5 ROCOM four-loop test facility equipped with advanced wire mesh sensors to follow the transient concentration patterns. Analytical R and D activities include further model development and validation in the thermal-hydraulic system code ATHLET as well as assessment calculations for detailed three-dimensional mixing in the reactor pressure vessel with CFD-codes. (authors)

  9. Liposomal drug delivery: recent patents and emerging opportunities.

    Science.gov (United States)

    Webb, Murray S; Rebstein, Patrick; Lamson, Wendy; Bally, Marcel B

    2007-01-01

    It is challenging to develop innovative, as well as commercially viable, lipid-based drug delivery systems for the treatment of cancer because of the breadth of existing intellectual property that limits freedom-to-operate. For example, novel compositions can be described in which a new chemical entity is associated with a lipid based carrier, but if the loading method or components of the lipid compositions are proprietary then the ability to develop novel compositions will require access to the appropriate intellectual property. We believe it is useful to present a review of the patent literature describing novel liposomal drug delivery systems given by parenteral administration to humans for the treatment of serious medical conditions such as cancer. This review is intended to: (i) identify and describe novel approaches that have recently been protected by US or international patents and patent applications, and; (ii) identify founding technology in the field which is recently off-patent, thus presenting emerging opportunities for the development of new therapeutic options for patients. Issued patents, and selected patent applications, having publication dates in 2005 or 2006 were retrieved from searches of the US, European, German, Japanese, INPADOC and WIPO PCT databases. Liposomal delivery systems patented for systemic administration in the treatment of human medical conditions were reviewed in detail.

  10. Boron doping a semiconductor particle

    Science.gov (United States)

    Stevens, Gary Don; Reynolds, Jeffrey Scott; Brown, Louanne Kay

    1998-06-09

    A method (10,30) of boron doping a semiconductor particle using boric acid to obtain a p-type doped particle. Either silicon spheres or silicon powder is mixed with a diluted solution of boric acid having a predetermined concentration. The spheres are dried (16), with the boron film then being driven (18) into the sphere. A melt procedure mixes the driven boron uniformly throughout the sphere. In the case of silicon powder, the powder is metered out (38) into piles and melted/fused (40) with an optical furnace. Both processes obtain a p-type doped silicon sphere with desired resistivity. Boric acid is not a restricted chemical, is inexpensive, and does not pose any special shipping, handling, or disposal requirements.

  11. Influence of the Encapsulation Efficiency and Size of Liposome on the Oral Bioavailability of Griseofulvin-Loaded Liposomes

    Science.gov (United States)

    Ong, Sandy Gim Ming; Ming, Long Chiau; Lee, Kah Seng; Yuen, Kah Hay

    2016-01-01

    The objective of the present study was to investigate the influence of the encapsulation efficiency and size of liposome on the oral bioavailability of griseofulvin-loaded liposomes. Griseofulvin-loaded liposomes with desired characteristics were prepared from pro-liposome using various techniques. To study the effect of encapsulation efficiency, three preparations of griseofulvin, namely, griseofulvin aqueous suspension and two griseofulvin-loaded liposomes with different amounts of griseofulvin encapsulated [i.e., F1 (32%) and F2(98%)], were administered to rats. On the other hand, to study the effect of liposome size, the rats were given three different griseofulvin-loaded liposomes of various sizes, generated via different mechanical dispersion techniques [i.e., FTS (142 nm), MS (357 nm) and NS (813 nm)], but with essentially similar encapsulation efficiencies (about 93%). Results indicated that the extent of bioavailability of griseofulvin was improved 1.7–2.0 times when given in the form of liposomes (F1) compared to griseofulvin suspension. Besides that, there was an approximately two-fold enhancement of the extent of bioavailability following administration of griseofulvin-loaded liposomes with higher encapsulation efficiency (F2), compared to those of F1. Also, the results showed that the extent of bioavailability of liposomal formulations with smaller sizes were higher by approximately three times compared to liposomal formulation of a larger size. Nevertheless, a further size reduction of griseofulvin-loaded liposome (≤400 nm) did not promote the uptake or bioavailability of griseofulvin. In conclusion, high drug encapsulation efficiency and small liposome size could enhance the oral bioavailability of griseofulvin-loaded liposomes and therefore these two parameters deserve careful consideration during formulation. PMID:27571096

  12. Influence of the Encapsulation Efficiency and Size of Liposome on the Oral Bioavailability of Griseofulvin-Loaded Liposomes

    Directory of Open Access Journals (Sweden)

    Sandy Gim Ming Ong

    2016-08-01

    Full Text Available The objective of the present study was to investigate the influence of the encapsulation efficiency and size of liposome on the oral bioavailability of griseofulvin-loaded liposomes. Griseofulvin-loaded liposomes with desired characteristics were prepared from pro-liposome using various techniques. To study the effect of encapsulation efficiency, three preparations of griseofulvin, namely, griseofulvin aqueous suspension and two griseofulvin-loaded liposomes with different amounts of griseofulvin encapsulated [i.e., F1 (32% and F2(98%], were administered to rats. On the other hand, to study the effect of liposome size, the rats were given three different griseofulvin-loaded liposomes of various sizes, generated via different mechanical dispersion techniques [i.e., FTS (142 nm, MS (357 nm and NS (813 nm], but with essentially similar encapsulation efficiencies (about 93%. Results indicated that the extent of bioavailability of griseofulvin was improved 1.7–2.0 times when given in the form of liposomes (F1 compared to griseofulvin suspension. Besides that, there was an approximately two-fold enhancement of the extent of bioavailability following administration of griseofulvin-loaded liposomes with higher encapsulation efficiency (F2, compared to those of F1. Also, the results showed that the extent of bioavailability of liposomal formulations with smaller sizes were higher by approximately three times compared to liposomal formulation of a larger size. Nevertheless, a further size reduction of griseofulvin-loaded liposome (≤400 nm did not promote the uptake or bioavailability of griseofulvin. In conclusion, high drug encapsulation efficiency and small liposome size could enhance the oral bioavailability of griseofulvin-loaded liposomes and therefore these two parameters deserve careful consideration during formulation.

  13. Introduction to Neutron Coincidence Counter Design Based on Boron-10

    Energy Technology Data Exchange (ETDEWEB)

    Kouzes, Richard T.; Ely, James H.; Lintereur, Azaree T.; Siciliano, Edward R.

    2012-01-22

    The Department of Energy Office of Nonproliferation Policy (NA-241) is supporting the project 'Coincidence Counting With Boron-Based Alternative Neutron Detection Technology' at Pacific Northwest National Laboratory (PNNL) for development of an alternative neutron coincidence counter. The goal of this project is ultimately to design, build and demonstrate a boron-lined proportional tube based alternative system in the configuration of a coincidence counter. This report, providing background information for this project, is the deliverable under Task 1 of the project.

  14. Boronic acid-based autoligation of nucleic acids

    DEFF Research Database (Denmark)

    Barbeyron, R.; Vasseur, J.-J.; Smietana, M.;

    2013-01-01

    Abstract: The development of synthetic systems displaying dynamic and adaptive characteristics is a formidable challenge with wide applications from biotechnology to therapeutics. Recently, we described a dynamic and programmable nucleic acid-based system relying on the formation of reversible...... boronate internucleosidic linkages. The DNA- or RNA-templated system comprises a 5′-ended boronic acid probe connecting a 3′-ended ribonucleosidic oligonucleotide partner. To explore the dominant factors that control the reversible linkage, we synthesized a series of 3′-end modified ribonucleotidic strands...

  15. Inhibition of HIV Virus by Neutralizing Vhh Attached to Dual Functional Liposomes Encapsulating Dapivirine

    Science.gov (United States)

    Wang, Scarlet Xiaoyan; Michiels, Johan; Ariën, Kevin K.; New, Roger; Vanham, Guido; Roitt, Ivan

    2016-07-01

    Although highly active antiretroviral therapy (HAART) has greatly improved the life expectancy of HIV/AIDS patients, the treatment is not curative. It is a global challenge which fosters an urgent need to develop an effective drug or neutralizing antibody delivery approach for the prevention and treatment of this disease. Due to the low density of envelope spikes with restricted mobility present on the surface of HIV virus, which limit the antibody potency and allow virus mutation and escape from the immune system, it is important for a neutralizing antibody to form bivalent or multivalent bonds with the virus. Liposome constructs could fulfil this need due to the flexible mobility of the membrane with its attached antibodies and the capacity for drug encapsulation. In this study, we evaluated the neutralization activity of a range of liposome formulations in different sizes coated with anti-gp120 llama antibody fragments (Vhhs) conjugated via either non-covalent metal chelation or a covalent linkage. The non-covalent construct demonstrated identical binding affinity to HIV-1 envelope glycoprotein gp120 and neutralizing ability for HIV virus as free Vhh. Although covalently linked Vhh showed significant binding affinity to gp120, it unexpectedly had a lower neutralization potency. This may be due to the comparability in size of the viral and liposome particles restricting the number which can be bound to the liposome surface so involving only a fraction of the antibodies, whereas non-covalently attached antibodies dissociate from the surface after acting with gp120 and free the remainder to bind further viruses. Covalently conjugated Vhh might also trigger the cellular uptake of a liposome-virion complex. To explore the possible ability of the antibody-coated liposomes to have a further function, we encapsulated the hydrophobic antiviral drug dapivirine into both of the non-covalently and covalently conjugated liposome formulations, both of which revealed high

  16. Thermal conductivity of boron carbides

    Science.gov (United States)

    Wood, C.; Emin, D.; Gray, P. E.

    1985-01-01

    Knowledge of the thermal conductivity of boron carbide is necessary to evaluate its potential for high-temperature thermoelectric energy conversion applications. Measurements have been conducted of the thermal diffusivity of hot-pressed boron carbide BxC samples as a function of composition (x in the range from 4 to 9), temperature (300-1700 K), and temperature cycling. These data, in concert with density and specific-heat data, yield the thermal conductivities of these materials. The results are discussed in terms of a structural model that has been previously advanced to explain the electronic transport data. Some novel mechanisms for thermal conduction are briefly discussed.

  17. Application of liposomal technologies for delivery of platinum analogs in oncology.

    Science.gov (United States)

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

    2013-01-01

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

  18. Application of liposomal technologies for delivery of platinum analogs in oncology

    Science.gov (United States)

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

    2013-01-01

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

  19. Stimuli-Responsive Liposomes for Controlled Drug Delivery

    KAUST Repository

    Li, Wengang

    2014-09-01

    Liposomes are promising drug delivery vesicles due to their biodegradibility, large volume and biocompatibility towards both hydrophilic and hydrophobic drugs. They suffer, however, from poor stability which limits their use in controlled delivery applications. Herein, a novel method was devised for modification of liposomes with small molecules, polymers or nanoparticles to afford stimuli responsive systems that release on demand and stay relatively stable in the absence of the trigger.. This dissertation discusses thermosensitive, pH sensitive, light sensitive and magnetically triggered liposomes that have been prepared for controlled drug delivery application. RAFT polymerization was utilized for the preparation of thermosensitive liposomes (Cholesterol-PNIPAm) and acid-labile liposomes (DOPE-PAA). With low Mw Cholesterol-PNIPAm, the thermosensitive liposomes proved to be effective for controlled release and decreased the cytotoxicity of PNIPAm by eliciting the polymer doses. By crosslinking the DOPE-PAA on liposome surface with acid-labile diamine linkers, DOPE-PAA liposomes were verified to be sensitive at low pH. The effects of polymer structures (linear or hyperbranched) have also been studied for the stability and release properties of liposomes. Finally, a dual-responsive Au@SPIO embedded liposome hybrid (ALHs) was prepared with light-induced “on-and-off” function by photo-thermal process (visible light) and instant release properties triggered by alternating magnetic field, respectively. The ALH system would be further applied into the cellular imaging field as MRI contrast agent.

  20. Bladder uptake of liposomes after intravesical administration occurs by endocytosis.

    Directory of Open Access Journals (Sweden)

    Bharathi Raja Rajaganapathy

    Full Text Available Liposomes have been used therapeutically and as a local drug delivery system in the bladder. However, the exact mechanism for the uptake of liposomes by bladder cells is unclear. In the present study, we investigated the role of endocytosis in the uptake of liposomes by cultured human UROtsa cells of urothelium and rat bladder. UROtsa cells were incubated in serum-free media with liposomes containing colloidal gold particles for 2 h either at 37°C or at 4°C. Transmission Electron Microscopy (TEM images of cells incubated at 37°C found endocytic vesicles containing gold inside the cells. In contrast, only extracellular binding was noticed in cells incubated with liposomes at 4°C. Absence of liposome internalization at 4°C indicates the need of energy dependent endocytosis as the primary mechanism of entry of liposomes into the urothelium. Flow cytometry analysis revealed that the uptake of liposomes at 37°C occurs via clathrin mediated endocytosis. Based on these observations, we propose that clathrin mediated endocytosis is the main route of entry for liposomes into the urothelial layer of the bladder and the findings here support the usefulness of liposomes in intravesical drug delivery.

