Science.gov

Sample records for potential delivery agent

  1. Double layered hydroxides as potential anti-cancer drug delivery agents.

    PubMed

    Riaz, Ufana; Ashraf, S M

    2013-04-01

    The emergence of nanotechnology has changed the scenario of the medical world by revolutionizing the diagnosis, monitoring and treatment of cancer. This nanotechnology has been proved miraculous in detecting cancer cells, delivering chemotherapeutic agents and monitoring treatment from non-specific to highly targeted killing of tumor cells. In the past few decades, a number of inorganic materials have been investigated such as calcium phosphate, gold, carbon materials, silicon oxide, iron oxide, and layered double hydroxide (LDH) for examining their efficacy in targeting drug delivery. The reason behind the selection of these inorganic materials was their versatile and unique features efficient in drug delivery, such as wide availability, rich surface functionality, good biocompatibility, potential for target delivery, and controlled release of the drug from these inorganic nanomaterials. Although, the drug-LDH hybrids are found to be quite instrumental because of their application as advanced anti-cancer drug delivery systems, there has not been much research on them. This mini review is set to highlight the advancement made in the use of layered double hydroxides (LDHs) as anti-cancer drug delivery agents. Along with the advantages of LDHs as anti-cancer drug delivery agents, the process of interaction of some of the common anti-cancer drugs with LDH has also been discussed.

  2. Mechanistic study of IR-780 dye as a potential tumor targeting and drug delivery agent.

    PubMed

    Zhang, Erlong; Luo, Shenglin; Tan, Xu; Shi, Chunmeng

    2014-01-01

    IR-780 iodide, a near-infrared fluorescent heptamethine dye, has been recently characterized to exhibit preferential accumulation property in the mitochondria of tumor cells. In this study, we investigated the possible mechanisms for its tumor selective activity and its potential as a drug delivery carrier. Results showed that the energy-dependent uptake of IR-780 iodide into the mitochondria of tumor cells was affected by glycolysis and plasma membrane potential. Moreover, OATP1B3 subtype of organic anion transporter peptides (OATPs) may play a dominant role in the transportation of IR-780 iodide into tumor cells, while cellular endocytosis, mitochondrial membrane potential and the ATP-binding cassette transporters did not show significant influence to its accumulation. We further evaluated the potential of IR-780 iodide as a drug delivery carrier by covalent conjugation of IR-780 with nitrogen mustard (IR-780NM). In vivo imaging showed that IR-780NM remained the tumor targeting property, indicating that IR-780 iodide could be potentially applied as a drug delivery agent for cancer targeted imaging and therapy.

  3. Evaluation of boronated EGF as a potential delivery agent for BNCT of brain tumors

    SciTech Connect

    Yang, Weilian; Barth, R.F.; Adams, D.M.

    1996-12-31

    The epidermal growth factor receptor (EGFR) gene is often amplified in human glioblastomas, but, reflecting the cellular heterogeneity of these tumors, the frequency of amplification is variable. Since the number of EGFR has been considered as a potential target for the specific delivery of diagnostic and therapeutic agents to brain tumors. Initially, the focus was on using anti-EGFR monoclonal antibodies or their fragments, but within the past few years there has been increasing interest in using EGF based bioconjugates as targeting agents. Recently, we have described a method for the boronation of EGF and have characterized the resulting bioconjugates in vitro. In the present study, we have investigated the potential usefulness of boronated EGF as a delivery agent for neutron capture therapy in rats bearing intracerebral implants of the C6 glioma, which has been transfected with the gene encoding EGFR. Our results indicate that following intratumoral injection, boronated EGF selectivity targeted the transfected EGFR positive C6 glioma, and that the amount of delivered to the tumor exceeded by 3-4 orders of magnitude that which could be delivered by intravenous injection.

  4. Epidermal growth factor (EGF) as a potential targeting agent for delivery of boron to malignant gliomas

    SciTech Connect

    Capala, J.; Barth, R.F.; Adams, D.M.; Bailey, M.Q.; Soloway, A.H.; Carlsson, J.

    1994-12-31

    The majority of high grade gliomas express an amplified epidermal growth factor receptor (EGFR) gene, and this often is associated with an increase in cell surface receptor expression. The rapid internalization and degradation of EGF-EGFR complexes, as well as their high affinity make EGF a potential targeting agent for delivery of {sup 10}B to tumor cells with an amplified number of EGFR. Human glioma cells can expresses as many as 10{sup 5} {minus}10{sup 6} EGF receptors per cell, and if these could be saturated with boronated EGF, then > 10{sup 8} boron atoms would be delivered per cell. Since EGF has a comparatively low molecular weight ({approximately} 6 kD), this has allowed us to construct relatively small bioconjugates containing {approximately} 900 boron atoms per EGF molecule{sup 3}, which also had high affinity for EGFR on tumor cells. In the present study, the feasibility of using EGF receptors as a potential target for therapy of gliomas was investigated by in vivo scintigraphic studies using {sup 131}I{minus} or {sup 99m}{Tc}-labeled EGF in a rat brain tumor model. Our results indicate that intratumorally delivered boron- EGF conjugates might be useful for targeting EGFR on glioma cells if the boron containing moiety of the conjugates persisted intracellularly. Further studies are required, however, to determine if this approach can be used for BNCT of the rat glioma.

  5. Boron-containing folate receptor-targeted liposomes as potential delivery agents for neutron capture therapy.

    PubMed

    Pan, Xing Q; Wang, Huaqing; Shukla, Supriya; Sekido, Masaru; Adams, Dianne M; Tjarks, Werner; Barth, Rolf F; Lee, Robert J

    2002-01-01

    Boron neutron capture therapy (BNCT) depends on the selective delivery of a sufficient number of (10)B atoms to tumor cells to sustain a lethal (10)B(n,alpha)(7)Li reaction. Expression of FR frequently is amplified among human tumors. The goal of the present study was to investigate folate receptor (FR)-targeted liposomes as potential carriers for a series of boron-containing agents. Two highly ionized boron compounds, Na(2)[B(12)H(11)SH] and Na(3) (B(20)H(17)NH(3)), were incorporated into liposomes by passive loading with encapsulation efficiencies of 6% and 15%, respectively. In addition, five weakly basic boronated polyamines were investigated. Two were the spermidine derivatives: N(5)-(4-carboranylbutyl)spermidine.3HCl (SPD-5), N(5)-[4-(2-aminoethyl-o-carboranyl)butyl]spermidine.4HCl (ASPD-5). Three were the spermine derivatives: N(5)-(4-carboranylbutyl)spermine.4HCl (SPM-5), N(5)-[4-(2-aminoethyl-o-carboranyl)butyl]spermine.5HCl (ASPM-5), and N(5),N(10)-bis(4-carboranylbutyl)spermine.4 HCl (SPM-5,10). These were incorporated into liposomes by a pH-gradient-driven remote-loading method with varying loading efficiencies, which were influenced by the specific trapping agent and the structure of the boron compound. Greater loading efficiencies were obtained with lower molecular weight boron derivatives, using ammonium sulfate as the trapping agent, compared to those obtained with sodium citrate. The in vitro uptake of folate-derivatized, boronated liposomes was investigated using human KB squamous epithelial cancer cells, which have amplified FR expression. Higher cellular boron uptake (up to 1584 microg per 10(9) cells) was observed with FR-targeted liposomes than with nontargeted control liposomes (up to 154 microg per 10(9) cells), irrespective of the chemical form of the boron and the method used for liposomal preparation. KB cell binding of the FR-targeted liposomes was saturable and could be blocked by 1 mM free folic acid. Our findings suggest that further

  6. Evaluation of Degradation Properties of Polyglycolide and Its Potential as Delivery Vehicle for Anticancer Agents

    SciTech Connect

    Noorsal, K.; Ghani, S. M.; Yunos, D. M.; Mohamed, M. S. W.; Yahya, A. F.

    2010-03-11

    Biodegradable polymers offer a unique combination of properties that can be tailored to suit nearly any controlled drug delivery application. The most common biodegradable polymers used for biomedical applications are semicrystalline polyesters and polyethers which possess good mechanical properties and have been used in many controlled release applications. Drug release from these polymers may be controlled by several mechanisms and these include diffusion of drug through a matrix, dissolution of polymer matrix and degradation of the polymer. This study aims to investigate the degradation and drug release properties of polyglycolide (1.03 dL/g), in which, cis platin, an anticancer agent was used as the model drug. The degradation behaviour of the chosen polymer is thought to largely govern the release of the anticancer agent in vitro.

  7. The potential of PEGylated BaMnO3 nanoparticles as drug delivery agents

    NASA Astrophysics Data System (ADS)

    Hayat, Khizar; Khurshid, A.; Rafiq, M. A.; Durrani, S. K.; Zaidi, S. S. Z.; Ikram, M.; Hasan, M. M.

    2013-02-01

    Nanoparticles are extensively used as efficient drug carriers in various biological studies. PEGylated barium manganate powder consisting of nanoparticles was synthesized using a hydrothermal technique. The nanoparticle morphology of the powder was confirmed via scanning electron microscopy. The average diameter of the nanoparticles was ˜90 nm. The x-ray diffraction pattern revealed that these nanoparticles consisted of single phase polycrystalline 2H-BaMnO3. The PEGylated BaMnO3 nanoparticles were loaded with 5-aminolevulinic acid (5-ALA) to evaluate their drug carrying potential. The toxicity of these nanoparticles was tested against the Hep2c cell line and found to be suitable for biological applications. It was seen that the drug uptake was a million times higher in the case of encapsulation compared to a conventional drug delivery system. This new formulation may find extensive use in nanomedicine as a multidrug delivery system.