  1. Effect of chitosan coating on the characteristics of DPPC liposomes

    Directory of Open Access Journals (Sweden)

    Mohsen M. Mady

    2010-07-01

    Full Text Available Because it is both biocompatible and biodegradable, chitosan has been used to provide a protective capsule in new drug formulations. The present work reports on investigations into some of the physicochemical properties of chitosan-coated liposomes, including drug release rate, transmission electron microscopy (TEM, zeta potential and turbidity measurement. It was found that chitosan increases liposome stability during drug release. The coating of DPPC liposomes with a chitosan layer was confirmed by electron microscopy and the zeta potential of liposomes. The coating of liposomes by chitosan resulted in a marginal increase in the size of the liposomes, adding a layer of (92 ± 27.1 nm. The liposomal zeta potential was found to be increasingly positive as chitosan concentration increased from 0.1% to 0.3% (w/v, before stabilising at a relatively constant value. Turbidity studies revealed that the coating of DPPC liposomes with chitosan did not significantly modify the main phase transition temperature of DPPC at examined chitosan concentrations. The appropriate combination of liposomal and chitosan characteristics may produce liposomes with specific, prolonged and controlled release.

  2. Cryo-electron tomography of nanoparticle transmigration into liposome.

    Science.gov (United States)

    Le Bihan, Olivier; Bonnafous, Pierre; Marak, Laszlo; Bickel, Thomas; Trépout, Sylvain; Mornet, Stéphane; De Haas, Felix; Talbot, Hugues; Taveau, Jean-Christophe; Lambert, Olivier

    2009-12-01

    Nanoparticle transport across cell membrane plays a crucial role in the development of drug delivery systems as well as in the toxicity response induced by nanoparticles. As hydrophilic nanoparticles interact with lipid membranes and are able to induce membrane perturbations, hypothetic mechanisms based on membrane curvature or hole formation have been proposed for activating their transmigration. We report on the transport of hydrophilic silica nanoparticles into large unilamellar neutral DOPC liposomes via an internalization process. The strong adhesive interactions of lipid membrane onto the silica nanoparticle triggered liposome deformation until the formation of a curved neck. Then the rupture of this membrane neck led to the complete engulfment of the nanoparticle. Using cryo-electron tomography we determined 3D architectures of intermediate steps of this process unveiling internalized silica nanoparticles surrounded by a supported lipid bilayer. This engulfing process was achieved for a large range of particle size (from 30 to 200 nm in diameter). These original data provide interesting highlights for nanoparticle transmigration and could be applied to biotechnology development.

  3. Clinical overview on Lipoplatin: a successful liposomal formulation of cisplatin.

    Science.gov (United States)

    Boulikas, Teni

    2009-08-01

    Nanoparticle formulations for packaging existing drugs have been used to treat cancer. Lipoplatin is a liposomal cisplatin encapsulated into liposome nanoparticles of an average diameter of 110 nm. Lipoplatin has substantially reduced the renal toxicity, peripheral neuropathy, ototoxicity, myelotoxicity as well as nausea/vomiting and asthenia of cisplatin in Phase I, II and III clinical studies with enhanced or similar efficacy to cisplatin. During clinical development, 10- to 200-fold higher accumulation of Lipoplatin in solid tumors compared to adjacent normal tissue was found in patients. Targeting of tumor vasculature by Lipoplatin in animals suggested its antiangiogenesis potential and Lipoplatin was proposed to act like a double-sword: as chemotherapy and an antiangiogenesis drug. Lipoplatin has finished successfully one Phase III non-inferiority clinical study as first-line against NSCLC in its combination with paclitaxel showing statistically significant reduction in nephrotoxicity; two more Phase III studies are in progress, one in NSCLC with gemcitabine also showing noninferiority with reduced toxicity and another in squamous cell carcinoma of the head and neck with 5-fluorouracil. A registrational Phase II/III study against pancreatic cancer is in progress under the orphan drug status granted to Lipoplatin by the European Medicines Agency. Phase II studies are continuing in advanced breast cancer with vinorelbine and gastrointestinal cancers with radiotherapy and 5-fluorouracil. The highlights of the clinical development of Lipoplatin are reviewed.

  4. Two-dimensional self-organization of the light-harvesting polypeptides/BChl a complex into a thermostable liposomal membrane

    NARCIS (Netherlands)

    Iida, K; Kiriyama, H; Fukai, A; Konings, WN; Nango, M

    2001-01-01

    The detergent-isolated light-harvesting polypeptide (LR)/bacteriochlorophyll alpha (BChl alpha) complex from the photosynthetic bacterium Rhodospirillum rubrum was organized in thermostable liposomal membranes comprising membrane-spanning tetraether lipids from Sulfolobus acidocaldarius to develop a

  5. Neutron beam monitor based on a boron-coated GEM

    Institute of Scientific and Technical Information of China (English)

    周健荣; 李仪; 孙志嘉; 刘贲; 王艳凤; 杨桂安; 周良; 许虹; 董静; 杨雷

    2011-01-01

    A new thermal neutron beam monitor with a Gas Electron Multiplier (GEM) is developed to meet the needs of the next generation of neutron facilities. A prototype chamber has been constructed with two 100 mm×100 mm GEM foils. Enriched boron-10 is coated on

  6. Preparation and evaluation of liposomal formulations of tropicamide for ocular delivery.

    Science.gov (United States)

    Nagarsenker, M S; Londhe, V Y; Nadkarni, G D

    1999-11-10

    Tropicamide, a mydriatic, cycloplegic drug was entrapped in liposomes. Liposomes were investigated by laser counting studies, transmission electron microscopy and differential scanning calorimetry for characterization. The precorneal clearance of liposomes was compared with solution by gamma-scintigraphy in the rabbit. The neutral liposomes failed to demonstrate significant enhancement in precorneal retention in comparison with aqueous solution. The potential of liposomes as an ophthalmic drug delivery system was investigated by comparing pupil dilatory effect of tropicamide by topical instillation, in the rabbit eye, of the solution and various drug-loaded liposomal forms, i.e. neutral liposomes, positively charged liposomes and neutral liposomes dispersed in 0.25% (w/v) polycarbophil gel. The positively charged liposomal formulation and liposomes dispersed in polycarbophil gel were found to be more effective than neutral liposomal dispersion when data were statistically treated at the 5% level of significance.

  7. Boron containing poly-(lactide-co-glycolide) (PLGA) scaffolds for bone tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Doğan, Ayşegül; Demirci, Selami [Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Yeditepe University 34755 Istanbul (Turkey); Bayir, Yasin [Department of Biochemistry, Faculty of Pharmacy, Ataturk University, 25240, Erzurum (Turkey); Halici, Zekai [Department of Pharmacology, Faculty of Medicine, Ataturk University, 25240, Erzurum (Turkey); Karakus, Emre [Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Ataturk University, 25240, Erzurum (Turkey); Aydin, Ali [Department of Orthopedics and Traumatology, Faculty of Medicine, Ataturk University, 25240, Erzurum (Turkey); Cadirci, Elif [Department of Pharmacology, Faculty of Pharmacy, Ataturk University, 25240, Erzurum (Turkey); Albayrak, Abdulmecit [Department of Pharmacology, Faculty of Medicine, Ataturk University, 25240, Erzurum (Turkey); Demirci, Elif [Department of Pathology, Faculty of Medicine, Ataturk University, 25240, Erzurum (Turkey); Karaman, Adem [Department of Radiology, Faculty of Medicine, Ataturk University, 25240, Erzurum (Turkey); Ayan, Arif Kursat [Department of Nuclear Medicine, Faculty of Medicine, Ataturk University, 25240, Erzurum (Turkey); Gundogdu, Cemal [Department of Pathology, Faculty of Medicine, Ataturk University, 25240, Erzurum (Turkey); Şahin, Fikrettin, E-mail: fsahin@yeditepe.edu.tr [Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Yeditepe University 34755 Istanbul (Turkey)

    2014-11-01

    Scaffold-based bone defect reconstructions still face many challenges due to their inadequate osteoinductive and osteoconductive properties. Various biocompatible and biodegradable scaffolds, combined with proper cell type and biochemical signal molecules, have attracted significant interest in hard tissue engineering approaches. In the present study, we have evaluated the effects of boron incorporation into poly-(lactide-co-glycolide-acid) (PLGA) scaffolds, with or without rat adipose-derived stem cells (rADSCs), on bone healing in vitro and in vivo. The results revealed that boron containing scaffolds increased in vitro proliferation, attachment and calcium mineralization of rADSCs. In addition, boron containing scaffold application resulted in increased bone regeneration by enhancing osteocalcin, VEGF and collagen type I protein levels in a femur defect model. Bone mineralization density (BMD) and computed tomography (CT) analysis proved that boron incorporated scaffold administration increased the healing rate of bone defects. Transplanting stem cells into boron containing scaffolds was found to further improve bone-related outcomes compared to control groups. Additional studies are highly warranted for the investigation of the mechanical properties of these scaffolds in order to address their potential use in clinics. The study proposes that boron serves as a promising innovative approach in manufacturing scaffold systems for functional bone tissue engineering. - Highlights: • Boron containing PLGA scaffolds were developed for bone tissue engineering. • Boron incorporation increased cell viability and mineralization of stem cells. • Boron containing scaffolds increased bone-related protein expression in vivo. • Implantation of stem cells on boron containing scaffolds improved bone healing.

  8. Emergence of liposome as targeted magic bullet for inflammatory disorders: current state of the art.

    Science.gov (United States)

    Rahman, Mahfoozur; Kumar, Vikas; Beg, Sarwar; Sharma, Gajanand; Katare, Om Prakash; Anwar, Firoz

    2016-11-01

    Inflammatory diseases are considered to be highly dreadful ones responsible for higher mortality in the developed countries. This includes cancer, psoriasis, rheumatoid arthritis, and inflammatory bowel disease. The tremendous strides in the area of drug development to find newer molecules like non-steroidal and steroidal agents and immunosuppressant agents delivered by conventional formulation. These therapy have enhances the life expectancy of patient, but it provide the therapeutic benefits only to a limited extent. Recent advancement in liposomes based nanomedicines has led to the possibility of improves the efficacy and safety of the pharmacotherapy of inflammatory disorders. Of late, liposomes have been highly explored as one of the promising systems for delivering numerous anti-inflammatory drugs for attaining enhanced therapeutic outcomes. Over the conventional carriers, liposomal systems have numerous drug delivery merits including advantages in both passive and active targeting of drug molecules to the inflammatory lesions. The current review article, therefore, endeavors to provide a bird's eye view account on the success of liposome-based therapeutic systems in the management of dreadful inflammatory disorders along with updated knowledge to pharmaceutical scientists in the field.

  9. Effects of boron on structure and antioxidative activities of spleen in rats.

    Science.gov (United States)

    Hu, Qianqian; Li, Shenghe; Qiao, Enmei; Tang, Zhongtao; Jin, Erhui; Jin, Guangming; Gu, Youfang

    2014-04-01

    In order to determine the relationship between boron and development of the spleen, especially in the promoting biological effects, we examined the effects of different levels of boron on weight, organ index, microstructure, and antioxidative activities of the spleen in rats. Sprague-Dawley (SD) rats were selected and treated with different concentrations of boron, and then, the organs were resected and weighed. One half of the tissue was fixed and embedded in paraffin to observe tissue structure changes. The other half of the tissue was homogenated for determining the antioxidant activities. The results showed that 40 mg/L of boron could increase weight, organ indexes, and antioxidant capacity of spleens and improve the spleen tissue structure, while the boron concentration above 80 mg/L could decrease weight, organ indexes, and antioxidant capacity of spleens and damage the spleen tissue structure. The higher the concentration, the more serious the damage was. Especially at the concentration of 640 mg/L, it could significantly inhibit the development of the spleen and even exhibit toxic effect. Hence, low boron concentration played a protective role in the development of the spleen, while high boron concentration could damage the organs and even produce toxic effect.

  10. Delivery of recombinant vaccines against bovine herpesvirus type 1 gD and Babesia bovis MSA-2c to mice using liposomes derived from egg yolk lipids.

    Science.gov (United States)

    Rodriguez, Anabel E; Zamorano, Patricia; Wilkowsky, Silvina; Torrá, Florencia; Ferreri, Lucas; Dominguez, Mariana; Florin-Christensen, Mónica

    2013-06-01

    Liposomes prepared from total egg yolk lipid extracts were used to deliver experimental DNA vaccines to mice consisting of pCI-neo plasmids encoding bovine herpesvirus type 1 (BoHV-1) gD or Babesia bovis MSA-2c. A significantly higher proportion of mice in the B. bovis MSA-2c group, but not those in the BoHV-1 gD group, developed detectable immunoglobulin G responses when vaccinated with liposome encapsulated DNA in comparison with mice vaccinated with naked DNA. In both groups, antibody titres were similar between mice vaccinated with liposome encapsulated DNA and naked DNA.

  11. Advanced microstructure of boron carbide.

    Science.gov (United States)

    Werheit, Helmut; Shalamberidze, Sulkhan

    2012-09-26

    The rhombohedral elementary cell of the complex boron carbide structure is composed of B(12) or B(11)C icosahedra and CBC, CBB or B□B (□, vacancy) linear arrangements, whose shares vary depending on the actual chemical compound. The evaluation of the IR phonon spectra of isotopically pure boron carbide yields the quantitative concentrations of these components within the homogeneity range. The structure formula of B(4.3)C at the carbon-rich limit of the homogeneity range is (B(11)C) (CBC)(0.91) (B□B)(0.09) (□, vacancy); and the actual structure formula of B(13)C(2) is (B(12))(0.5)(B(11)C)(0.5)(CBC)(0.65)(CBB)(0.16) (B□B)(0.19), and deviates fundamentally from (B(12))CBC, predicted by theory to be the energetically most favourable structure of boron carbide. In reality, it is the most distorted structure in the homogeneity range. The spectra of (nat)B(x)C make it evident that boron isotopes are not randomly distributed in the structure. However, doping with 2% silicon brings about a random distribution.

  12. Boronic acids for fluorescence imaging of carbohydrates.

    Science.gov (United States)

    Sun, Xiaolong; Zhai, Wenlei; Fossey, John S; James, Tony D

    2016-02-28

    "Fluorescence imaging" is a particularly exciting and rapidly developing area of research; the annual number of publications in the area has increased ten-fold over the last decade. The rapid increase of interest in fluorescence imaging will necessitate the development of an increasing number of molecular receptors and binding agents in order to meet the demand in this rapidly expanding area. Carbohydrate biomarkers are particularly important targets for fluorescence imaging given their pivotal role in numerous important biological events, including the development and progression of many diseases. Therefore, the development of new fluorescent receptors and binding agents for carbohydrates is and will be increasing in demand. This review highlights the development of fluorescence imaging agents based on boronic acids a particularly promising class of receptors given their strong and selective binding with carbohydrates in aqueous media.

  13. Advances and Challenges of Liposome Assisted Drug Delivery

    Directory of Open Access Journals (Sweden)

    Lisa eSercombe

    2015-12-01

    Full Text Available The application of liposomes to assist drug delivery has already had a major impact on many biomedical areas. They have been shown to be beneficial for stabilizing therapeutic compounds, overcoming obstacles to cellular and tissue uptake, and improving biodistribution of compounds to target sites in vivo. This enables effective delivery of encapsulated compounds to target sites while minimizing systemic toxicity. Liposomes present as an attractive delivery system due to their flexible physicochemical and biophysical properties, which allow easy manipulation to address different delivery considerations. Despite considerable research in the last 50 years and the plethora of positive results in preclinical studies, the clinical translation of liposome assisted drug delivery platforms has progressed incrementally. In this review, we will discuss the advances in liposome assisted drug delivery, biological challenges that still remain, and current clinical and experimental use of liposomes for biomedical applications. The translational obstacles of liposomal technology will also be presented.

  14. Liposomal Antioxidants for Protection against Oxidant-Induced Damage

    Directory of Open Access Journals (Sweden)

    Zacharias E. Suntres

    2011-01-01

    Full Text Available Reactive oxygen species (ROS, including superoxide anion, hydrogen peroxide, and hydroxyl radical, can be formed as normal products of aerobic metabolism and can be produced at elevated rates under pathophysiological conditions. Overproduction and/or insufficient removal of ROS result in significant damage to cell structure and functions. In vitro studies showed that antioxidants, when applied directly and at relatively high concentrations to cellular systems, are effective in conferring protection against the damaging actions of ROS, but results from animal and human studies showed that several antioxidants provide only modest benefit and even possible harm. Antioxidants have yet to be rendered into reliable and safe therapies because of their poor solubility, inability to cross membrane barriers, extensive first-pass metabolism, and rapid clearance from cells. There is considerable interest towards the development of drug-delivery systems that would result in the selective delivery of antioxidants to tissues in sufficient concentrations to ameliorate oxidant-induced tissue injuries. Liposomes are biocompatible, biodegradable, and nontoxic artificial phospholipid vesicles that offer the possibility of carrying hydrophilic, hydrophobic, and amphiphilic molecules. This paper focus on the use of liposomes for the delivery of antioxidants in the prevention or treatment of pathological conditions related to oxidative stress.

  15. Microfluidic manufacture of rt-PA-loaded echogenic liposomes

    Science.gov (United States)

    Kandadai, Madhuvanthi A.; Mukherjee, Prithviraj; Shekhar, Himanshu; Shaw, George J.; Papautsky, Ian; Holland, Christy K.

    2016-01-01

    Echogenic liposomes (ELIP), loaded with recombinant tissue-type plasminogen activator (rt-PA) and microbubbles that act as cavitation nuclei, are under development for ultrasound-mediated thrombolysis. Conventional manufacturing techniques produce a polydisperse rt-PA-loaded ELIP population with only a small percentage of particles containing microbubbles. Further, a polydisperse population of rt-PA-loaded ELIP has a broadband frequency response with complex bubble dynamics when exposed to pulsed ultrasound. In this work, a microfluidic flow-focusing device was used to generate monodisperse rt-PA-loaded ELIP (µtELIP) loaded with a perfluorocarbon gas. The rt-PA associated with the µtELIP was encapsulated within the lipid shell as well as intercalated within the lipid shell. The µtELIP had a mean diameter of 5 µm, a resonance frequency of 2.2 MHz, and were found to be stable for at least 30 min in 0.5%bovine serum albumin. Additionally, 35 % of µtELIP particles were estimated to contain microbubbles, an order of magnitude higher than that reported previously for batch-produced rt-PA-loaded ELIP. These findings emphasize the advantages offered by microfluidic techniques for improving the encapsulation efficiency of both rt-PA and perflurocarbon microbubbles within echogenic liposomes. PMID:27206512

  16. The levels of boron-uptake proteins in roots are correlated with tolerance to boron stress in barley

    Science.gov (United States)

    Boron (B) is an essential micronutrient required for plant growth and development. Recently, two major B-uptake proteins, BOR1 and NIP5;1 have been identified and partially characterized. BOR1 is a high-affinity B transporter involved in xylem loading in roots, and NIP5;1 acts is a major boric-acid ...

  17. Friction anisotropy in boronated graphite

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, N., E-mail: niranjan@igcar.gov.in [Materials Science Group, Indira Gandhi Centre for Atomic Research, Kalpakkam (India); Radhika, R. [Crystal Growth Centre, Anna University, Chennai (India); Kozakov, A.T. [Research Institute of Physics, Southern Federal University, Rostov-on-Don (Russian Federation); Pandian, R. [Materials Science Group, Indira Gandhi Centre for Atomic Research, Kalpakkam (India); Chakravarty, S. [UGC-DAE CSR, Kalpakkam (India); Ravindran, T.R.; Dash, S.; Tyagi, A.K. [Materials Science Group, Indira Gandhi Centre for Atomic Research, Kalpakkam (India)

    2015-01-01

    Graphical abstract: - Highlights: • Friction anisotropy in boronated graphite is observed in macroscopic sliding condition. • Low friction coefficient is observed in basal plane and becomes high in prismatic direction. • 3D phase of boronated graphite transformed into 2D structure after friction test. • Chemical activity is high in prismatic plane forming strong bonds between the sliding interfaces. - Abstract: Anisotropic friction behavior in macroscopic scale was observed in boronated graphite. Depending upon sliding speed and normal loads, this value was found to be in the range 0.1–0.35 in the direction of basal plane and becomes high 0.2–0.8 in prismatic face. Grazing-incidence X-ray diffraction analysis shows prominent reflection of (0 0 2) plane at basal and prismatic directions of boronated graphite. However, in both the wear tracks (1 1 0) plane become prominent and this transformation is induced by frictional energy. The structural transformation in wear tracks is supported by micro-Raman analysis which revealed that 3D phase of boronated graphite converted into a disordered 2D lattice structure. Thus, the structural aspect of disorder is similar in both the wear tracks and graphite transfer layers. Therefore, the crystallographic aspect is not adequate to explain anisotropic friction behavior. Results of X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy shows weak signature of oxygen complexes and functional groups in wear track of basal plane while these species dominate in prismatic direction. Abundance of these functional groups in prismatic plane indicates availability of chemically active sites tends to forming strong bonds between the sliding interfaces which eventually increases friction coefficient.

  18. Analysis of gemcitabine liposome injection by HPLC with evaporative light scattering detection.

    Science.gov (United States)

    Zhou, Qinmei; Liu, Liucheng; Zhang, Dengshan; Fan, XingFeng

    2012-12-01

    Gemcitabine liposome injection (i.e., stealth liposomes) has facilitated the targeting of gemcitabine for cancer treatment. We systemically reviewed liposome-based drug-delivery systems, which can improve pharmacokinetics, reduce side effects, and potentially increase tumor uptake, for pancreatic cancer therapy. A novel liposomal formulation, which allows for higher tumor-targeting efficiencies and can be used in current clinical trials to treat this challenging disease, has gained great popularity and attention. In this work, a simple, rapid high-performance liquid chromatography (HPLC) method was developed for the simultaneous determination of N-(carbonyl-methoxypolyethylene glycol 2000)-1, 2-distearoyl-sn-glycero-3-phosphoethanolamine sodium salt and neutral colipids cholesterol and hydrogenated soy phosphatidylcholine or distearoyl phosphatidylcholine. Because of the poor ultraviolet absorbance of the lipids, evaporative light-scattering detection (ELSD) was used to monitor the separation. The separation was carried out on a YMC-Pack column (YMC Co., Ltd., Kyoto, Japan). Lipids were eluted using binary linear gradients starting from a mixture of 80% A and 20% B to 100% B in 10 minutes, followed by a 6-minute plateau at 100% B, where A is chloroform/isopropyl alcohol/diethylamine/trifluoroacetic acid (TFA) (50:50:0.01:0.0025) and B is chloroform/isopropyl alcohol/H₂O/diethylamine/TFA (41:50:9:0.01:0.0025). The mobile phase composition was then changed back to initial solvent mixture in 1 minute, and the column was equilibrated for 13 minutes before every subsequent run. Then, 0.025% (v/v) TFA was added into the mobile phase to enhance the retaining of the stealth lipids. This newly developed method enabled direct analysis of liposomes without solvent lipid extraction and was validated to be linear, precise, accurate, specific, and sensitive. The method has been successfully employed in a wide range of lipid-based formulation screening, process development, and

  19. Liposome clusters with shear stress-induced membrane permeability.

    Science.gov (United States)

    Yoshimoto, Makoto; Tamura, Ryota; Natsume, Tomotaka

    2013-09-01

    Clusters of negatively charged liposomes were prepared by the addition of Ca(2+) and characterized in their structure and membrane permeability under shear stress. The liposomes mainly used were composed of zwitterionic 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), 20 mol% negatively charged 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPG) and 30 mol% cholesterol. The liposomes with mean diameter of 193 nm were aggregated into the clusters with a distribution peak at about 1.5 μm in the 50mM Tris buffer solution of pH 8.5 at the lipid and Ca(2+) concentrations of 1.0mM and 40 mM, respectively. More than 90% of liposomes were redispersed at the Ca(2+) concentration of 80 mM. POPG-rich liposomes (POPC/POPG/cholesterol=5:65:30 [lipid]=1.0mM) were irreversibly aggregated at [Ca(2+)]≥ 10 mM, indicating the significant contribution of POPC to the reversible clustering of liposomes. The membranes of liposome clusters were impermeable to 5(6)-carboxyfluorescein (CF) in the static liquid system at 25°C due to the decrease in specific surface area of the liposomal system. In the shear flow, in clear contrast, continuous membrane permeation of CF was observed at the shear rate of 1.5 × 10(3)s(-1), exhibiting comparable membrane permeability to the non-clustered liposomes. The theoretical analysis of modified DLVO potential indicated that liposome membranes were not in contact with each other within the clusters. Therefore, the liposome clusters are structurally flexible under the applied shear stress, providing sufficient lipid membrane-water interfacial area for the permeation of CF. The results obtained would be important to control the formation of liposome clusters and their permeabilization for biochemical and biomedical applications.