  8. Boronated Unnatural Cyclic Amino Acids as Potential Delivery Agents for Neutron Capture Therapy

    PubMed Central

    Kabalka, George W.; Shaikh, Aarif L.; Barth, Rolf F.; Huo, Tianyao; Yang, Weilian; Gordnier, Pamela M.; Chandra, Subhash

    2011-01-01

    Boron delivery characteristics of cis and trans isomers of a boronated unnatural amino acid, 1-amino-3-boronocyclopentanecarboxylic acid (ABCPC) were tested in B16 mouse model for human melanoma. Both ABCPC isomers delivered comparable boron to B16 melanoma tumor cells as L-p-boronophenylalanine (BPA). Secondary ion mass spectrometry (SIMS) analysis revealed the presence of boron throughout the tumor from these compounds, and a near homogeneous distribution between the nucleus and cytoplasm of B16 cells grown in vitro. These encouraging observations support further studies of these new boron carriers in BNCT. PMID:21481596

  9. Transdermal delivery of therapeutic agent

    NASA Technical Reports Server (NTRS)

    Kwiatkowski, Krzysztof C. (Inventor); Hayes, Ryan T. (Inventor); Magnuson, James W. (Inventor); Giletto, Anthony (Inventor)

    2008-01-01

    A device for the transdermal delivery of a therapeutic agent to a biological subject that includes a first electrode comprising a first array of electrically conductive microprojections for providing electrical communication through a skin portion of the subject to a second electrode comprising a second array of electrically conductive microprojections. Additionally, a reservoir for holding the therapeutic agent surrounding the first electrode and a pulse generator for providing an exponential decay pulse between the first and second electrodes may be provided. A method includes the steps of piercing a stratum corneum layer of skin with two arrays of conductive microprojections, encapsulating the therapeutic agent into biocompatible charged carriers, surrounding the conductive microprojections with the therapeutic agent, generating an exponential decay pulse between the two arrays of conductive microprojections to create a non-uniform electrical field and electrokinetically driving the therapeutic agent through the stratum corneum layer of skin.

  10. Evaluation of kappa carrageenan as potential carrier for floating drug delivery system: Effect of pore forming agents.

    PubMed

    Selvakumaran, Suguna; Muhamad, Ida Idayu; Abd Razak, Saiful Izwan

    2016-01-01

    Floating hydrogels were prepared from kappa carrageenan containing CaCO3 and NaHCO3 as pore forming agents. The effects of CaCO3 and NaHCO3 on hydrogel characterizations were investigated and compared. Amoxicillin trihydrate was used as a model drug. Characterizations of the hydrogels were carried out using Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and field emission scanning electron microscope (FESEM). As pore forming agents concentration increases, the porosity (%) and floating properties increased. NaHCO3 incorporated hydrogels showed higher porosity with shorter floating lag time (FLT) than CaCO3. Hydrogel which contained CaCO3 exhibited better gel stability over the control and NaHCO3 containing gel. Incorporation of CaCO3 into kappa carrageenan hydrogel showed smoother surface gels compared to those produced with NaHCO3. CaCO3 also showed higher drug entrapment efficiency and sustained drug release profile than NaHCO3. The results of these studies showed that, CaCO3 is an effective pore forming agents in κC hydrogels preparation as compare to NaHCO3. Thus, CaCO3 can be an excellent pore forming agent for an effective floating drug delivery system. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Cellular influx, efflux, and anabolism of 3-carboranyl thymidine analogs: potential boron delivery agents for neutron capture therapy.

    PubMed

    Sjuvarsson, Elena; Damaraju, Vijaya L; Mowles, Delores; Sawyer, Michael B; Tiwari, Rohit; Agarwal, Hitesh K; Khalil, Ahmed; Hasabelnaby, Sherifa; Goudah, Ayman; Nakkula, Robin J; Barth, Rolf F; Cass, Carol E; Eriksson, Staffan; Tjarks, Werner

    2013-11-01

    3-[5-{2-(2,3-Dihydroxyprop-1-yl)-o-carboran-1-yl}pentan-1-yl]thymidine (N5-2OH) is a first generation 3-carboranyl thymidine analog (3CTA) that has been intensively studied as a boron-10 ((10)B) delivery agent for neutron capture therapy (NCT). N5-2OH is an excellent substrate of thymidine kinase 1 and its favorable biodistribution profile in rodents led to successful preclinical NCT of rats bearing intracerebral RG2 glioma. The present study explored cellular influx and efflux mechanisms of N5-2OH, as well as its intracellular anabolism beyond the monophosphate level. N5-2OH entered cultured human CCRF-CEM cells via passive diffusion, whereas the multidrug resistance-associated protein 4 appeared to be a major mediator of N5-2OH monophosphate efflux. N5-2OH was effectively monophosphorylated in cultured murine L929 [thymidine kinase 1 (TK1(+))] cells whereas formation of N5-2OH monophosphate was markedly lower in L929 (TK1(-)) cell variants. Further metabolism to the di- and triphosphate forms was not observed in any of the cell lines. Regardless of monophosphorylation, parental N5-2OH was the major intracellular component in both TK1(+) and TK1(-) cells. Phosphate transfer experiments with enzyme preparations showed that N5-2OH monophosphate, as well as the monophosphate of a second 3-carboranyl thymidine analog [3-[5-(o-carboran-1-yl)pentan-1-yl]thymidine (N5)], were not substrates of thymidine monophosphate kinase. Surprisingly, N5-diphosphate was phosphorylated by nucleoside diphosphate kinase although N5-triphosphate apparently was not a substrate of DNA polymerase. Our results provide valuable information on the cellular metabolism and pharmacokinetic profile of 3-carboranyl thymidine analogs.

  12. Fabrication of triblock ABA type peptide dendrimer based on glutamic acid dimethyl ester and PEG as a potential nano drug delivery agent

    PubMed Central

    Namazi, Hassan; Toomari, Yousef; Abbaspour, Hassan

    2014-01-01

    Introduction: Peptide dendrimers build up from amino acids and they simulate to artificial proteins with globular architecture. These characteristics furnish peptide dendrimers with best biodegradability and biocompatibility in drug delivery systems. Methods: A barbell-like dendrimer from glutamic acid dimethyl ester-poly (ethylene glycol)-glutamic acid dimethyl ester as ABA-type triblock copolymer (PG-PEG-PG) was prepared with liquid-phase peptide synthesis via a divergent approach. PEG 600 diacid (PEG-A) and glutamic acid dimethyl ester were used as the core and the monomeric building blocks, respectively. Linear-dendritic copolymer was prepared in the presence of DCC in pyridine. Transmission electron microscope (TEM) was used for measuring the size of first generation (G1-COOH) and second generation (G2-COOH) of dendrimer compounds. Thermal behavior of the synthesized dendrimers was investigated using DSC. Results: The desired generations G1-COOH, G2-COOH and G3-COOH were prepared by divergent method using PEG diacid 600 as a core compound. The size range of the resulted particles was found to be 20-100 nm for various generations. The isolated dendrimer was examined as the drug-delivery agent and the controlled release was carried out for drug molecule in pH 7.4. Conclusion: Based on the obtained results, the synthesized biocompatible dendrimers could potentially be utilized as a drug carrier agent. PMID:25671173

  13. Strategies for the design and synthesis of boronated nucleic acid and protein components as potential delivery agents for neutron capture therapy

    SciTech Connect

    Wyzlic, I.M.; Tjarks, W.; Soloway, A.H.; Anisuzzaman, A.K.M.; Rong, Feng-Guang; Barth, R.F. )

    1994-03-30

    Strategies for the design and synthesis of boronated nucleosides, amino acids, and peptides as potential delivery agents for boron neutron capture therapy (BNCT) are described. For BNCT to be a useful treatment modality, there is a need to design and synthesize nontoxic boron compounds that selectively target tumor cells, accumulate in sufficient amounts (20-30 [mu]g [sup 10]B/g of tumor) and persist at therapeutic levels for a sufficient time prior to neutron irradiation. Boronated nucleosides, amino acids and peptides are such promising target compounds. Such structures may be selectively used by proliferating neoplastic cells compared with mitotically less active normal cells and therefore achieve the tissue differentials necessary for BNCT. The rationale for synthesis of boronated nucleic acid and protein components is discussed. Results of biological and clinical studies of some boronated nucleosides, nucleotides, amino acids and peptides are presented. Boronated nucleosides, amino acids and peptides can be considered as potential targeting agents for BNCT. 96 refs., 4 figs.

  14. Theranostic agents for intracellular gene delivery with spatiotemporal imaging

    PubMed Central

    Knipe, Jennifer M.; Peters, Jonathan T.; Peppas, Nicholas A.

    2013-01-01

    Gene therapy is the modification of gene expression to treat a disease. However, efficient intracellular delivery and monitoring of gene therapeutic agents is an ongoing challenge. Use of theranostic agents with suitable targeted, controlled delivery and imaging modalities has the potential to greatly advance gene therapy. Inorganic nanoparticles including magnetic nanoparticles, gold nanoparticles, and quantum dots have been shown to be effective theranostic agents for the delivery and spatiotemporal tracking of oligonucleotides in vitro and even a few cases in vivo. Major concerns remain to be addressed including cytotoxicity, particularly of quantum dots; effective dosage of nanoparticles for optimal theranostic effect; development of real-time in vivo imaging; and further improvement of gene therapy efficacy. PMID:23606894

  15. Using sandpaper for noninvasive transepidermal optical skin clearing agent delivery.

    PubMed

    Stumpp, O; Chen, B; Welch, A J

    2006-01-01

    We present a gentle mechanical method for the noninvasive transepidermal delivery of topically applied optical skin clearing agents. Optical skin clearing reduces light scattering in highly turbid skin with the aid of hyperosmotic chemicals such as glycerol, polyethylene glycol, and solutions of dextrose. Transepidermal delivery of such agents is believed to be most patient compliant and most likely to be used in a clinical environment. Optical skin clearing has the potential to expand the current limited use of laser light in medicine for diagnostic and therapeutic applications. Light scattering limits the penetration depth of collimated light into skin. In order to increase the diffusion of topically applied optical skin clearing agents into skin, we present a gentle mechanical delivery method involving glycerol and dextrose as optical skin clearing agents and fine 220-grit sandpaper to rub the clearing agent into the tissue. Gentle rubbing causes abrasion of the superficial skin layer including the stratum corneum, which otherwise prevents these optical skin clearing agents from freely diffusing into skin. Results indicate very fast optical skin clearing rates. In vivo hamster skin turned transparent within 2 min. The 1e light penetration depth increased by 36+/-3.75% for dextrose and 43+/-8.24% for glycerol. Optical skin clearing was reversed using phosphate buffered saline solution. Skin viability was observed 70 h post-treatment and showed scabbing and erythema on a few percent of the total optically cleared skin surface.

  16. Biodegradable nanoparticles for intracellular delivery of antimicrobial agents.

    PubMed

    Xie, Shuyu; Tao, Yanfei; Pan, Yuanhu; Qu, Wei; Cheng, Guyue; Huang, Lingli; Chen, Dongmei; Wang, Xu; Liu, Zhenli; Yuan, Zonghui

    2014-08-10

    Biodegradable nanoparticles have emerged as a promising strategy for ferrying antimicrobial agents into specific cells due to their unique properties. This review discusses the current progress and challenges of biodegradable nanoparticles for intracellular antimicrobial delivery to understand design principles for the development of ideal nanocarriers. The intracellular delivery performances of biodegradable nanoparticles for diverse antimicrobial agents are first summarized. Second, the cellular internalization and intracellular trafficking, degradation and release kinetics of nanoparticles as well as their relation with intracellular delivery of encapsulated antimicrobial agents are provided. Third, the influences of nanoparticle properties on the cellular internalization and intracellular fate of nanoparticles and their payload antimicrobial agents are discussed. Finally, the challenges and perspectives of nanoparticles for intracellular delivery of antimicrobial agents are addressed. The review will be helpful to the scientists who are interested in searching for more efficient nanosystem strategies for intracellular delivery of antimicrobial agents.

  17. Fabrication and Appraisal of Poly (Lactic-Co-Glycolic Acid) – Moxifloxacin Nanoparticles using Vitamin E-TPGS: A Potential Intracanal Drug Delivery Agent

    PubMed Central

    Patri, Gaurav

    2017-01-01

    Introduction Nanotechnology is gaining momentum in the search for ideal biomaterials by dental researchers. The expansible nature of Endodontology deems exploration, learning and scrutinizing newer avenues which have the potential to be applied and investigated. The popularity of polymers as drug delivery vehicles has opened avenues for their application in the root canal system. This study utilized application of biodegradable polymers as potential drug delivery vehicles against Enterococcus faecalis, one of the main reasons for post treatment disease. Aim This study aimed at fabricating Poly (Lactic-co-Glycolic Acid) (PLGA)-moxifloxacin nanoparticles and assessing its sustained antimicrobial efficacy with calcium hydroxide and chitosan-moxifloxacin hydrogel against Enterococcus faecalis. Materials and Methods PLGA (50:50) in a quantity of 100 mg was dissolved in 1 ml ethyl acetate and 45 ml of 0.3% w/v Vitamin-E Polyethylene Glycol 1000 Succinate (vitamin E-TPGS) was kept for magnetic stirring in separate beaker. Moxifloxacin (50 μl) was added to polymer PLGA following which vitamin E-TPGS was added to the polymer. Nanoparticles were fabricated using ultrasonication and collected by centrifugation. Surface characterization was assessed using scanning electron microscope. Results were obtained in the form of zone of inhibition by the nanoparticles against Enterococcus faecalis and comparisons were made with chitosan-moxifloxacin hydrogel and calcium hydroxide using Analysis of Variance (ANOVA) followed by Student t-test. Results Upon statistical analysis, the zone of inhibition against E. faecalis remained constant with PLGA-moxifloxacin nanoparticles for 14 days while it decreased with chitosan-moxifloxacin hydrogel and remained nil for calcium hydroxide (p<0.01). Conclusion The study posits that PLGA encapsulated moxifloxacin nanoparticles showcased sustained antibacterial effect in low doses against the test pathogen. Its sustained and programmed release makes

  18. Fabrication and Appraisal of Poly (Lactic-Co-Glycolic Acid) - Moxifloxacin Nanoparticles using Vitamin E-TPGS: A Potential Intracanal Drug Delivery Agent.

    PubMed

    Makkar, Hardik; Patri, Gaurav

    2017-06-01

    Nanotechnology is gaining momentum in the search for ideal biomaterials by dental researchers. The expansible nature of Endodontology deems exploration, learning and scrutinizing newer avenues which have the potential to be applied and investigated. The popularity of polymers as drug delivery vehicles has opened avenues for their application in the root canal system. This study utilized application of biodegradable polymers as potential drug delivery vehicles against Enterococcus faecalis, one of the main reasons for post treatment disease. This study aimed at fabricating Poly (Lactic-co-Glycolic Acid) (PLGA)-moxifloxacin nanoparticles and assessing its sustained antimicrobial efficacy with calcium hydroxide and chitosan-moxifloxacin hydrogel against Enterococcus faecalis. PLGA (50:50) in a quantity of 100 mg was dissolved in 1 ml ethyl acetate and 45 ml of 0.3% w/v Vitamin-E Polyethylene Glycol 1000 Succinate (vitamin E-TPGS) was kept for magnetic stirring in separate beaker. Moxifloxacin (50 μl) was added to polymer PLGA following which vitamin E-TPGS was added to the polymer. Nanoparticles were fabricated using ultrasonication and collected by centrifugation. Surface characterization was assessed using scanning electron microscope. Results were obtained in the form of zone of inhibition by the nanoparticles against Enterococcus faecalis and comparisons were made with chitosan-moxifloxacin hydrogel and calcium hydroxide using Analysis of Variance (ANOVA) followed by Student t-test. Upon statistical analysis, the zone of inhibition against E. faecalis remained constant with PLGA-moxifloxacin nanoparticles for 14 days while it decreased with chitosan-moxifloxacin hydrogel and remained nil for calcium hydroxide (p<0.01). The study posits that PLGA encapsulated moxifloxacin nanoparticles showcased sustained antibacterial effect in low doses against the test pathogen. Its sustained and programmed release makes them unique contenders for further evaluation in

  19. TiO2 nanotube arrays deposited on Ti substrate by anodic oxidation and their potential as a long-term drug delivery system for antimicrobial agents

    NASA Astrophysics Data System (ADS)

    Moseke, Claus; Hage, Felix; Vorndran, Elke; Gbureck, Uwe

    2012-05-01

    Nanotube arrays on medical titanium surfaces were fabricated by two different anodization methods and their potential for storage and release of antimicrobial substances was evaluated. The treatment of the Ti surfaces in fluoride containing electrolytes on water as well as on polyethylene glycol basis led to the formation of TiO2 nanotubes with up to 6.54 μm length and average diameters of up to 160 nm. Drug release experiments with the model antibiotic vancomycin and with antibacterial silver ions showed that the increased surface area of the anodized samples enabled them to be loaded with up to 450% more active agent than the untreated Ti surfaces. Significant surface-dependent differences in the release kinetics of vancomycin were observed. In comparison to surfaces anodized in an aqueous electrolyte, the release of the antibiotic from surfaces anodized in an electrolyte based on ethylene glycol was significantly retarded, with a release of noticeable amounts over a period of more than 300 days. Loading of nanotube surfaces fabricated in aqueous electrolyte with silver ions revealed increased amounts of adsorbed silver by up to 230%, while the release kinetics showed significant differences in comparison to untreated Ti. It was concluded that nanotube arrays on favored medical implant materials have a high potential for loading with antimicrobial agents and also provide the possibility of tailored release kinetics by variation of anodization parameters.