  20. Basic research of boron neutron-capture therapy for treatment of pancreatic cancer. Application of neutron radiography for visualization of boron compound on BNCT

    Energy Technology Data Exchange (ETDEWEB)

    Yanagie, Hironobu [Tokyo Univ. (Japan). Inst. of Medical Science

    1997-02-01

    The cytotoxic effects of locally injected {sup 10}B-immunoliposomes (anti-CEA) on human pancreatic carcinoma xenografts in nude mice were evaluated with thermal neutron irradiation. After thermal neutron irradiation of mice injected with {sup 10}B-immunoliposomes, AsPC-1 tumour growth was suppressed relative to controls. Histopathologically, hyalinization and necrosis were found in {sup 10}B-treated tumours, while tumour tissue injected with saline or saline-containing immunoliposomes showed neither destruction nor necrosis. These results suggest that intratumoral injection of boronated immunoliposomes can increase the retention of {sup 10}B atoms by tumour cells, causing tumour growth suppression in vivo upon thermal neutron irradiation. We prepared boronated PEG-binding bovine serum albumin ({sup 10}B-PEG-BSA). {sup 10}B concentrations in AsPC-1, human pancreatic cancer cells (2 x 10{sup 5} /well) obtained 24 hrs after incubation with {sup 10}B-PEG-BSA was 13.01 {+-} 1.74 ppm. The number of {sup 10}B atoms delivered to the tumor cells was calculated to be 7.83 x 10{sup 11} at 24 hrs after incubation with {sup 10}B-PEG-BSA. These data indicated that the {sup 10}B-PEG-BSA could deliver a sufficient amount of {sup 10}B atoms (more than 10{sup 9} atoms/cell) to the tumor cells to induce cytotoxic effects after incubation upon thermal neutron irradiation. Neutron capture autoradiography by using an Imaging Plate (IP-NCR) was performed on AsPC-1 tumor-bearing mouse that had been given an intratumoral injection of {sup 10}B-PEG BSA or {sup 10}B-cationic liposome. We had demonstrated the {sup 10}B-PEG BSA or {sup 10}B-cationic liposome is taken up by AsPC-1 tumor tissue to a much greater extent than by normal tissues. (J.P.N.)

  1. A study on zeta potential and dielectric constant of liposomes.

    Science.gov (United States)

    Labhasetwar, V; Mohan, M S; Dorle, A K

    1994-01-01

    Zeta potential and dielectric constant of the liposomes were measured to study the effect of some of the formulation factors and in vitro ageing. Sonication affects zeta potential and dielectric constant of the liposomes. The ageing study showed an increase in the dielectric constant and zeta potential of liposomes at different storage temperatures. These two electrical parameters could be useful in studying structural alterations in liposomal vesicles and system as a function of different conditions. Particle size distribution and optical density were also measured, for comparison.

  2. Application of long-circulating liposomes to cancer photodynamic therapy.

    Science.gov (United States)

    Oku, N; Saito, N; Namba, Y; Tsukada, H; Dolphin, D; Okada, S

    1997-06-01

    Photodynamic therapy (PDT) as a cancer treatment is notable for its quite low side effects in comparison with those of chemotherapy and radiotherapy. However, the accumulation of porphyrin derivatives used in PDT into tumor tissues is rather low. Since long-circulating liposomes are known to accumulate passively into tumor tissues, we liposomalized a porphyrin derivative, benzoporphyrin derivative monoacid ring A (BPD-MA), and used these liposomes to investigate the usefulness of PDT for tumor-bearing mice. BPD-MA was liposomalized into glucuronate-modified liposomes, which are known to be long-circulating. These liposomes were injected i.v. into Balb/c mice bearing Meth A sarcoma, and tumor regression and survival time were monitored after irradiation with laser light. Tumor regression and complete curing of tumor (80% cure rate by the treatment with 6 mg/kg BPD-MA) were observed when long circulating liposomalized BPD-MA was injected and laser-irradiated. In contrast, only a 20% cure rate was obtained when the animals were treated with BPD-MA solution or BPD-MA entrapped in conventional liposomes. These results suggest that a long-circulating liposomal formulation of photo-sensitive agents is useful for PDT.

  3. Characterization of sterically stabilized cisplatin liposomes by nuclear magnetic resonance.

    Science.gov (United States)

    Peleg-Shulman, T; Gibson, D; Cohen, R; Abra, R; Barenholz, Y

    2001-02-09

    Extensive scientific efforts are directed towards finding new and improved platinum anticancer agents. A promising approach is the encapsulation of cisplatin in sterically stabilized, long circulating, PEGylated 100 nm liposomes. This liposomal cisplatin (STEALTH cisplatin, formerly known as SPI-77) shows excellent stability in plasma and has a longer circulation time, greater efficacy and lower toxicity than much free cisplatin. However, so far, the physicochemical characterization of STEALTH cisplatin has been limited to size distribution, drug-to-lipid ratio and stability. Information on the physical state of the drug in the liposome aqueous phases and the drug's interaction with the liposome membrane has been lacking. This study was aimed at filling this gap. We report a multinuclear NMR study in which several techniques have been used to assess the physical nature of cisplatin in liposomal formulations and if and to what extent the drug affects the liposome phospholipids. Since NMR detects only the soluble cisplatin in the liposomes and not the insoluble drug, combining NMR and atomic absorption data enables one to determine how much of the encapsulated drug is soluble in the intraliposomal aqueous phase. Our results indicate that almost all of the cisplatin remains intact during the loading process, and that the entire liposomal drug is present in a soluble form in the internal aqueous phase of the liposomes.

  4. Liposomes and MTT cell viability assay: an incompatible affair.

    Science.gov (United States)

    Angius, Fabrizio; Floris, Alice

    2015-03-01

    The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay is commonly used to evaluate the cytotoxicity potential of drugs vehicled by liposomes. However, liposome delivering drugs could produce inconsistent values of MTT absorbance. On the basis of previous experiments demonstrating the MTT affinity for lipid droplets, this paper aims to show that empty-liposomes interfere, per se, on MTT assay due to its lipidic nature. This brings into question the use of MTT testing cytotoxicity when liposomes are involved in delivering drugs.

  5. [Effect of polyethylene glycol-lipid derivatives on the stability of grafted liposomes].

    Science.gov (United States)

    Xu, Yang; Shi, Li; Deng, Yi-hui

    2011-10-01

    It is reported that polyethylene glycol-lipid (PEG-lipid) derivatives increase liposomes stability, prolong the blood circulation of liposomes, enhance their tumor-targeting efficiency, and improve drug efficacy. Therefore, it is of great importance to investigate the influence of modified PEG-lipid derivatives on the physical, chemical, and biological characteristics of liposomes for the promotion of dealing with the existed problems, such as the accelerated blood clearance (ABC) phenomenon when repeated intravous injection at a certain time-interval, and developing novel targeted pharmaceutical preparations. In this review, the effects of modified PEG-lipid derivatives were summarized in many aspects. It indicats that the chemical bonds (amide, ether, ester, and disulfide) between PEG and lipid, as well as the species of lipids, such as the commonly used phosphatidylethanolamine, cholesterol, and diacylglycerol have substantial effects on the grafted liposomes stability in vitro and in vivo. Besides, the properties of lipids (the fatty acid chain length and saturation) and the groups (methoxy, carboxylic and amino) at the distal ends of the PEG chains were also considered to be important factors. In the end, the influence of the average molecular weight of PEG and the molar ratio of PEG-lipid derivatives in the total lipid were further focused.

  6. Hybrid liposomal PEGylated calix[4]arene systems as drug delivery platforms for curcumin.

    Science.gov (United States)

    Drakalska, Elena; Momekova, Denitsa; Manolova, Yana; Budurova, Dessislava; Momekov, Georgi; Genova, Margarita; Antonov, Liudmil; Lambov, Nikolay; Rangelov, Stanislav

    2014-09-10

    The tremendous therapeutic potential of curcumin as a chemopreventive, antineoplastic and chemosensitizing agent has failed to progress towards clinical development and commercialization due to its unfavorable physicochemical properties, low aqueous solubility, chemical instability, and pharmacokinetics. The present contribution is focused on the feasibility of using PEGylated calixarene, in particular polyoxyethylene-derivatized tert-butylcalix[4]arene, to prepare various platforms for delivery of curcumin such as inclusion complex, supramolecular aggregates, and hybrid liposomal systems. The inclusion complex is characterized by UV-vis and FT-IR spectroscopy as well as thermal gravimetrical analysis and differential scanning calorimetry. At concentrations exceeding the critical micellization concentration of PEGylated calixarene, the tremendous solubility enhancement of curcumin is attributed to additional solubilization and hydrophobic non-covalent interactions of the drug with supramolecular aggregates. A hybrid liposomal system is created via encapsulation of the inclusion complex in dipalmitoylphosphatidylcholine:cholesterol liposomes. Bare and liposomal curcumin:BEC-X inclusion complexes, as well as free curcumin were additionally investigated for cytotoxicity and apoptogenic activity against human tumor cell lines.

  7. An in vitro model to test relative antioxidant potential: Ultraviolet-induced lipid peroxidation in liposomes

    Energy Technology Data Exchange (ETDEWEB)

    Pelle, E.; Maes, D.; Padulo, G.A.; Kim, E.K.; Smith, W.P. (Estee Lauder Research and Development, Melville, NY (USA))

    1990-12-01

    Since antioxidants have been shown to play a major role in preventing some of the effects of aging and photoaging in skin, it is important to study this phenomenon in a controlled manner. This was accomplished by developing a simple and reliable in vitro technique to assay antioxidant efficacy. Inhibition of peroxidation by antioxidants was used as a measure of relative antioxidant potential. Liposomes, high in polyunsaturated fatty acids (PUFA), were dispersed in buffer and irradiated with ultraviolet (UV) light. Irradiated liposomes exhibited a significantly higher amount of hydroperoxides than liposomes containing antioxidants in a dose- and concentration-dependent manner. Lipid peroxidation was determined spectrophotometrically by an increase in thiobarbituric acid reacting substances. To further substantiate the production of lipid peroxides, gas chromatography was used to measure a decrease in PUFA substrate. In order of decreasing antioxidant effectiveness, the following results were found among lipophilic antioxidants: BHA greater than catechin greater than BHT greater than alpha-tocopherol greater than chlorogenic acid. Among hydrophilic antioxidants, ascorbic acid and dithiothreitol were effective while glutathione was ineffective. In addition, ascorbic acid was observed to act synergistically with alpha-tocopherol, which is in agreement with other published reports on the interaction of these two antioxidants. Although peroxyl radical scavengers seem to be at a selective advantage in this liposomal/UV system, these results demonstrate the validity of this technique as an assay for measuring an antioxidant's potential to inhibit UV-induced peroxidation.

  8. Protective effect of trehalose-loaded liposomes against UVB-induced photodamage in human keratinocytes

    Science.gov (United States)

    EMANUELE, ENZO; BERTONA, MARCO; SANCHIS-GOMAR, FABIAN; PAREJA-GALEANO, HELIOS; LUCIA, ALEJANDRO

    2014-01-01

    Trehalose, a naturally occurring non-reducing disaccharide, is known to act as a major protein stabilizer that can reduce ultraviolet B (UVB)-induced corneal damage when topically applied to the eye. However, due to the low skin permeability of trehalose, which makes the development of topical formulations difficult, its use as a skin photoprotective agent has been limited. Previous findings demonstrated that liposomes may significantly improve the intracellular delivery of trehalose. Therefore, the present study aimed to assess the protective effects of trehalose-loaded liposomes against UVB-induced photodamage using the immortalized human keratinocyte cell line, HaCaT. The effects were also compared to those of the common skin photoprotective compounds, including L-carnosine, L-(+)-ergothioneine, L-ascorbic acid and DL-α-tocopherol. The levels of cyclobutane pyrimidine dimers, 8-hydroxy-2′-deoxyguanosine and protein carbonylation in HaCaT cells were used as biological markers of UVB-induced damage. Compared to other compounds, trehalose-loaded liposomes showed the highest efficacy in reducing the levels of the three markers following UVB irradiation of HaCaT cells (all P<0.001 when compared to each of the four other photoprotective compounds). Therefore, these findings indicate that there may be a clinical application for trehalose-loaded liposomes, and further studies should be performed to assess the potential usefulness in skin photoprotection and the prevention of non-melanoma skin cancer. PMID:25054023

  9. Photodynamic action of hypocrellin A in liposomes

    Institute of Scientific and Technical Information of China (English)

    邹伟; 安静仪; 李滨; 蒋丽金

    1996-01-01

    Hypocrellin A (HA), a perylenequinone derivative, is an efficient phototherapeutic agent. When HA is incorporated into small unilamellar liposomes of egg phosphatidylcholine, it generates 1O2 as demonstrated by 9,10-diphenylanthracene (9,10-DPA) photobleaching and detection of nitroxide radicals with ESR. The 1O2 quantum yield measured is 0.80±0.02. On irradiation of oxygen-saturated solution of HA-liposomes, hydroxyl radical OH is detected using DMPO as the ESR spin trapping agent. Hydroxyl radical is derived from superoxide radical anion O2-. The electron transfer reaction is also studied in deaerated solution. The results suggest that the photodynamic action of HA in lipid membranes proceeds via both Type I and Type II reactions.

  10. Phase structure of liposome in lipid mixtures.

    Science.gov (United States)

    Zhang, Tianxi; Li, Yuzhuo; Mueller, Anja

    2011-11-01

    Gas microbubbles present in ultrasound imaging contrast agents are stabilized by lipid aggregates that typically contain a mixture of lipids. In this study, the phase structure of the lipid mixtures that contained two or three lipids was investigated using three different methods: dynamic light scattering, (1)H NMR, and microfluidity measurements with fluorescence probes. Three lipids that are commonly present in imaging agents (DPPC, DPPE-PEG, and DPPA) were used. Two types of systems, two-lipid model systems and simulated imaging systems were investigated. The results show that liposomes were the dominant aggregates in all the samples studied. The polar PEG side chains from the PEGylated lipid lead to the formation of micelles and micellar aggregates in small sizes. In the ternary lipid systems, almost all the lipids were present in bilayers with micelles absent and free lipids at very low concentration. These results suggest that liposomes, not micelles, contribute to the stabilization of microbubbles in an ultrasound imaging contrast agent.

  11. Influence of charge ratio of liposome/DNA complexes on their size after extrusion and transfection efficiency

    Directory of Open Access Journals (Sweden)

    Brgles M

    2012-01-01

    Full Text Available Marija Brgles, Maja Šantak, Beata Halassy, Dubravko Forcic, Jelka TomašicInstitute of Immunology, Research and Development Department, Zagreb, CroatiaBackground: Physicochemical characteristics of liposome/DNA complexes influence transfection efficiency and affect each other in a very intricate way. The result of this is discrepancies in conclusions drawn about the individual influence of each one.Methods: Aiming to elucidate the influence of liposome/DNA charge ratio and size on transfection efficiency and on each other, we used liposome/DNA complexes with charge ratio (+/- in the range of 1–50 and extruded through membranes of 400, 200, and 100 nm. Plasmid DNA encoding green fluorescent protein was used to measure transfection efficiency by flow cytometry. Sizes of liposome/DNA complexes were measured by dynamic light scattering.Results: Liposome size was reduced after extrusion but this was mainly driven by the charge ratio and not by the size of the membrane pores. Reduction of complex size at each charge ratio positively correlated with transfection efficiency. When the size of the complexes was approximately constant, increasing the charge ratio was found to promote transfection efficiency. Cationic lipid N-(1-(2,3-dioleoyloxypropylN,N,N trimethylammonium chloride was used for modulation of positive charge and a cytotoxicity test showed that increasing its amount increases cytotoxicity.Conclusion: It can be concluded that charge ratio dictates the size of the complex whereas overall size reduction and higher charge ratios promote transfection efficiency in vitro.Keywords: transfection efficiency, liposome charge, liposome size

  12. HER2-targeted liposomal doxorubicin displays enhanced anti-tumorigenic effects without associated cardiotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Reynolds, Joseph G.; Geretti, Elena; Hendriks, Bart S.; Lee, Helen; Leonard, Shannon C.; Klinz, Stephan G.; Noble, Charles O. [Merrimack Pharmaceuticals, 1 Kendall Square, Suite B7201, Cambridge, MA 02139 (United States); Lücker, Petra B.; Zandstra, Peter W. [University of Toronto, 160 College Street, Office 1116, Toronto, Ontario M5S 3E1 (Canada); Drummond, Daryl C.; Olivier, Kenneth J.; Nielsen, Ulrik B.; Niyikiza, Clet; Agresta, Samuel V. [Merrimack Pharmaceuticals, 1 Kendall Square, Suite B7201, Cambridge, MA 02139 (United States); Wickham, Thomas J., E-mail: twickham@merrimackpharma.com [Merrimack Pharmaceuticals, 1 Kendall Square, Suite B7201, Cambridge, MA 02139 (United States)

    2012-07-01

    Anthracycline-based regimens are a mainstay of early breast cancer therapy, however their use is limited by cardiac toxicity. The potential for cardiotoxicity is a major consideration in the design and development of combinatorial therapies incorporating anthracyclines and agents that target the HER2-mediated signaling pathway, such as trastuzumab. In this regard, HER2-targeted liposomal doxorubicin was developed to provide clinical benefit by both reducing the cardiotoxicity observed with anthracyclines and enhancing the therapeutic potential of HER2-based therapies that are currently available for HER2-overexpressing cancers. While documenting the enhanced therapeutic potential of HER2-targeted liposomal doxorubicin can be done with existing models, there has been no validated human cardiac cell-based assay system to rigorously assess the cardiotoxicity of anthracyclines. To understand if HER2-targeting of liposomal doxorubicin is possible with a favorable cardiac safety profile, we applied a human stem cell-derived cardiomyocyte platform to evaluate the doxorubicin exposure of human cardiac cells to HER2-targeted liposomal doxorubicin. To the best of our knowledge, this is the first known application of a stem cell-derived system for evaluating preclinical cardiotoxicity of an investigational agent. We demonstrate that HER2-targeted liposomal doxorubicin has little or no uptake into human cardiomyocytes, does not inhibit HER2-mediated signaling, results in little or no evidence of cardiomyocyte cell death or dysfunction, and retains the low penetration into heart tissue of liposomal doxorubicin. Taken together, this data ultimately led to the clinical decision to advance this drug to Phase I clinical testing, which is now ongoing as a single agent in HER2-expressing cancers. -- Highlights: ► Novel approach using stem cell-derived cardiomyocytes to assess preclinical safety. ► HER2-targeted liposomal doxorubicin has improved safety profile vs free doxorubicin

  13. Pegylated liposomal doxorubicin in ovarian cancer

    OpenAIRE

    Matei, Daniela

    2009-01-01

    Robert Strother1,2, Daniela Matei1–51Department of Medicine, 2Indiana University Melvin and Bren Simon Cancer Center, 3Department of Obstetrics and Gynecology, 4Department of Biochemistry and Molecular Biology, 5VA Roudebush Hospital Indiana University School of Medicine, 535 Barnhill Drive, Indianapolis, IN, 46202Abstract: The encapsulation of doxorubicin in a pegylated liposomal matrix led to a reformulated agent with a different toxicity profile and improved clinical utility. Lip...

  14. Boron Neutron Capture Therapy for Malignant Brain Tumors

    Science.gov (United States)

    MIYATAKE, Shin-Ichi; KAWABATA, Shinji; HIRAMATSU, Ryo; KUROIWA, Toshihiko; SUZUKI, Minoru; KONDO, Natsuko; ONO, Koji

    2016-01-01

    Boron neutron capture therapy (BNCT) is a biochemically targeted radiotherapy based on the nuclear capture and fission reactions that occur when non-radioactive boron-10, which is a constituent of natural elemental boron, is irradiated with low energy thermal neutrons to yield high linear energy transfer alpha particles and recoiling lithium-7 nuclei. Therefore, BNCT enables the application of a high dose of particle radiation selectively to tumor cells in which boron-10 compound has been accumulated. We applied BNCT using nuclear reactors for 167 cases of malignant brain tumors, including recurrent malignant gliomas, newly diagnosed malignant gliomas, and recurrent high-grade meningiomas from January 2002 to May 2014. Here, we review the principle and history of BNCT. In addition, we introduce fluoride-18-labeled boronophenylalanine positron emission tomography and the clinical results of BNCT for the above-mentioned malignant brain tumors. Finally, we discuss the recent development of accelerators producing epithermal neutron beams. This development could provide an alternative to the current use of specially modified nuclear reactors as a neutron source, and could allow BNCT to be performed in a hospital setting. PMID:27250576

  15. Boron Neutron Capture Therapy for Malignant Brain Tumors.

    Science.gov (United States)

    Miyatake, Shin-Ichi; Kawabata, Shinji; Hiramatsu, Ryo; Kuroiwa, Toshihiko; Suzuki, Minoru; Kondo, Natsuko; Ono, Koji

    2016-07-15

    Boron neutron capture therapy (BNCT) is a biochemically targeted radiotherapy based on the nuclear capture and fission reactions that occur when non-radioactive boron-10, which is a constituent of natural elemental boron, is irradiated with low energy thermal neutrons to yield high linear energy transfer alpha particles and recoiling lithium-7 nuclei. Therefore, BNCT enables the application of a high dose of particle radiation selectively to tumor cells in which boron-10 compound has been accumulated. We applied BNCT using nuclear reactors for 167 cases of malignant brain tumors, including recurrent malignant gliomas, newly diagnosed malignant gliomas, and recurrent high-grade meningiomas from January 2002 to May 2014. Here, we review the principle and history of BNCT. In addition, we introduce fluoride-18-labeled boronophenylalanine positron emission tomography and the clinical results of BNCT for the above-mentioned malignant brain tumors. Finally, we discuss the recent development of accelerators producing epithermal neutron beams. This development could provide an alternative to the current use of specially modified nuclear reactors as a neutron source, and could allow BNCT to be performed in a hospital setting.

  16. Liposomes as lubricants: beyond drug delivery.

    Science.gov (United States)

    Goldberg, Ronit; Klein, Jacob

    2012-05-01

    In this paper we review recent work (Goldberg et al., 2011a,b) on a new use for phosphatidylcholine liposomes: as ultra-efficient boundary lubricants at up to the highest physiological pressures. Using a surface force balance, we have measured the normal and shear interactions as a function of surface separation between layers of hydrogenated soy phophatidylcholine (HSPC) small unilamellar vesicles (SUVs) adsorbed from dispersion, at both pure water and physiologically high salt concentrations of 0.15 M NaNO(3). Cryo-Scanning Electron Microscopy shows each surface to be coated by a close-packed HSPC-SUV layer with an over-layer of liposomes on top. The shear forces reveal strikingly low friction coefficients down to 2×10(-5) in pure water system or 6×10(-4) in the 150 mM salt system, up to contact pressures of at least 12 MPa (pure water) or 6 MPa (high salt), comparable with those in the major joints. This low friction is attributed to the hydration lubrication mechanism arising from rubbing of the highly hydrated phosphocholine-headgroup layers exposed at the outer surface of each liposome, and provides support for the conjecture that phospholipids may play a significant role in biological lubrication.

  17. Getting into the brain: liposome-based strategies for effective drug delivery across the blood-brain barrier.

    Science.gov (United States)

    Vieira, Débora B; Gamarra, Lionel F

    This review summarizes articles that have been reported in literature on liposome-based strategies for effective drug delivery across the blood-brain barrier. Due to their unique physicochemical characteristics, liposomes have been widely investigated for their application in drug delivery and in vivo bioimaging for the treatment and/or diagnosis of neurological diseases, such as Alzheimer's, Parkinson's, stroke, and glioma. Several strategies have been used to deliver drug and/or imaging agents to the brain. Covalent ligation of such macromolecules as peptides, antibodies, and RNA aptamers is an effective method for receptor-targeting liposomes, which allows their blood-brain barrier penetration and/or the delivery of their therapeutic molecule specifically to the disease site. Additionally, methods have been employed for the development of liposomes that can respond to external stimuli. It can be concluded that the development of liposomes for brain delivery is still in its infancy, although these systems have the potential to revolutionize the ways in which medicine is administered.

  18. High-efficiency liposomal encapsulation of a tyrosine kinase inhibitor leads to improved in vivo toxicity and tumor response profile.

    Science.gov (United States)

    Mukthavaram, Rajesh; Jiang, Pengfei; Saklecha, Rohit; Simberg, Dmitri; Bharati, Ila Sri; Nomura, Natsuko; Chao, Ying; Pastorino, Sandra; Pingle, Sandeep C; Fogal, Valentina; Wrasidlo, Wolf; Makale, Milan; Kesari, Santosh

    2013-01-01

    Staurosporine (STS) is a potent pan-kinase inhibitor with marked activity against several chemotherapy-resistant tumor types in vitro. The translational progress of this compound has been hindered by poor pharmacokinetics and toxicity. We sought to determine whether liposomal encapsulation of STS would enhance antitumor efficacy and reduce toxicity, thereby supporting the feasibility of further preclinical development. We developed a novel reverse pH gradient liposomal loading method for STS, with an optimal buffer type and drug-to-lipid ratio. Our approach produced 70% loading efficiency with good retention, and we provide, for the first time, an assessment of the in vivo antitumor activity of STS. A low intravenous dose (0.8 mg/kg) inhibited U87 tumors in a murine flank model. Biodistribution showed preferential tumor accumulation, and body weight data, a sensitive index of STS toxicity, was unaffected by liposomal STS, but did decline with the free compound. In vitro experiments revealed that liposomal STS blocked Akt phosphorylation, induced poly(ADP-ribose) polymerase cleavage, and produced cell death via apoptosis. This study provides a basis to explore further the feasibility of liposomally encapsulated STS, and potentially related compounds for the management of resistant solid tumors.

  19. Boron-10 ABUNCL Prototype Initial Testing

    Energy Technology Data Exchange (ETDEWEB)

    Kouzes, Richard T.; Ely, James H.; Lintereur, Azaree T.; Siciliano, Edward R.

    2012-12-01

    The Department of Energy Office of Nuclear Safeguards and Security (NA-241) is supporting the project Coincidence Counting With Boron-Based Alternative Neutron Detection Technology at Pacific Northwest National Laboratory (PNNL) for the development of a 3He proportional counter alternative neutron coincidence counter. The goal of this project is to design, build and demonstrate a system based upon 10B-lined proportional tubes in a configuration typical for 3He-based coincidence counter applications. This report provides results of initial testing of an Alternative Boron-Based Uranium Neutron Coincidence Collar (ABUNCL) design built by General Electric Reuter-Stokes. Several configurations of the ABUNCL models, which use 10B-lined proportional counters in place of 3He proportional counters for the neutron detection elements, were previously reported. The ABUNCL tested is of a different design than previously modeled. Initial experimental testing of the as-delivered passive ABUNCL was performed, and modeling will be conducted. Testing of the system reconfigured for active testing will be performed in the near future, followed by testing with nuclear fuel.