  20. Bacteriocins as Potential Anticancer Agents

    PubMed Central

    Kaur, Sumanpreet; Kaur, Sukhraj

    2015-01-01

    Cancer remains one of the leading causes of deaths worldwide, despite advances in its treatment and detection. The conventional chemotherapeutic agents used for the treatment of cancer have non-specific toxicity toward normal body cells that cause various side effects. Secondly, cancer cells are known to develop chemotherapy resistance in due course of treatment. Thus, the demand for novel anti-cancer agents is increasing day by day. Some of the experimental studies have reported the therapeutic potential of bacteriocins against various types of cancer cell lines. Bacteriocins are ribosomally-synthesized cationic peptides secreted by almost all groups of bacteria. Some bacteriocins have shown selective cytotoxicity toward cancer cells as compared to normal cells. This makes them promising candidates for further investigation and clinical trials. In this review article, we present the overview of the various cancer cell-specific cytotoxic bacteriocins, their mode of action and efficacies. PMID:26617524

  1. Nanochemistry of protein-based delivery agents

    NASA Astrophysics Data System (ADS)

    Rajendran, Subin; Udenigwe, Chibuike; Yada, Rickey

    2016-07-01

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

  2. Nanochemistry of Protein-Based Delivery Agents

    PubMed Central

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

    2016-01-01

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

  3. Nanochemistry of Protein-Based Delivery Agents.

    PubMed

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

    2016-01-01

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

  4. Efficient delivery of therapeutic agents by using targeted albumin nanoparticles.

    PubMed

    Kouchakzadeh, Hasan; Safavi, Maryam Sadat; Shojaosadati, Seyed Abbas

    2015-01-01

    Albumin nanoparticles are one of the most important drug carriers for the delivery of therapeutic drugs, especially for the treatment of malignancies. This potential is due to their high binding capacity for both hydrophobic and hydrophilic drugs and the possibility of surface modification. Accumulation of albumin-bound drugs in the tumor interstitium occurs by the enhanced permeability and retention effect, which is also facilitated by the 60-kDa glycoprotein transcytosis pathway and binding to secreted protein, acidic and rich in cysteine located in the tumor extracellular matrix. In addition, specific ligands such as monoclonal antibodies, folic acid, transferrin, and peptides can be conjugated to the surface of albumin nanoparticles to actively target the drug to its site of action. The albumin-bound paclitaxel, Abraxane, is one of the several therapeutic nanocarriers that have been approved for clinical use. By the development of Abraxane that demonstrates a higher response rate and improved tolerability and therapeutic efficiency in comparison with solvent-based formulation, and with consideration of its commercial success, albumin is attracting the interest of many biotechnological and pharmaceutical companies. This chapter explores the current targeted and nontargeted albumin-based nanoparticles that are in various stages of development for the delivery of therapeutic agents in order to enhance the efficacy of cancer treatment.

  5. A Randomized Trial Comparing Skin Antiseptic Agents at Cesarean Delivery

    PubMed Central

    Tuuli, Methodius G.; Liu, Jingxia; Stout, Molly J.; Martin, Shannon; Cahill, Alison G.; Odibo, Anthony O.; Colditz, Graham A.; Macones, George A.

    2016-01-01

    BACKGROUND Preoperative skin antisepsis has the potential to decrease the risk of surgical-site infection. However, evidence is limited to guide the choice of antiseptic agent at cesarean delivery, which is the most common major surgical procedure among women in the United States. METHODS In this single-center, randomized, controlled trial, we evaluated whether the use of chlorhexidine–alcohol for preoperative skin antisepsis was superior to the use of iodine–alcohol for the prevention of surgical-site infection after cesarean delivery. We randomly assigned patients undergoing cesarean delivery to skin preparation with either chlorhexidine–alcohol or iodine–alcohol. The primary outcome was superficial or deep surgical-site infection within 30 days after cesarean delivery, on the basis of definitions from the Centers for Disease Control and Prevention. RESULTS From September 2011 through June 2015, a total of 1147 patients were enrolled; 572 patients were assigned to chlorhexidine–alcohol and 575 to iodine–alcohol. In an intention-to-treat analysis, surgical-site infection was diagnosed in 23 patients (4.0%) in the chlorhexidine–alcohol group and in 42 (7.3%) in the iodine–alcohol group (relative risk, 0.55; 95% confidence interval, 0.34 to 0.90; P = 0.02). The rate of superficial surgical-site infection was 3.0% in the chlorhexidine–alcohol group and 4.9% in the iodine–alcohol group (P = 0.10); the rate of deep infection was 1.0% and 2.4%, respectively (P = 0.07). The frequency of adverse skin reactions was similar in the two groups. CONCLUSIONS The use of chlorhexidine–alcohol for preoperative skin antisepsis resulted in a significantly lower risk of surgical-site infection after cesarean delivery than did the use of iodine–alcohol. (Funded by the National Institutes of Health and Washington University School of Medicine in St. Louis; ClinicalTrials.gov number, NCT01472549.) PMID:26844840

  6. Anti-platelet agents augment cisplatin nanoparticle cytotoxicity by enhancing tumor vasculature permeability and drug delivery

    NASA Astrophysics Data System (ADS)

    Pandey, Ambarish; Sarangi, Sasmit; Chien, Kelly; Sengupta, Poulomi; Papa, Anne-Laure; Basu, Sudipta; Sengupta, Shiladitya

    2014-11-01

    Tumor vasculature is critically dependent on platelet mediated hemostasis and disruption of the same can augment delivery of nano-formulation based chemotherapeutic agents which depend on enhanced permeability and retention for tumor penetration. Here, we evaluated the role of Clopidogrel, a well-known inhibitor of platelet aggregation, in potentiating the tumor cytotoxicity of cisplatin nano-formulation in a murine breast cancer model. In vivo studies in murine syngeneic 4T1 breast cancer model showed a significant greater penetration of macromolecular fluorescent nanoparticles after clopidogrel pretreatment. Compared to self-assembling cisplatin nanoparticles (SACNs), combination therapy with clopidogrel and SACN was associated with a 4 fold greater delivery of cisplatin to tumor tissue and a greater reduction in tumor growth as well as higher survival rate. Clopidogrel enhances therapeutic efficiency of novel cisplatin based nano-formulations agents by increasing tumor drug delivery and can be used as a potential targeting agent for novel nano-formulation based chemotherapeutics.

  7. A haemostatic agent delivery system for endoscopic neurosurgical procedures.

    PubMed

    Waran, V; Sek, K; Bahuri, N F; Narayanan, P; Chandran, H

    2011-10-01

    In endoscopic neurosurgery problems with haemostasis due to poor access exist. We have developed a system which allows the delivery of a variety of haemostatic agents in a more efficacious manner. The system has been used successfully in endoscopic skull base surgery and endoscopic surgery within the parenchyma of the brain using tube systems. © Georg Thieme Verlag KG Stuttgart · New York.

  8. The water-soluble Roussin's red ester acting as a potential photochemical NO-delivery agent: photolysis reactions, DNA cleavage and anticancer activity.

    PubMed

    Chang, Han-Hun; Huang, Hung-Jen; Ho, Yun-Lung; Wen, Yu-Der; Huang, Wei-Ning; Chiou, Show-Jen

    2009-08-28

    The water-soluble Roussin's red ester [(NO)(2)Fe(mu-SCH(2)CH(2)P(O)(CH(2)OH)(2))(2)Fe(NO)(2)] (1), a potential photochemical prodrug of an NO precursor, was synthesized from the reaction of HSCH(2)CH(2)P(O)(CH(2)OH)(2) (F) and [Fe(CO)(2)(NO)(2)]. The IR v(NO) stretching frequencies of complex 1 appear at 1759 (s), 1784 (s) and 1816 (w) cm(-1) in buffer (pH = 7.4). NO was released with a stoichiometry ratio Delta[NO]/Delta[1] = 3.6 +/- 0.2 when complex 1 was exposed to UV in deaerated aqueous phosphate buffer solution. Here light acts as an On/Off switch for NO release. Incubation of pBR322 supercoiled DNA with complex 1, followed by irradiation, produced DNA strand breakage. In contrast to the addition of carboxy-PTIO (NO radical scavenger), DNA strand breakage was not inhibited when the scavengers of hydroxyl radical and singlet oxygen were added. Complex 1 irradiated under a N(2) atmosphere exhibited the same cleavage efficiency as complex 1 irradiated under air. The results show that DNA strand cleavage efficiency depends on the concentration of complex 1, the pH value of the buffer, and the duration of the photolysis of complex 1. The conversion rate from supercoiled (SC form) to nicked circular (NC form) of complex 1 was 2.96 x 10(-2) s(-1). The results of a T4 ligase enzymatic assay reveals the nonhydrolytic DNA breakage mechanism. The NO-release ability of complexes 1, 2, and 3 follows the order 1 > 2 > 3. Upon UV-irradiation, complex 1 exhibits cytotoxicity against B16-F10 mouse melanoma cells.

  9. Nanoparticles as conjugated delivery agents for therapeutic applications

    NASA Astrophysics Data System (ADS)

    Muroski, Megan Elizabeth

    This dissertation explores the use of nanoparticles as conjugated delivery agents. Chapter 1 is a general introduction. Chapter 2 discusses the delivery by a nanoparticle platform provides a method to manipulate gene activation, by taking advantage of the high surface area of a nanoparticle and the ability to selectively couple a desired biological moiety to the NP surface. The nanoparticle based transfection approach functions by controlled release of gene regulatory elements from a 6 nm AuNP (gold nanoparticle) surface. The endosomal release of the regulatory elements from the nanoparticle surface results in endogenous protein knockdown simultaneously with exogenous protein expression for the first 48 h. The use of fluorescent proteins as the endogenous and exogenous signals for protein expression enables the efficiency of co-delivery of siRNA (small interfering RNA) for GFP (green fluorescent protein) knockdown and a dsRed-express linearized plasmid for induction to be optically analyzed in CRL-2794, a human kidney cell line expressing an unstable green fluorescent protein. Delivery of the bimodal nanoparticle in cationic liposomes results in 20% GFP knockdown within 24 h of delivery and continues exhibiting knockdown for up to 48 h for the bimodal agent. Simultaneous dsRed expression is observed to initiate within the same time frame with expression levels reaching 34% after 25 days although cells have divided approximately 20 times, implying daughter cell transfection has occurred. Fluorescence cell sorting results in a stable colony, as demonstrated by Western blot analysis. The simultaneous delivery of siRNA and linearized plasmid DNA on the surface of a single nanocrystal provides a unique method for definitive genetic control within a single cell and leads to a very efficient cell transfection protocol. In Chapter 3, we wanted to understand the NP complex within the cell, and to look at the dynamics of release utilizing nanometal surface energy transfer as

  10. Introduction: Aerosol Delivery of Orally Inhaled Agents

    PubMed Central

    Devadason, Sunalene G.; Kuehl, Philip J.

    2012-01-01

    Abstract Deposition scintigraphy methods have been used extensively to provide qualitative and quantitative data on aerosol drug deposition in the lungs. However, differences in methodology among the different centers performing these studies have limited the application of these techniques, especially in regulatory roles. As an introduction to the standardized techniques developed by the International Society for Aerosols in Medicine (ISAM) Regulatory Affairs Networking Group, we present potential advantages of the use of standard techniques for deposition scintigraphy. Specifically, we propose that standardized techniques would allow for better comparisons between labs and would facilitate multicenter studies. They would allow for improved methods of establishing equivalence and could be better utilized to establish dosing for new medications. They would allow for the performance of more accurate dose ranging or multidose studies and complement pharmacokinetic studies of new inhaled medications. Standardized techniques could help to establish the relationship between the deposition of drug in the lungs and clinical effect, and may also facilitate clinical measurements of deposited dose for medications with narrow therapeutic indices. In the sections that follow, we discuss the best techniques used to perform deposition scintigraphy through planar, single-photon emission computed tomography, and positron emission tomography modalities and propose a detailed set of standardized methods for each. These include methods for radiolabel validation, radiolabel accountability and mass balance, and imaging acquisition and analysis. PMID:23215846

  11. Multirate delivery of multiple therapeutic agents from metal-organic frameworks

    SciTech Connect

    McKinlay, Alistair C.; Allan, Phoebe K.; Renouf, Catherine L.; Duncan, Morven J.; Wheatley, Paul S.; Warrender, Stewart J.; Dawson, Daniel; Ashbrook, Sharon E.; Gil, Barbara; Marszalek, Bartosz; Düren, Tina; Williams, Jennifer J.; Charrier, Cedric; Mercer, Derry K.; Teat, Simon J.; Morris, Russell E.

    2014-12-01

    The highly porous nature of metal-organic frameworks (MOFs) offers great potential for the delivery of therapeutic agents. Here, we show that highly porous metal-organic frameworks can be used to deliver multiple therapeutic agents—a biologically active gas, an antibiotic drug molecule, and an active metal ion—simultaneously but at different rates. The possibilities offered by delivery of multiple agents with different mechanisms of action and, in particular, variable timescales may allow new therapy approaches. Here, we show that the loaded MOFs are highly active against various strains of bacteria.

  12. Multirate delivery of multiple therapeutic agents from metal-organic frameworks

    DOE PAGES

    McKinlay, Alistair C.; Allan, Phoebe K.; Renouf, Catherine L.; ...

    2014-12-01

    The highly porous nature of metal-organic frameworks (MOFs) offers great potential for the delivery of therapeutic agents. Here, we show that highly porous metal-organic frameworks can be used to deliver multiple therapeutic agents—a biologically active gas, an antibiotic drug molecule, and an active metal ion—simultaneously but at different rates. The possibilities offered by delivery of multiple agents with different mechanisms of action and, in particular, variable timescales may allow new therapy approaches. Here, we show that the loaded MOFs are highly active against various strains of bacteria.

  13. Delivery of therapeutic agents by nanoparticles made of grapefruit-derived lipids

    PubMed Central

    Wang, Qilong; Zhuang, Xiaoying; Mu, Jingyao; Deng, Zhong-Bin; Jiang, Hong; Xiang, Xiaoyu; Wang, Baomei; Yan, Jun; Miller, Donald; Zhang, Huang-Ge

    2015-01-01

    Although the use of nanotechnology for the delivery of a wide range of medical treatments has potential to reduce adverse effects associated with drug therapy, tissue-specific delivery remains challenging. Here we show that nanoparticles made of grapefruit-derived lipids, which we call grapefruit-derived nanovectors (GNVs), can transport chemotherapeutic agents, siRNA, DNA expression vectors and proteins to different types of cells. We demonstrate the in vivo targeting specificity of GNVs by co-delivering therapeutic agents with folic acid, which in turn leads to significantly increasing targeting efficiency to cells expressing folate receptors. The therapeutic potential of GNVs was further demonstrated by enhancing the chemotherapeutic inhibition of tumor growth in two tumor animal models. GNVs are less toxic than nanoparticles made of synthetic lipids and, when injected intravenously into pregnant mice, do not pass the placental barrier, suggesting they may be a useful tool for drug delivery. PMID:23695661

  14. Lipid-based cochleates: a promising formulation platform for oral and parenteral delivery of therapeutic agents.

    PubMed

    Rao, Ravi; Squillante, Emilio; Kim, Kwon H

    2007-01-01

    Cochleates are lipid-based supramolecular assemblies that display great potential as delivery systems for systemic delivery of drugs, including peptides, proteins, vaccines, oligonucleotides, and genes. This is mainly attributed to their high stability and biocompatibility and their ability to deliver both hydrophilic and lipophilic drugs. Cochleates have a unique multilayered spiral structure, which is composed of a negatively charged phospholipid and a divalent cation, and can encapsulate diverse drug molecules of various shapes and sizes while minimizing toxicity associated with polymeric materials present in micro- and nanoparticle systems. This review describes current technological advances in the preparation methods, physicochemical characterization, and potential applications of cochleates as a drug delivery system for systemic delivery of various types of therapeutic agents.

  15. Aptamer delivery of siRNA, radiopharmaceutics and chemotherapy agents in cancer.

    PubMed

    de Almeida, Carlos E B; Alves, Lais Nascimento; Rocha, Henrique F; Cabral-Neto, Januário Bispo; Missailidis, Sotiris

    2017-06-20

    Aptamers are oligonucleotide reagents with high affinity and specificity, which among other therapeutic and diagnostic applications have the capability of acting as delivery agents. Thus, aptamers are capable of carrying small molecules, nanoparticles, radiopharmaceuticals or fluorescent agents as well as nucleic acid therapeutics specifically to their target cells. In most cases, the molecules may possess interesting therapeutic properties, but their lack of specificity for a particular cell type, or ability to internalise in such a cell, hinders their clinical development, or cause unwanted side effects. Thus, chemotherapy or radiotherapy agents, famous for their side effects, can be coupled to aptamers for specific delivery. Equally, siRNA have great therapeutic potential and specificity, but one of their shortcomings remain the delivery and internalisation into cells. Various methodologies have been proposed to date, including aptamers, to resolve this problem. Therapeutic or imaging reagents benefit from the adaptability and ease of chemical manipulation of aptamers, their high affinity for the specific marker of a cell type, and their internalisation ability via cell mediated endocytosis. In this review paper, we explore the potential of the aptamers as delivery agents and offer an update on current status and latest advancements. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Novel Bone-Targeting Agent for Enhanced Delivery of Vancomycin to Bone

    PubMed Central

    Albayati, Zaineb A. F.; Sunkara, Manjula; Schmidt-Malan, Suzannah M.; Karau, Melissa J.; Morris, Andrew J.; Steckelberg, James M.; Patel, Robin; Breen, Philip J.; Smeltzer, Mark S.; Taylor, K. Grant; Merten, Kevyn E.

    2015-01-01

    We examined the pharmacokinetic properties of vancomycin conjugated to a bone-targeting agent (BT) with high affinity for hydroxyapatite after systemic intravenous administration. The results confirm enhanced persistence of BT-vancomycin in plasma and enhanced accumulation in bone relative to vancomycin. This suggests that BT-vancomycin may be a potential carrier for the systemic targeted delivery of vancomycin in the treatment of bone infections, potentially reducing the reliance on surgical debridement to achieve the desired therapeutic outcome. PMID:26666918

  17. Implications of nanoscale based drug delivery systems in delivery and targeting tubulin binding agent, noscapine in cancer cells.

    PubMed

    Chandra, Ramesh; Madan, Jitender; Singh, Prashant; Chandra, Ankush; Kumar, Pradeep; Tomar, Vartika; Dass, Sujata K

    2012-12-01

    Noscapine, a tubulin binding anticancer agent undergoing Phase I/II clinical trials, inhibits tumor growth in nude mice bearing human xenografts of breast, lung, ovarian, brain, and prostrate origin. The analogues of noscapine like 9-bromonoscapine (EM011) are 5 to 10-fold more active than parent compound, noscapine. Noscapinoids inhibit the proliferation of cancer cells that are resistant to paclitaxel and epothilone. Noscapine also potentiated the anticancer activity of doxorubicin in a synergistic manner against triple negative breast cancer (TNBC). However, physicochemical and pharmacokinetic (ED50˜300-600 mg/kg bodyweight) limitations of noscapine present hurdle in development of commercial anticancer formulations. Therefore, objectives of the present review are to summarize the chemotherapeutic potential of noscapine and implications of nanoscale based drug delivery systems in enhancing the therapeutic efficacy of noscapine in cancer cells. We have constructed noscapine-enveloped gelatin nanoparticles, NPs and poly (ethylene glycol) grafted gelatin NPs as well as inclusion complex of noscapine in β-cyclodextrin (β-CD) and evaluated their physicochemical characteristics. The Fe3O4 NPs were also used to incorporate noscapine in its polymeric nanomatrix system where molecular weight of the polymer governed the encapsulation efficiency of drug. The enhanced noscapine delivery using μPAR-targeted optical-MR imaging trackable NPs offer a great potential for image directed targeted delivery of noscapine. Human Serum Albumin NPs (150-300 nm) as efficient noscapine drug delivery systems have also been developed for potential use in breast cancer.