  20. Jaguar Procedures for Detonation Behavior of Explosives Containing Boron

    Science.gov (United States)

    Stiel, L. I.; Baker, E. L.; Capellos, C.

    2009-12-01

    The Jaguar product library was expanded to include boron and boron containing products by analysis of Available Hugoniot and static volumetric data to obtain constants of the Murnaghan relationships for the components. Experimental melting points were also utilized to obtain the constants of the volumetric relationships for liquid boron and boron oxide. Detonation velocities for HMX—boron mixtures calculated with these relationships using Jaguar are in closer agreement with literature values at high initial densities for inert (unreacted) boron than with the completely reacted metal. These results indicate that the boron does not react near the detonation front or that boron mixtures exhibit eigenvalue detonation behavior (as shown by some aluminized explosives), with higher detonation velocities at the initial points. Analyses of calorimetric measurements for RDX—boron mixtures indicate that at high boron contents the formation of side products, including boron nitride and boron carbide, inhibits the detonation properties of the formulation.

  1. Electrochemical Corrosion Behavior of Spray-Formed Boron-Modified Supermartensitic Stainless Steel

    Science.gov (United States)

    Zepon, Guilherme; Nogueira, Ricardo P.; Kiminami, Claudio S.; Botta, Walter J.; Bolfarini, Claudemiro

    2017-04-01

    Spray-formed boron-modified supermartensitic stainless steel (SMSS) grades are alloys developed to withstand severe wear conditions. The addition of boron to the conventional chemical composition of SMSS, combined with the solidification features promoted by the spray forming process, leads to a microstructure composed of low carbon martensitic matrix reinforced by an eutectic network of M2B-type borides, which considerably increases the wear resistance of the stainless steel. Although the presence of borides in the microstructure has a very beneficial effect on the wear properties of the alloy, their effect on the corrosion resistance of the stainless steel was not comprehensively evaluated. The present work presents a study of the effect of boron addition on the corrosion resistance of the spray-formed boron-modified SMSS grades by means of electrochemical techniques. The borides fraction seems to have some influence on the repassivation kinetics of the spray-formed boron-modified SMSS. It was shown that the Cr content of the martensitic matrix is the microstructural feature deciding the corrosion resistance of this sort of alloys. Therefore, if the Cr content in the alloy is increased to around 14 wt pct to compensate for the boron consumed by the borides formation, the corrosion resistance of the alloy is kept at the same level of the alloy without boron addition.

  2. Silver Nanoparticle-Deposited Boron Nitride Nanosheets as Fillers for Polymeric Composites with High Thermal Conductivity.

    Science.gov (United States)

    Wang, Fangfang; Zeng, Xiaoliang; Yao, Yimin; Sun, Rong; Xu, Jianbin; Wong, Ching-Ping

    2016-01-19

    Polymer composites with high thermal conductivity have recently attracted much attention, along with the rapid development of the electronic devices toward higher speed and performance. However, a common method to enhance polymer thermal conductivity through an addition of high thermally conductive fillers usually cannot provide an expected value, especially for composites requiring electrical insulation. Here, we show that polymeric composites with silver nanoparticle-deposited boron nitride nanosheets as fillers could effectively enhance the thermal conductivity of polymer, thanks to the bridging connections of silver nanoparticles among boron nitride nanosheets. The thermal conductivity of the composite is significantly increased from 1.63 W/m-K for the composite filled with the silver nanoparticle-deposited boron nitride nanosheets to 3.06 W/m-K at the boron nitride nanosheets loading of 25.1 vol %. In addition, the electrically insulating properties of the composite are well preserved. Fitting the measured thermal conductivity of epoxy composite with one physical model indicates that the composite with silver nanoparticle-deposited boron nitride nanosheets outperforms the one with boron nitride nanosheets, owning to the lower thermal contact resistance among boron nitride nanosheets' interfaces. The finding sheds new light on enhancement of thermal conductivity of the polymeric composites which concurrently require the electrical insulation.

  3. Electrochemical Corrosion Behavior of Spray-Formed Boron-Modified Supermartensitic Stainless Steel

    Science.gov (United States)

    Zepon, Guilherme; Nogueira, Ricardo P.; Kiminami, Claudio S.; Botta, Walter J.; Bolfarini, Claudemiro

    2017-01-01

    Spray-formed boron-modified supermartensitic stainless steel (SMSS) grades are alloys developed to withstand severe wear conditions. The addition of boron to the conventional chemical composition of SMSS, combined with the solidification features promoted by the spray forming process, leads to a microstructure composed of low carbon martensitic matrix reinforced by an eutectic network of M2B-type borides, which considerably increases the wear resistance of the stainless steel. Although the presence of borides in the microstructure has a very beneficial effect on the wear properties of the alloy, their effect on the corrosion resistance of the stainless steel was not comprehensively evaluated. The present work presents a study of the effect of boron addition on the corrosion resistance of the spray-formed boron-modified SMSS grades by means of electrochemical techniques. The borides fraction seems to have some influence on the repassivation kinetics of the spray-formed boron-modified SMSS. It was shown that the Cr content of the martensitic matrix is the microstructural feature deciding the corrosion resistance of this sort of alloys. Therefore, if the Cr content in the alloy is increased to around 14 wt pct to compensate for the boron consumed by the borides formation, the corrosion resistance of the alloy is kept at the same level of the alloy without boron addition.

  4. Synthesis of Boron Nanowires, Nanotubes, and Nanosheets

    Directory of Open Access Journals (Sweden)

    Rajen B. Patel

    2015-01-01

    Full Text Available The synthesis of boron nanowires, nanotubes, and nanosheets using a thermal vapor deposition process is reported. This work confirms previous research and provides a new method capable of synthesizing boron nanomaterials. The materials were made by using various combinations of MgB2, Mg(BH42, MCM-41, NiB, and Fe wire. Unlike previously reported methods, a nanoparticle catalyst and a silicate substrate are not required for synthesis. Two types of boron nanowires, boron nanotubes, and boron nanosheets were made. Their morphology and chemical composition were determined through the use of scanning electron microscopy, transmission electron microscopy, and electron energy loss spectroscopy. These boron-based materials have potential for electronic and hydrogen storage applications.

  5. Prediction of boron carbon nitrogen phase diagram

    Science.gov (United States)

    Yao, Sanxi; Zhang, Hantao; Widom, Michael

    We studied the phase diagram of boron, carbon and nitrogen, including the boron-carbon and boron-nitrogen binaries and the boron-carbon-nitrogen ternary. Based on the idea of electron counting and using a technique of mixing similar primitive cells, we constructed many ''electron precise'' structures. First principles calculation is performed on these structures, with either zero or high pressures. For the BN binary, our calculation confirms that a rhmobohedral phase can be stablized at high pressure, consistent with some experimental results. For the BCN ternary, a new ground state structure is discovered and an Ising-like phase transition is suggested. Moreover, we modeled BCN ternary phase diagram and show continuous solubility from boron carbide to the boron subnitride phase.

  6. Delivery of Liposomes with Different Sizes to Mice Brain after Sonication by Focused Ultrasound in the Presence of Microbubbles.

    Science.gov (United States)

    Shen, Yuanyuan; Guo, Jinxuan; Chen, Gaoshu; Chin, Chien Ting; Chen, Xin; Chen, Jian; Wang, Feng; Chen, Shiguo; Dan, Guo

    2016-07-01

    findings are expected to provide useful information for developing FUS with microbubbles as an effective trans-BBB liposomal drug delivery strategy.

  7. The comparison of protein-entrapped liposomes and lipoparticles: preparation, characterization, and efficacy of cellular uptake

    Directory of Open Access Journals (Sweden)

    Chang WK

    2011-10-01

    Full Text Available Wei-Kuo Chang1, Yu-Ju Tai2, Chiao-Hsi Chiang3, Chieh-Shen Hu2, Po-Da Hong2, Ming-Kung Yeh3,4 1Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taiwan, ROC; 2Graduate Institute of Engineering, National Taiwan University of Science and Technology, Taipei, Taiwan, ROC; 3School of Pharmacy, National Defense Medical Center, Taipei, Taiwan, ROC; 4Institute of Preventive Medicine, National Defense Medical Center, Sanhsia, Taipei, Taiwan, ROC Abstract: Fluorescein isothiocyanate-conjugated bovine serum albumin (FITC-BSA-loaded polyethylene glycol (PEG-modified liposomes and lipoparticles with high protein entrapment were developed. The lipid formula of the liposomes contained PEGylated lipids and unsaturated fatty acids for enhancing membrane fluidity and effective delivery into cells. The preparation techniques, lipid content, and PEG-modified lipoparticle ratios were evaluated. The PEG-modified lipoparticles prepared by ethanol injection extrusion (100 nm pore size achieve a population of blank liposomes with a mean size of 125 ± 2.3 nm and a zeta potential of —12.4 ± 1.5 mV. The average particle size of the PEG-modified lipoparticles was 133.7 ± 8.6 nm with a zeta potential of +13.3 mV. Lipoparticle conformation was determined using transmission electron microscopy and field-emission scanning electron microscopy. The FITC-BSA encapsulation efficiency was dramatically increased from 19.0% for liposomes to 59.7% for lipoparticles. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE results confirmed the preparation process, and an 8-hour leaching test did not harm the protein structure. Once prepared, the physical and chemical stability of the PEG-modified lipoparticle formulations was satisfactory over 90 days. In vitro retention tests indicated that the 50% retention time for the protein-containing lipoparticles was 7.9 hours, substantially longer than

  8. Liposomal nanoparticles as a drug delivery vehicle against osteosarcoma

    Science.gov (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

  9. Development of a Biomedical Micro/Nano Robot for Drug Delivery.

    Science.gov (United States)

    Zhang, Zhenhai; Li, Zhifei; Yu, Wei; Li, Kejie; Xie, Zhihong

    2015-04-01

    Flagellated bacteria have been utilized as potential swimming micro-robotic bodies for propulsion of spherical liposome by attaching several bacteria on their surface. Liposome as a drug delivery vehicle can contain biologically active compounds. In this work, the antibody binding technique is developed to attach bacteria to liposome's surface. Consequently, the stochastic effect of bacterial propulsion of liposome is investigated analytically and experimentally. It is shown that the mobility of liposome with bacteria was higher than that of liposome without bacteria. Experimental data matches well with statistical calculation.

  10. Preliminary Studies on X-Ray-sensitive Liposome

    Institute of Scientific and Technical Information of China (English)

    MENG Fan-xu; XU Hua-ping; QI Yan-fei; XU Kun; SONG Xiu-ling; NIU Shu; LI Juan

    2012-01-01

    The synthesis of a new type of X-ray-sensitive compound “di-(1-hydroxylundecyl)diselenide” and its application in the preparation of a new type of liposome with X-ray sensitivity was reported.This new liposome was synthesized to encapsulate doxorubicin hydrochloride(Dox),with its physical and chemical properties,stability,and radiation sensitivity determined.Based on the pH-gradient method,liposomal Dox was prepared via ultrasonic emulsification and then purified on a Sephadex G50 mini-column.UV spectrophotometry and liquid chromatography were used to detect the encapsulation efficiency and radiation sensitivity of the Dox-loaded liposome.The results show that through changes in release rate,this liposome shows a relative radiosensitivity.In terms of radiation sensitivity,the drug leak rate of the X-ray-sensitive Dox-loaded liposome increased gradually and peaked at 65.4% under the X-ray radiation of a dose of 10 Gy or more than 10 Gy,which is significantly different from that of ordinary liposomes.Meanwhile,X-ray-sensitive Dox-loaded liposome has a good dispersion stability,with an average particle size of approximate 120 nm.The efficiency of this liposome encapsulating Dox was 75.84%,slightly lower than that of ordinary liposomes.The X-ray-sensitive Dox-loaded liposome exhibited suspension stability within 30 d of storage at 4 ℃,without visible precipitation.Di-(1-hydroxylundecyl)diselenide is safe and noncytotoxic and compared with those of synthetic phospholipids its synthesis is low cost and does not require complex conditions.