  18. Potential new methods for antiepileptic drug delivery.

    PubMed

    Fisher, Robert S; Ho, Jet

    2002-01-01

    Use of novel drug delivery methods could enhance the efficacy and reduce the toxicity of antiepileptic drugs (AEDs). Slow-release oral forms of medication or depot drugs such as skin patches might improve compliance and therefore seizure control. In emergency situations, administration via rectal, nasal or buccal mucosa can deliver the drug more quickly than can oral administration. Slow-release oral forms and rectal forms of AEDs are already approved for use, nasal and buccal administration is currently off-label and skin patches for AEDs are an attractive but currently hypothetical option. Therapies under development may result in the delivery of AEDs directly to the regions of the brain involved in seizures. Experimental protocols are underway to allow continuous infusion of potent excitatory amino acid antagonists into the CSF. In experiments with animal models of epilepsy, AEDs have been delivered successfully to seizure foci in the brain by programmed infusion pumps, acting in response to computerised EEG seizure detection. Inactive prodrugs can be given systemically and activated at the site of the seizure focus by locally released compounds. One such drug under development is DP-VPA (or DP16), which is cleaved to valproic acid (sodium valproate) by phospholipases at the seizure focus. Liposomes and nanoparticles are engineered micro-reservoirs of a drug, with attached antibodies or receptor-specific binding agents designed to target the particles to a specific region of the body. Liposomes in theory could deliver a high concentration of an AED to a seizure focus. Penetration of the blood-brain barrier can be accomplished by linking large particles to iron transferrin or biological toxins that can cross the barrier. In the near future, it is likely that cell transplants that generate neurotransmitters and neuromodulators will accomplish renewable endogenous drug delivery. However, the survival and viability of transplanted cells have yet to be demonstrated

  19. Halloysite clay nanotubes for controlled delivery of chemically active agents

    NASA Astrophysics Data System (ADS)

    Abdullayev, Elshard

    In this work we explored the capabilities of halloysite nanotubes as capsules for encapsulation and controlled delivery of the chemically and biologically active substances. Halloysite is a two-layered aluminosilicate which has a predominantly hollow tubular structure in the submicron range and is chemically similar to kaolinite [1, 2]. In the first section of this work, we analyzed the structure of the halloysite nanotubes as well as its capability to encapsulate and deliver biologically and chemically active agents, similarities and differences between release characteristics of different agents and how these differences relate with their chemical structure. Models were used to describe the release characteristics of the active agents. Study of the interaction between loaded agents and halloysite nanotubes provides better understanding of the release characteristics of the loaded agents and how halloysite can be implemented for technological and medical applications. The second part of the work deals with self-healing coatings produced on the basis of halloysite nanotubes loaded with corrosion inhibitors. Self-healing coatings are one of the effective methods to protect metals from corrosion and deterioration. The difference between self-healing coatings and the usual coatings is the ability of the first to recover after the formation of the damages due to external or internal stresses. High efficiency of the self- healing coatings produced by halloysite nanotubes were demonstrated on 110 Copper alloys and 2024 aluminum alloys. Controlled delivery of the corrosion inhibitors with additional encapsulation of the halloysite nanotubes by synthesizing stoppers at tube endings was also demonstrated. Additional encapsulation of the halloysite nanotubes may be necessary when slow release of the loaded agents is required or rapid convection of the liquid in the surrounding environment takes place (since this may cause rapid release of the loaded agents without additional

  20. Investigation of Degradation Properties of Poly(lactide-co-glycolide) Matrix for Anticancer Agent Delivery

    SciTech Connect

    Ghani, S. M.; Mohamed, M. S. W.; Yahya, A. F.; Noorsal, K.

    2010-03-11

    Poly(lactide-co-glycolide)(PLA{sub 50}GA{sub 50}) is a biodegradable and biocompatible polymer. It offers tremendous potential as a basis for drug delivery, either as drug delivery system alone or in conjugate with a medical device. The PLA{sub 50}GA{sub 50} is the material of choice for relatively shorter-duration applications, while the homopolymer PLA (poly-L-lactide) and PGA (polyglycolide) are preferred for longer term delivery of drugs. This paper discusses the degradation properties of poly(lactide-co-glycolide)(PLA{sub 50}GA{sub 50}) at inherent viscosity of 0.89 dL/g as preliminary studies for anticancer agent delivery.

  1. A Polymeric Bowl for Multi-Agent Delivery.

    PubMed

    Hyun, Dong Choon

    2015-08-01

    This paper describes a simple system for multi-agent delivery. The system consists of a biodegradable polymer particle with a hollow interior, together with a hole on its surface that can be completely or partially sealed via thermal annealing. A hydrophobic dye, Nile-red, entrapped within the shell of hollow particles presents a sustained release behavior while methylene blue, a hydrophilic model agent, encapsulated in the hollow interior shows a fast release manner. The release profiles of the probes can be further independently controlled by encapsulating methylene blue-loaded polymer nanoparticles, instead of free dye, in the hollow particle with a small hole on its surface. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Novel drug delivery approaches on antiviral and antiretroviral agents

    PubMed Central

    Sharma, Pooja; Chawla, Anuj; Arora, Sandeep; Pawar, Pravin

    2012-01-01

    Viruses have the property to replicate very fast in host cell. It can attack any part of host cell. Therefore, the clinical efficacy of antiviral drugs and its bioavailability is more important concern taken into account to treat viral infections. The oral and parenteral routes of drug administration have several shortcomings, however, which could lead to the search for formulating better delivery systems. Now, a day's novel drug delivery systems (NDDS) proved to be a better approach to enhance the effectiveness of the antivirals and improve the patient compliance and decrease the adverse effect. The NDDS have reduced the dosing frequency and shorten the duration of treatment, thus, which could lead the treatment more cost-effective. The development of NDDS for antiviral and antiretroviral therapy aims to deliver the drug devoid of toxicity, with high compatibility and biodegradability, targeting the drug to specific sites for viral infection and in some instances it also avoid the first pass metabolism effect. This article aims to discuss the usefulness of novel delivery approaches of antiviral agents such as niosomes, microspheres, microemulsions, nanoparticles that are used in the treatment of various Herpes viruses and in human immunodeficiency virus (HIV) infections. PMID:23057001

  3. Nanocarriers for Vascular Delivery of Anti-Inflammatory Agents

    PubMed Central

    Howard, Melissa D.; Hood, Elizabeth D.; Zern, Blaine; Shuvaev, Vladimir V.; Grosser, Tilo; Muzykantov, Vladimir R.

    2017-01-01

    There is a need for improved treatment of acute vascular inflammation in conditions such as ischemia-reperfusion injury, acute lung injury, sepsis, and stroke. The vascular endothelium represents an important therapeutic target in these conditions. Furthermore, some anti-inflammatory agents (AIAs) (e.g., biotherapeutics) require precise delivery into subcellular compartments. In theory, optimized delivery to the desired site of action may improve the effects and enable new mechanisms of action of these AIAs. Diverse nanocarriers (NCs) and strategies for targeting them to endothelial cells have been designed and explored for this purpose. Studies in animal models suggest that delivery of AIAs using NCs may provide potent and specific molecular interventions in inflammatory pathways. However, the industrial development and clinical translation of complex NC-AIA formulations are challenging. Rigorous analysis of therapeutic/side effect and benefit/cost ratios is necessary to identify and optimize the approaches that may find clinical utility in the management of acute inflammation. PMID:24392694

  4. Zirconium Phosphate Nanoplatelet Potential for Anticancer Drug Delivery Applications.

    PubMed

    González, Millie L; Ortiz, Mayra; Hernández, Carmen; Cabán, Jennifer; Rodríguez, Axel; Colón, Jorge L; Báez, Adriana

    2016-01-01

    Zirconium phosphate (ZrP) nanoplatelets can intercalate anticancer agents via an ion exchange reaction creating an inorganic delivery system with potential for cancer treatment. ZrP delivery of anticancer agents inside tumor cells was explored in vitro. Internalization and cytotoxicity of ZrP nanoplatelets were studied in MCF-7 and MCF-10A cells. DOX-loaded ZrP nanoplatelets (DOX@ZrP) uptake was assessed by confocal (CLSM) and transmission electron microscopy (TEM). Cytotoxicity to MCF-7 and MCF-10A cells was determined by the MTT assay. Reactive Oxy- gen Species (ROS) production was analyzed by fluorometric assay, and cell cycle alterations and induction of apoptosis were analyzed by flow cytometry. ZrP nanoplatelets were localized in the endosomes of MCF-7 cells. DOX and ZrP nanoplatelets were co-internalized into MCF-7 cells as detected by CLSM. While ZrP showed limited toxicity to MCF-7 cells, DOX@ZrP was cytotoxic at an IC₅₀ similar to that of free DOX. Meanwhile, DOX lC₅₀ was significantly lower than the equivalent concentration of DOX@ZrP in MCF-10A cells. ZrP did not induce apoptosis in both cell lines. DOX and DOX@ZrP induced significant oxidative stress in both cell models. Results suggest that ZrP nanoplatelets are promising as carriers of anticancer agents into cancer cells.

  5. Convection-Enhanced Delivery for Targeted Delivery of Antiglioma Agents: The Translational Experience

    PubMed Central

    Yun, Jonathan; Rothrock, Robert J.; Canoll, Peter; Bruce, Jeffrey N.

    2013-01-01

    Recent improvements in the understanding of glioblastoma (GBM) have allowed for increased ability to develop specific, targeted therapies. In parallel, however, there is a need for effective methods of delivery to circumvent the therapeutic obstacles presented by the blood-brain barrier and systemic side effects. The ideal delivery system should allow for adequate targeting of the tumor while minimizing systemic exposure, applicability across a wide range of potential therapies, and have existing safe and efficacious systems that allow for widespread application. Though many alternatives to systemic delivery have been developed, this paper will focus on our experience with convection-enhanced delivery (CED) and our focus on translating this technology from pre-clinical studies to the treatment of human GBM. PMID:23476784

  6. pH-Sensitive stimulus-responsive nanocarriers for targeted delivery of therapeutic agents

    PubMed Central

    Karimi, Mahdi; Eslami, Masoud; Sahandi-Zangabad, Parham; Mirab, Fereshteh; Farajisafiloo, Negar; Shafaei, Zahra; Ghosh, Deepanjan; Bozorgomid, Mahnaz; Dashkhaneh, Fariba; Hamblin, Michael R.

    2016-01-01

    In recent years miscellaneous smart micro/nanosystems that respond to various exogenous/endogenous stimuli including temperature, magnetic/electric field, mechanical force, ultrasound/light irradiation, redox potentials, and biomolecule concentration have been developed for targeted delivery and release of encapsulated therapeutic agents such as drugs, genes, proteins, and metal ions specifically at their required site of action. Owing to physiological differences between malignant and normal cells, or between tumors and normal tissues, pH-sensitive nanosystems represent promising smart delivery vehicles for transport and delivery of anticancer agents. Furthermore, pH-sensitive systems possess applications in delivery of metal ions and biomolecules such as proteins, insulin, etc., as well as co-delivery of cargos, dual pH-sensitive nanocarriers, dual/multi stimuli-responsive nanosystems, and even in the search for new solutions for therapy of diseases such as Alzheimer’s. In order to design an optimized system, it is necessary to understand the various pH-responsive micro/nanoparticles and the different mechanisms of pH-sensitive drug release. This should be accompanied by an assessment of the theoretical and practical challenges in the design and use of these carriers. PMID:26762467

  7. Biological delivery approaches for gene therapy: strategies to potentiate efficacy and enhance specificity.

    PubMed

    Mohit, Elham; Rafati, Sima

    2013-12-01

    Nowadays many therapeutic agents such as suicide genes, anti-angiogenesis agents, cytokines, chemokines and other therapeutic genes were delivered to cancer cells. Various biological delivery systems have been applied for directing therapeutic gene to target cells. Some of these successful preclinical studies, steps forward to clinical trials and a few are examined in phase III clinical trials. In this review, the biological gene delivery systems were categorized into microorganism and cell based delivery systems. Viral, bacterial, yeast and parasite are among microorganism based delivery systems which are expanded in this review. In cell based approach, different strategies such as tumor cells, stem cells, dendritic cells and sertoli cells will be discussed. Different drawbacks are associated with each delivery system; therefore, many strategies have been improved and potentiated their direction toward specific target cells. Herein, further to the principle of each delivery system, the progresses of these approaches for development of newer generation are discussed.

  8. Nanoscaled boron-containing delivery systems and therapeutic agents for cancer treatment.

    PubMed

    Wang, Jing; Wu, Wei; Jiang, Xiqun

    2015-01-01

    Significant efforts have recently been made to develop nanoscaled boron-containing delivery systems for improving drug delivery in cancer therapy. On one hand, borate ester chemistry has shown importance in ligand-mediated tumor targeting owing to the recognition ability of boronic acid to polyol residues in cell membranes. In particular, the phenylboronic acid-functionalized nanocarriers for specific targeting to sialic acid groups which are overexpressed on tumor cells have made great achievements. On the other hand, nanoscaled boron neutron capture therapy agents show growing potential in efficiently transporting boron to tumor. The current review outlines the recent developments in the application of borate ester chemistry in tumor targeting by nanoparticles, then summarizes recent work on the development of boron-based nanomaterials as boron neutron capture therapy agents.

  9. Polymeric protective agents for nanoparticles in drug delivery and targeting.

    PubMed

    Mogoşanu, George Dan; Grumezescu, Alexandru Mihai; Bejenaru, Cornelia; Bejenaru, Ludovic Everard

    2016-08-30

    Surface modification/functionalization of nanoparticles (NPs) using polymeric protective agents is an issue of great importance and actuality for drug delivery and targeting. Improving the blood circulation half-life of surface-protected nanocarriers is closely related to the elimination of main biological barriers and limiting factors (protein absorption and opsonization), due to the phagocytic activity of reticuloendothelial system. For passive or active targeted delivery, in biomedical area, surface-functionalized NPs with tissue-recognition ligands were designed and optimized as a result of modern research techniques. Also, multi-functionalized nanostructures are characterized by enhanced bioavailability, efficacy, targeted localization, active cellular uptake, and low side effects. Surface-protected NPs are obtained from biocompatible, biodegradable and less toxic natural polymers (dextran, β-cyclodextrin, chitosan, hyaluronic acid, heparin, gelatin) or synthetic polymers, such as poly(lactic acid), poly(lactic-co-glycolic) acid, poly(ε-caprolactone) and poly(alkyl cyanoacrylates). PEGylation is one of the most important functionalization methods providing steric stabilization, long circulating and 'stealth' properties for both polymeric and inorganic-based nanosystems. In addition, for their antimicrobial, antiviral and antitumor effects, cutting-edge researches in the field of pharmaceutical nanobiotechnology highlighted the importance of noble metal (platinum, gold, silver) NPs decorated with biopolymers. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Delivery of active agents from chewing gum for improved remineralization.

    PubMed

    Dodds, M W J; Chidichimo, D; Haas, M S

    2012-09-01

    Most surrogate measures of caries were developed to test products containing fluoride, typically at relatively high and closely controlled oral concentrations. However, since the primary mechanism for the remineralization of early enamel caries lesions by chewing gum is through stimulation of saliva, delivering Ca and Pi to the demineralized enamel lesion, established methods may lack the sensitivity to detect the additional benefit of an active agent without the strong remineralizing potential of fluoride. Issues related to the release of active agents from the gum matrix, dilution in the saliva, and limited oral retention time, along with taste, safety, regulatory, and cost concerns, impose further limitations. This paper reviews the efficacy of some active agents used in chewing gum for improved remineralization and includes results from in situ testing of calcium-containing gums, including calcium lactate, tetracalcium phosphate/dicalcium phosphate anhydrous, calcium citrate/encapsulated phosphate, and a calcium lactate/sodium phosphate blend. Despite promising in vitro data from these agents, they did not provide consistently superior results from in situ testing. There is a need to develop better predictive in vitro models for chewing gum, as well as improved sensitivity of in situ models to discriminate relatively small amounts of remineralization against a background of high biological variability.

  11. Towards Engineering Hormone-Binding Globulins as Drug Delivery Agents

    PubMed Central

    Chan, Wee Lee; Zhou, Aiwu; Read, Randy J.

    2014-01-01

    The treatment of many diseases such as cancer requires the use of drugs that can cause severe side effects. Off-target toxicity can often be reduced simply by directing the drugs specifically to sites of diseases. Amidst increasingly sophisticated methods of targeted drug delivery, we observed that Nature has already evolved elegant means of sending biological molecules to where they are needed. One such example is corticosteroid binding globulin (CBG), the major carrier of the anti-inflammatory hormone, cortisol. Targeted release of cortisol is triggered by cleavage of CBG's reactive centre loop by elastase, a protease released by neutrophils in inflamed tissues. This work aimed to establish the feasibility of exploiting this mechanism to carry therapeutic agents to defined locations. The reactive centre loop of CBG was altered with site-directed mutagenesis to favour cleavage by other proteases, to alter the sites at which it would release its cargo. Mutagenesis succeeded in making CBG a substrate for either prostate specific antigen (PSA), a prostate-specific serine protease, or thrombin, a key protease in the blood coagulation cascade. PSA is conspicuously overproduced in prostatic hyperplasia and is, therefore, a good way of targeting hyperplastic prostate tissues. Thrombin is released during clotting and consequently is ideal for conferring specificity to thrombotic sites. Using fluorescence-based titration assays, we also showed that CBG can be engineered to bind a new compound, thyroxine-6-carboxyfluorescein, instead of its physiological ligand, cortisol, thereby demonstrating that it is possible to tailor the hormone binding site to deliver a therapeutic drug. In addition, we proved that the efficiency with which CBG releases bound ligand can be increased by introducing some well-placed mutations. This proof-of-concept study has raised the prospect of a novel means of targeted drug delivery, using the serpin conformational change to combat the problem of