  11. 用于 n/γ混合场测量的涂硼电离室研制%Development of Boron-lined Ionization Chamber Used in n/γ Mixed Field

    Institute of Scientific and Technical Information of China (English)

    朱立; 魏志勇; 陈国云; 雷升杰; 方美华; 贾文宝; 张紫霞; 府宇

    2013-01-01

    研制了一种能同时测量混合场中γ和中子注量率的涂硼电离室,并实验测试了其性能。涂硼电离室由两个大小和结构一致的腔室组成:1个仅对γ灵敏,另1个对γ与中子均灵敏。用强度为2.7×107 s-1的Am-Be源测得电离室的中子灵敏度达9.2×10-16 A/(cm-2· s-1),在剂量率为5.24μGy/h的137 Csγ场中,电离室的γ灵敏度达7.36×10-16 A/(MeV · cm -2· s-1)。涂硼电离室 I-V 曲线坪长为600 V ,坪斜小于4%/100 V ,在工作电压为-400 V时,其γ补偿修正系数<5%,可用于核设施周围的混合场监测。%A boron-lined ionization chamber used in n/γ mixed field with better performance was developed .The boron-lined ionization chamber consists of two cavity rooms with the same size:One is for γ ,the other is for both γ and neutron .The neutron sensitivity reaches a level of 9.2 × 10 -16 A/(cm -2 · s-1 ) with a calibrated Am-Be neutron source with neutron intensity estimated to be 2.7 × 107 s-1 , and the γsensitivity reaches a level of 7.36 × 10 -16 A/(MeV · cm -2 · s-1 ) with a calibrated 137 Cs source with 5.24 μGy/h dose rate .The plateau length is 600 V and the slope is less than 4% /100 V .An average γ compensation coefficient is less than 5% at work voltage of-400 V ,w hich can be used to monitor the n/γ mixed field around reactors .

  12. Efficient drug delivery to atherosclerotic lesions and the antiatherosclerotic effect by dexamethasone incorporated into liposomes in atherogenic mice.

    Science.gov (United States)

    Chono, Sumio; Tauchi, Yoshihiko; Deguchi, Yoshiharu; Morimoto, Kazuhiro

    2005-05-01

    In order to confirm the efficacy of dexamethasone (DXM) incorporated into liposomes (DXM-liposomes) on atherosclerosis, drug delivery to atherosclerotic lesions and the antiatherosclerotic effect by DXM-liposomes were investigated in atherogenic mice. DXM-liposomes were prepared with egg yolk phosphatidylcholine, cholesterol and dicetylphosphate in a lipid molar ratio of 7/2/1 by the hydration method and then adjusted to three different particle sizes to clarify the influence of particle size on the drug delivery to atherosclerotic lesions and the effect on atherosclerosis. The particle sizes of DXM-liposomes were 519 nm (L500), 202 nm (L200) and 68.6 nm (L70), respectively. In both size, DXM concentration and DXM/lipid molar ratio in DXM-liposomes suspension were 1 mg DXM/ml and 0.134 mol DXM/mol total lipids, respectively. Atherogenic mice used as an experimental model develop an atherosclerotic lesion in the aorta and they were prepared by feeding an atherogenic diet for 14 weeks. The aortic pharmacokinetics of DXM-liposomes was examined by intravenous administration to atherogenic mice. The aortic uptake clearance of DXM in atherogenic mice treated with L200 was 2.6--3.2 fold greater than that in animals treated with L500, L70 or free DXM (f-DXM). Furthermore, the effects of DXM-liposomes on atherosclerosis were examined by intravenous administration to atherogenic mice once a week from 8 to 14 weeks. The antiatherosclerotic effects of DXM-liposomes were evaluated by determination of the aortic cholesterol ester (CE) level. The aortic CE level in atherogenic mice treated with L200 (55 microg DXM/kg) was significantly lower than that in animals treated with PBS. The antiatherosclerotic effect of L200 (55 microg DXM/kg) was significantly more potent than that of f-DXM (550 microg DXM/kg). These findings suggest that efficient delivery of DXM to the atherosclerotic lesions by L200 induces an excellent antiatherosclerotic effect at a lower dose. Therefore, L200 may

  13. Composite Reinforcement using Boron Nitride Nanotubes

    Science.gov (United States)

    2014-05-09

    Final 3. DATES COVERED (From - To) 11-Mar-2013 to 10-Mar-2014 4. TITLE AND SUBTITLE Composite Reinforcement using Boron Nitride Nanotubes...AVAILABILITY STATEMENT Approved for public release. 13. SUPPLEMENTARY NOTES 14. ABSTRACT Boron nitride nanotubes have been proposed as a...and titanium (Ti) metal clusters with boron nitride nanotubes (BNNT). First-principles density-functional theory plus dispersion (DFT-D) calculations

  14. Oxygen radical functionalization of boron nitride nanosheets

    OpenAIRE

    MAY, PETER; Coleman, Jonathan; MCGOVERN, IGNATIUS; GOUNKO, IOURI; Satti, Amro

    2012-01-01

    PUBLISHED The covalent chemical functionalization of exfoliated hexagonal boron-nitride nanosheets (BNNSs) is achieved by the solution phase oxygen radical functionalization of boron atoms in the h-BN lattice. This involves a two-step procedure to initially covalently graft alkoxy groups to boron atoms and the subsequent hydrolytic defunctionalisation of the groups to yield hydroxyl-functionalized BNNSs (OH-BNNSs). Characterization of the functionalized-BNNSs using HR-TEM, Raman, UV-Vis, F...

  15. Peptide-22 and Cyclic RGD Functionalized Liposomes for Glioma Targeting Drug Delivery Overcoming BBB and BBTB.

    Science.gov (United States)

    Chen, Cuitian; Duan, Ziqing; Yuan, Yan; Li, Ruixiang; Pang, Liang; Liang, Jianming; Xu, Xinchun; Wang, Jianxin

    2017-02-22

    Chemotherapy outcomes for the treatment of glioma remain unsatisfied due to the inefficient drug transport across BBB/BBTB and poor drug accumulation in the tumor site. Nanocarriers functionalized with different targeting ligands are considered as one of the most promising alternatives. However, few studies were reported to compare the targeting efficiency of the ligands and develop nanoparticles to realize BBB/BBTB crossing and brain tumor targeting simultaneously. In this study, six peptide-based ligands (Angiopep-2, T7, Peptide-22, c(RGDfK), D-SP5 and Pep-1), widely used for brain delivery, were selected to decorate liposomes, respectively, so as to compare their targeting ability to BBB or BBTB. Based on the in vitro cellular uptake results on BCECs and HUVECs, Peptide-22 and c(RGDfK) were picked to construct a BBB/BBTB dual-crossing, glioma-targeting liposomal drug delivery system c(RGDfK)/Pep-22-DOX-LP. In vitro cellular uptake demonstrated that the synergetic effect of c(RGDfK) and Peptide-22 could significantly increase the internalization of liposomes on U87 cells. In vivo imaging further verified that c(RGDfK)/Pep-22-LP exhibited higher brain tumor distribution than single ligand modified liposomes. The median survival time of glioma-bearing mice treated with c(RGDfK)/Pep-22-DOX-LP (39.5 days) was significantly prolonged than those treated with free doxorubicin or other controls. In conclusion, the c(RGDfK) and Peptide-22 dual-modified liposome was constructed based on the targeting ability screening of various ligands. The system could effectively overcome BBB/BBTB barriers, target to tumor cells and inhibit the growth of glioma, which proved its potential for improving the efficacy of chemotherapeutics for glioma therapy.

  16. Predicted boron-carbide compounds: a first-principles study.

    Science.gov (United States)

    Wang, De Yu; Yan, Qian; Wang, Bing; Wang, Yuan Xu; Yang, Jueming; Yang, Gui

    2014-06-14

    By using developed particle swarm optimization algorithm on crystal structural prediction, we have explored the possible crystal structures of B-C system. Their structures, stability, elastic properties, electronic structure, and chemical bonding have been investigated by first-principles calculations with density functional theory. The results show that all the predicted structures are mechanically and dynamically stable. An analysis of calculated enthalpy with pressure indicates that increasing of boron content will increase the stability of boron carbides under low pressure. Moreover, the boron carbides with rich carbon content become more stable under high pressure. The negative formation energy of predicted B5C indicates its high stability. The density of states of B5C show that it is p-type semiconducting. The calculated theoretical Vickers hardnesses of B-C exceed 40 GPa except B4C, BC, and BC4, indicating they are potential superhard materials. An analysis of Debye temperature and electronic localization function provides further understanding chemical and physical properties of boron carbide.

  17. Boron deposition from fused salts. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Smith, M.L.

    1980-08-01

    A partial evaluation of the feasibility of a process to electrodeposit pure coherent coatings of elemental boron from molten fluorides has been performed. The deposit produced was powdery and acicular, unless the fluoride melt was purified to have very low oxygen concentration. When the oxygen activity was reduced in the melt by addition of crystalline elemental boron, dense, amorphous boron deposit was produced. The boron deposits produced had cracks but were otherwise pure and dense and ranged up to 0.35 mm thick. Information derived during this project suggests that similar deposits might be obtained crack-free up to 1.00 mm thick by process modifications and improvements.

  18. Mineral resource of the month: boron

    Science.gov (United States)

    Crangle, Robert D.

    2012-01-01

    The article offers information on the mineral, boron. Boron compounds, particularly borates, have more commercial applications than its elemental relative which is a metalloid. Making up the 90% of the borates that are used worldwide are colemanite, kernite, tincal, and ulexite. The main borate deposits are located in the Mojave Desert of the U.S., the Tethyan belt in southern Asia, and the Andean belt of South America. Underground and surface mining are being used in gathering boron compounds. INSETS: Fun facts;Boron production and consumption.

  19. Boron removal from geothermal waters by electrocoagulation

    Energy Technology Data Exchange (ETDEWEB)

    Yilmaz, A. Erdem [Atatuerk University, Faculty of Engineering, Department of Environmental Engineering., 25240 Erzurum (Turkey)], E-mail: aerdemy@atauni.edu.tr; Boncukcuoglu, Recep [Atatuerk University, Faculty of Engineering, Department of Environmental Engineering., 25240 Erzurum (Turkey); Kocakerim, M. Muhtar [Atatuerk University, Faculty of Engineering, Department of Chemical Engineering, 25240 Erzurum (Turkey); Yilmaz, M. Tolga; Paluluoglu, Cihan [Atatuerk University, Faculty of Engineering, Department of Environmental Engineering., 25240 Erzurum (Turkey)

    2008-05-01

    Most of the geothermal waters in Turkey contain extremely high concentration of boron when they are used for irrigation. The use of geothermal waters for irrigation can results in excess amount deposition of boron in soil. On the other hand, a minimal boron concentration is required for irrigational waters. In this study, electrocoagulation (EC) was selected as a treatment process for the removal of boron from thermal waters obtained from Ilica-Erzurum in Turkey. Current density (CD), pH of solution and temperature of solution were selected as operational parameters. The results showed that boron removal efficiency increased from pH 4.0 to 8.0 and decreased at pH 10.0. Although boron removal efficiency was highest at pH 8.0, energy consumption was very high at this pH value compared to other pH intervals. Boron removal efficiency reached to 95% with increasing current density from 1.5 to 6.0 mA/cm{sup 2}, but energy consumption was also increased in this interval. At higher temperatures of solution, such as 313 and 333 K, boron removal efficiency increased. At optimum conditions, boron removal efficiency in geothermal water reached up to 95%.

  20. Conduction mechanism in boron carbide

    Science.gov (United States)

    Wood, C.; Emin, D.

    1984-01-01

    Electrical conductivity, Seebeck-coefficient, and Hall-effect measurements have been made on single-phase boron carbides, B(1-x)C(x), in the compositional range from 0.1 to 0.2 X, and between room temperature and 1273 K. The results indicate that the predominant conduction mechanism is small-polaron hopping between carbon atoms at geometrically inequivalent sites.

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

    Science.gov (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

    2013-02-01

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

  2. New approaches in the management of advanced breast cancer – role of combination treatment with liposomal doxorubicin

    Directory of Open Access Journals (Sweden)

    Iain RJ Macpherson

    2009-08-01

    Full Text Available Iain RJ Macpherson, TR Jeffry EvansBeatson West of Scotland Cancer Centre, Glasgow, United KingdomAbstract: Metastatic breast cancer (MBC remains a major cause of morbidity and mortality in women worldwide. For three decades doxorubicin, alone or in combination with other cytotoxic agents, has been a mainstay of systemic therapy for MBC. However, its use is limited by cumulative cardiotoxicity. More recently liposomal formulations of doxorubicin have been developed which exhibit equal efficacy but reduced cardiotoxicity in comparison to conventional doxorubicin. The novel toxicity profile of liposomal doxorubicins has prompted their evaluation with various cytotoxic agents in patients with MBC. In addition, their favorable cardiac safety profile has prompted re-evaluation of concomitant therapy with doxorubicin and trastuzumab, a regimen of proven efficacy in MBC but previously considered to be associated with significant cardiotoxicity. We review clinical trial data addressing combination therapy with both pegylated and non-pegylated liposomal doxorubicin in patients with MBC.Keywords: breast cancer, anthracycline, liposome-encapsulated doxorubicin, pegylated liposomal doxorubicin, cardiotoxicity

  3. Characterization and release studies of liposomal gels containing glutathione/cyclodextrins complexes potentially useful for cutaneous administration.

    Science.gov (United States)

    Cutrignelli, Annalisa; Lopedota, Angela; Denora, Nunzio; Laquintana, Valentino; Tongiani, Serena; Franco, Massimo

    2014-04-01

    The aim of this work is to develop and characterize a formulation intended for the cutaneous administration of glutathione (γ-glutamylcysteinylglycine, GSH), potentially useful for cellular defense against UV-induced damage. For this purpose, liposomes containing GSH or GSH/cyclodextrins(CDs) inclusion complexes as well as liposomes dispersed within a hydrophilic gel, were evaluated. These formulations were designed in order to obtain a system combining the advantages of liposomes as vehicles for topical drug delivery with those of CDs as penetration enhancers. The studied CDs were the natural (β-CD) and chemically modified (i.e., HP-β-CD and CH3 -β-CD) cyclodextrins. The prepared liposomes showed homogeneous size distribution, mean diameter in the range 622-1435 nm, small positive charge (+3.1 to +6.6 mV), and encapsulation efficiency of the peptide in the range 13.6%-23.7%. Release studies showed that the presence of the oligosaccharide may influence to some extent the amount of drug released, whereas stability studies clearly point out that the incorporation in a hydrophilic gel of 2-hydroxyethylcellulose insures a stable formulation maintaining unchanged the characteristics of liposomal vesicles.

  4. Micro-total analysis system for virus detection: microfluidic pre-concentration coupled to liposome-based detection.

    Science.gov (United States)

    Connelly, John T; Kondapalli, Sowmya; Skoupi, Marc; Parker, John S L; Kirby, Brian J; Baeumner, Antje J

    2012-01-01

    An integrated microfluidic biosensor is presented that combines sample pre-concentration and liposome-based signal amplification for the detection of enteric viruses present in environmental water samples. This microfluidic approach overcomes the challenges of long assay times of cell culture-based methods and the need to extensively process water samples to eliminate inhibitors for PCR-based methods. Here, viruses are detected using an immunoassay sandwich approach with the reporting antibodies tagged to liposomes. Described is the development of the integrated device for the detection of environmentally relevant viruses using feline calicivirus (FCV) as a model organism for human norovirus. In situ fabricated nanoporous membranes in glass microchannels were used in conjunction with electric fields to achieve pre-concentration of virus-liposome complexes and therefore enhance the antibody-virus binding efficiency. The concentrated complexes were eluted to a detection region downstream where captured liposomes were lysed to release fluorescent dye molecules that were then quantified using image processing. This system was compared to an optimized electrochemical liposome-based microfluidic biosensor without pre-concentration. The limit of detection of FCV of the integrated device was at 1.6 × 10(5) PFU/mL, an order of magnitude lower than that obtained using the microfluidic biosensor without pre-concentration. This significant improvement is a key step toward the goal of using this integrated device as an early screening system for viruses in environmental water samples.

  5. Pharmaceutical development and preclinical evaluation of a GMP-grade anti-inflammatory nanotherapy

    NARCIS (Netherlands)

    Lobatto, Mark E.; Calcagno, Claudia; Otten, Maarten J.; Millon, Antoine; Ramachandran, Sarayu; Paridaans, Maarten P M; van der Valk, Fleur M.; Storm, G; Stroes, Erik S G; Fayad, Zahi A.; Mulder, Willem J M; Metselaar, Josbert M.

    2015-01-01

    The present study describes the development of a good manufacturing practice (GMP)-grade liposomal nanotherapy containing prednisolone phosphate for the treatment of inflammatory diseases. After formulation design, GMP production was commenced which yielded consistent, stable liposomes sized 100. nm

  6. Pharmaceutical development and preclinical evaluation of a GMP-grade anti-inflammatory nanotherapy

    NARCIS (Netherlands)

    Lobatto, Mark E.; Calcagno, Claudia; Otten, Maarten J.; Millon, Antoine; Ramachandran, Sarayu; Paridaans, Maarten P.M.; Valk, van der Fleur M.; Storm, Gert; Stroes, Erik S.G.; Fayad, Zahi A.; Mulder, Willem J.M.; Metselaar, Josbert M.

    2015-01-01

    The present study describes the development of a good manufacturing practice (GMP)-grade liposomal nanotherapy containing prednisolone phosphate for the treatment of inflammatory diseases. After formulation design, GMP production was commenced which yielded consistent, stable liposomes sized 100 nm

  7. Effects of Boron Nutrition on 45Ca Retranslocation and Distribution in Rape (Brassica napus L. ) Cultivars

    Institute of Scientific and Technical Information of China (English)

    WANG Huo-yan; WANG Yun-hua; WU Li-shu; DU Chang-wen; XU Fang-sun

    2003-01-01

    Using tracer techniques with the radioisotope 45Ca, the effects of boron supply from soil andnutrient solution on the retranslocation of 45 Ca from leaves to other parts of rape plants were studied. Resultsindicated that only a small portion of foliar-applied 45Ca could be retranslocated to other parts of the rapeplant. There was no pronounced effect of boron level in the soil on 45 Ca retranslocation. Increasing boron con-centrations in the nutrient solution significantly reduced 45 Ca radioactivity in root and stem, but increased 45 Cauptake and 45 Ca translocation to the upper leaves of rape plants. It was suggested that 45 Ca absorbed by newlydeveloped roots was easily distributed to upper leaves of rape plants. Boron may alter distribution of calciumvia its effect on root development or growth of newly developed roots.

  8. Polyelectrolyte stabilized multilayered liposomes for oral delivery of paclitaxel

    DEFF Research Database (Denmark)

    Jain, Sanyog; Kumar, Dinesh; Swarnakar, Nitin K;

    2012-01-01

    Paclitaxel (PTX) loaded layersome formulations were prepared using layer-by-layer assembly of the polyelectrolytes over liposomes. Stearyl amine was utilized to provide positive charge to the liposomes, which were subsequently coated with anionic polymer polyacrylic acid (PAA) followed by coating...

  9. Immunological Effect of Subunit Influenza Vaccine Entrapped by Liposomes

    Institute of Scientific and Technical Information of China (English)

    SHUI-HUA ZHANG; JIA-XU LIANG; SHU-YAN DAI; XIAO-LIN QIU; YAN-RONG YI; YUN PAN

    2009-01-01

    Objective To elevate the immunological effect of subunit influenza vaccine in infants and aged people (over 60) using liposomal adjuvant in the context of its relatively low immunity and to investigate the relation between vaccine antigens and liposomal characteristics. Methods Several formulations of liposomal subunit influenza vaccine were prepared. Their relevant characteristics were investigated to optimize the preparation method. Antisera obtained from immunizinged mice were used to evaluate the antibody titers of various samples by HI and ELISA. Results Liposomal trivalent influenza vaccine prepared by film evaporation in combinedation with freeze-drying significantly increased its immunological effect in SPF Balb/c mice. Liposomal vaccine stimulated the antibody titer of H3N2, H1N1, and B much stronger than conventional influenza vaccine. As a result, liposomal vaccine (mean size: 4.5-5.5 μm, entrapment efficiency: 30%-40%) significantly increased the immunological effect of subunit influenza vaccine. Conclusion The immune effect of liposomal vaccine depends on different antigens, and enhanced immunity is not positively correlated with the mean size of liposome or its entrapped efficiency.

  10. Biophysical characterization of gold nanoparticles-loaded liposomes.

    Science.gov (United States)

    Mady, Mohsen Mahmoud; Fathy, Mohamed Mahmoud; Youssef, Tareq; Khalil, Wafaa Mohamed

    2012-10-01

    Gold nanoparticles were prepared and loaded into the bilayer of dipalmitoylphosphatidylcholine (DPPC) liposomes, named as gold-loaded liposomes. Biophysical characterization of gold-loaded liposomes was studied by transmission electron microscopy (TEM) and Fourier transform infrared (FTIR) spectroscopy as well as turbidity and rheological measurements. FTIR measurements showed that gold nanoparticles made significant changes in the frequency of the CH(2) stretching bands, revealing that gold nanoparticles increased the number of gauche conformers and create a conformational change within the acyl chains of phospholipids. The transmission electron micrographs (TEM) revealed that gold nanoparticles were loaded in the liposomal bilayer. The zeta potential of DPPC liposomes had a more negative value after incorporating of Au NPs into liposomal membranes. Turbidity studies revealed that the loading of gold nanoparticles into DPPC liposomes results in shifting the temperature of the main phase transition to a lower value. The membrane fluidity of DPPC bilayer was increased by loading the gold nanoparticles as shown from rheological measurements. Knowledge gained in this study may open the door to pursuing liposomes as a viable strategy for Au NPs delivery in many diagnostic and therapeutic applications.

  11. Biodistribution of liposome-entrapped human gamma-globulin.

    Science.gov (United States)

    García-Santana, María A; Duconge, Jorge; Sarmiento, María E; Lanio-Ruíz, María E; Becquer, María A; Izquierdo, Luís; Acosta-Domínguez, Armando

    2006-09-01

    The present study was aimed at the preparation and performance evaluation of Intacglobin-loaded liposomes for selective drug presentation to the lungs. Egg phosphatidylcholine- and cholesterol-based liposomes (1:1 and 1:0.25 mol/mol) were prepared by a dehydration-rehydration procedure. A tissue distribution study after single intranasal administration of 0.5 microCi 125I-Intacglobin-loaded liposomes was conducted in Balb/c mice. The efficiencies of drug entrapment (30%) and the average diameters did not differ significantly between the two liposome formulations. However, liposomes composed of an increased cholesterol amount showed a lower in vitro drug release rate. The airway penetration efficiency of the liposomal formulation was determined by the cumulative percentage of the dose reaching the lungs (AUC) and its sojourn time therein, and were 1.7- and 2.2-times higher compared with the plain 125I- Intacglobin solution-based formulation, respectively. A significantly greater (p<0.001) drug localization index after 24 h was found at the lungs in comparison with the other tissues (p<0.01), although similar values were detected between groups following administration of either liposomes or control solutions, despite the formulations attributes. In conclusion, it is suggested that longer Intacglobin exposure at the pulmonary region is observed after administration of the liposomal formulation. The results open future perspectives in assessing local passive immunization for the treatment of respiratory infectious diseases.

  12. Boron neutron capture therapy of brain tumors: an emerging therapeutic modality.

    Science.gov (United States)

    Barth, R F; Soloway, A H; Goodman, J H; Gahbauer, R A; Gupta, N; Blue, T E; Yang, W; Tjarks, W

    1999-03-01

    Boron neutron capture therapy (BNCT) is based on the nuclear reaction that occurs when boron-10, a stable isotope, is irradiated with low-energy thermal neutrons to yield alpha particles and recoiling lithium-7 nuclei. For BNCT to be successful, a large number of 10B atoms must be localized on or preferably within neoplastic cells, and a sufficient number of thermal neutrons must be absorbed by the 10B atoms to sustain a lethal 10B (n, alpha) lithium-7 reaction. There is a growing interest in using BNCT in combination with surgery to treat patients with high-grade gliomas and possibly metastatic brain tumors. The present review covers the biological and radiobiological considerations on which BNCT is based, boron-containing low- and high-molecular weight delivery agents, neutron sources, clinical studies, and future areas of research. Two boron compounds currently are being used clinically, sodium borocaptate and boronophenylalanine, and a number of new delivery agents are under investigation, including boronated porphyrins, nucleosides, amino acids, polyamines, monoclonal and bispecific antibodies, liposomes, and epidermal growth factor. These are discussed, as is optimization of their delivery. Nuclear reactors currently are the only source of neutrons for BNCT, and the fission reaction within the core produces a mixture of lower energy thermal and epithermal neutrons, fast or high-energy neutrons, and gamma-rays. Although thermal neutron beams have been used clinically in Japan to treat patients with brain tumors and cutaneous melanomas, epithermal neutron beams now are being used in the United States and Europe because of their superior tissue-penetrating properties. Currently, there are clinical trials in progress in the United States, Europe, and Japan using a combination of debulking surgery and then BNCT to treat patients with glioblastomas. The American and European studies are Phase I trials using boronophenylalanine and sodium borocaptate, respectively

  13. Boron coating on boron nitride coated nuclear fuels by chemical vapor deposition

    Science.gov (United States)

    Durmazuçar, Hasan H.; Gündüz, Güngör

    2000-12-01

    Uranium dioxide-only and uranium dioxide-gadolinium oxide (5% and 10%) ceramic nuclear fuel pellets which were already coated with boron nitride were coated with thin boron layer by chemical vapor deposition to increase the burn-up efficiency of the fuel during reactor operation. Coating was accomplished from the reaction of boron trichloride with hydrogen at 1250 K in a tube furnace, and then sintering at 1400 and 1525 K. The deposited boron was identified by infrared spectrum. The morphology of the coating was studied by using scanning electron microscope. The plate, grainy and string (fiber)-like boron structures were observed.

  14. Stereocontrolled synthesis of 1,5-stereogenic centers through three-carbon homologation of boronic esters.

    Science.gov (United States)

    Unsworth, Phillip J; Leonori, Daniele; Aggarwal, Varinder K

    2014-09-08

    Allylic pinacol boronic esters are stable toward 1,3-borotropic rearrangement. We developed a Pd(II)-mediated isomerization process that gives di- or trisubstituted allylic boronic esters with high E selectivity. The combination of this method with lithiation