  12. Therapeutic potential of chalcones as cardiovascular agents.

    PubMed

    Mahapatra, Debarshi Kar; Bharti, Sanjay Kumar

    2016-03-01

    Cardiovascular diseases are the leading cause of death affecting 17.3 million people across the globe and are estimated to affect 23.3 million people by year 2030. In recent years, about 7.3 million people died due to coronary heart disease, 9.4 million deaths due to high blood pressure and 6.2 million due to stroke, where obesity and atherosclerotic progression remain the chief pathological factors. The search for newer and better cardiovascular agents is the foremost need to manage cardiac patient population across the world. Several natural and (semi) synthetic chalcones deserve the credit of being potential candidates to inhibit various cardiovascular, hematological and anti-obesity targets like angiotensin converting enzyme (ACE), cholesteryl ester transfer protein (CETP), diacylglycerol acyltransferase (DGAT), acyl-coenzyme A: cholesterol acyltransferase (ACAT), pancreatic lipase (PL), lipoprotein lipase (LPL), calcium (Ca(2+))/potassium (K(+)) channel, COX-1, TXA2 and TXB2. In this review, a comprehensive study of chalcones, their therapeutic targets, structure activity relationships (SARs), mechanisms of actions (MOAs) have been discussed. Chemically diverse chalcone scaffolds, their derivatives including structural manipulation of both aryl rings, replacement with heteroaryl scaffold(s) and hybridization through conjugation with other pharmacologically active scaffold have been highlighted. Chalcones which showed promising activity and have a well-defined MOAs, SARs must be considered as prototype for the design and development of potential anti-hypertensive, anti-anginal, anti-arrhythmic and cardioprotective agents. With the knowledge of these molecular targets, structural insights and SARs, this review may be helpful for (medicinal) chemists to design more potent, safe, selective and cost effective chalcone derivatives as potential cardiovascular agents. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Ocular delivery systems for topical application of anti-infective agents.

    PubMed

    Duxfield, Linda; Sultana, Rubab; Wang, Ruokai; Englebretsen, Vanessa; Deo, Samantha; Rupenthal, Ilva D; Al-Kassas, Raida

    2016-01-01

    For the treatment of anterior eye segment infections using anti-infective agents, topical ocular application is the most convenient route of administration. However, topical delivery of anti-infective agents is associated with a number of problems and challenges owing to the unique structure of the eye and the physicochemical properties of these compounds. Topical ocular drug delivery systems can be classified into two forms: conventional and non-conventional. The efficacy of conventional ocular formulations is limited by poor corneal retention and permeation resulting in low ocular bioavailability. Recently, attention has been focused on improving topical ocular delivery of anti-infective agents using advanced drug delivery systems. This review will focus on the challenges of efficient topical ocular delivery of anti-infective agents and will discuss the various types of delivery systems used to improve the treatment anterior segment infections.

  14. Rodents as potential couriers for bioterrorism agents.

    PubMed

    Lõhmus, Mare; Janse, Ingmar; van de Goot, Frank; van Rotterdam, Bart J

    2013-09-01

    Many pathogens that can cause major public health, economic, and social damage are relatively easily accessible and could be used as biological weapons. Wildlife is a natural reservoir for many potential bioterrorism agents, and, as history has shown, eliminating a pathogen that has dispersed among wild fauna can be extremely challenging. Since a number of wild rodent species live close to humans, rodents constitute a vector for pathogens to circulate among wildlife, domestic animals, and humans. This article reviews the possible consequences of a deliberate spread of rodentborne pathogens. It is relatively easy to infect wild rodents with certain pathogens or to release infected rodents, and the action would be difficult to trace. Rodents can also function as reservoirs for diseases that have been spread during a bioterrorism attack and cause recurring disease outbreaks. As rats and mice are common in both urban and rural settlements, deliberately released rodentborne infections have the capacity to spread very rapidly. The majority of pathogens that are listed as potential agents of bioterrorism by the Centers for Disease Control and Prevention and the National Institute of Allergy and Infectious Diseases exploit rodents as vectors or reservoirs. In addition to zoonotic diseases, deliberately released rodentborne epizootics can have serious economic consequences for society, for example, in the area of international trade restrictions. The ability to rapidly detect introduced diseases and effectively communicate with the public in crisis situations enables a quick response and is essential for successful and cost-effective disease control.

  15. Potential of immunosuppressive agents in cerebral ischaemia

    PubMed Central

    Gupta, Yogendra Kumar; Chauhan, Anjali

    2011-01-01

    Ischaemic stroke is a disorder involving multiple mechanisms of injury progression including activation of glutamate receptors, release of proinflammatory cytokines, nitric oxide (NO), free oxygen radicals and proteases. Presently, recombinant tissue plasminogen activator (rtPA) is the only drug approved for the management of acute ischaemic stroke. This drug, however, is associated with limitations like narrow therapeutic window and increased risk of intracranial haemorrhage. A large number of therapeutic agents have been tested including N-methly-D-aspartate (NMDA) receptor antagonist, calcium channel blockers and antioxidants for management of stroke, but none has provided significant neuroprotection in clinical trials. Therefore, searching for other potentially effective drugs for ischaemic stroke management becomes important. Immunosuppressive agents with their wide array of mechanisms have potential as neuroprotectants. Corticosteroids, immunophilin ligands, mycophenolate mofetil and minocycline have shown protective effect on neurons by their direct actions or attenuating toxic effects of mediators of inflammation. This review focuses on the current status of corticosteroids, cyclosporine A, FK506, rapamycin, mycophenolate mofetil and minocycline in the experimental models of cerebral ischaemia. PMID:21321416

  16. Brucella as a potential agent of bioterrorism.

    PubMed

    Doganay, Gizem D; Doganay, Mehmet

    2013-04-01

    Perception on bioterrorism has changed after the deliberate release of anthrax by the postal system in the United States of America in 2001. Potential bioterrorism agents have been reclassified based on their dissemination, expected rate of mortality, availability, stability, and ability to lead a public panic. Brucella species can be easily cultured from infected animals and human materials. Also, it can be transferred, stored and disseminated easily. An intentional contamination of food with Brucella species could pose a threat with low mortality rate. Brucella spp. is highly infectious through aerosol route, making it an attractive pathogen to be used as a potential agent for biological warfare purposes. Recently, many studies have been concentrated on appropriate sampling of Brucella spp. from environment including finding ways for its early detection and development of new decontamination procedures such as new drugs and vaccines. There are many ongoing vaccine development studies; some of which recently received patents for detection and therapy of Brucella spp. However, there is still no available vaccine for humans. In this paper, recent developments and recent patents on brucellosis are reviewed and discussed.

  17. Future Directions in Pain Management: Integrating Anatomically Selective Delivery Techniques With Novel Molecularly Selective Agents.

    PubMed

    Pleticha, Josef; Maus, Timothy P; Beutler, Andreas S

    2016-04-01

    Treatment for chronic, locoregional pain ranks among the most prevalent unmet medical needs. The failure of systemic analgesic drugs, such as opioids, is often due to their off-target toxicity, development of tolerance, and abuse potential. Interventional pain procedures provide target specificity but lack pharmacologically selective agents with long-term efficacy. Gene therapy vectors are a new tool for the development of molecularly selective pain therapies, which have already been proved to provide durable analgesia in preclinical models. Taken together, advances in image-guided delivery and gene therapy may lead to a new class of dual selective analgesic treatments integrating the molecular selectivity of analgesic genes with the anatomic selectivity of interventional delivery techniques.

  18. TRPV1 antagonists as potential antitussive agents.

    PubMed

    McLeod, Robbie L; Correll, Craig C; Jia, Yanlin; Anthes, John C

    2008-01-01

    Cough is an important defensive pulmonary reflex that removes irritants, fluids, or foreign materials from the airways. However, when cough is exceptionally intense or when it is chronic and/or nonproductive it may require pharmacologic suppression. For many patients, antitussive therapies consist of OTC products with inconsequential efficacies. On the other hand, the prescription antitussive market is dominated by older opioid drugs such as codeine. Unfortunately, "codeine-like" drugs suppress cough at equivalent doses that also often produce significant ancillary liabilities such as GI constipation, sedation, and respiratory depression. Thus, the discovery of a novel and effective antitussive drug with an improved side effect profile relative to codeine would fulfill an unmet clinical need in the treatment of cough. Afferent pulmonary nerves are endowed with a multitude of potential receptor targets, including TRPV1, that could act to attenuate cough. The evidence linking TRPV1 to cough is convincing. TRPV1 receptors are found on sensory respiratory nerves that are important in the generation of the cough reflex. Isolated pulmonary vagal afferent nerves are responsive to TRPV1 stimulation. In vivo, TRPV1 agonists such as capsaicin elicit cough when aerosolized and delivered to the lungs. Pertinent to the debate on the potential use of TRPV1 antagonist as antitussive agents are the observations that airway afferent nerves become hypersensitive in diseased and inflamed lungs. For example, the sensitivity of capsaicin-induced cough responses following upper respiratory tract infection and in airway inflammatory diseases such as asthma and COPD is increased relative to that of control responses. Indeed, we have demonstrated that TRPV1 antagonism can attenuate antigen-induced cough in the allergic guinea pig. However, it remains to be determined if the emerging pharmacologic profile of TRPV1 antagonists will translate into a novel human antitussive drug. Current

  19. Plants' metabolites as potential antiobesity agents.

    PubMed

    Gooda Sahib, Najla; Saari, Nazamid; Ismail, Amin; Khatib, Alfi; Mahomoodally, Fawzi; Abdul Hamid, Azizah

    2012-01-01

    Obesity and obesity-related complications are on the increase both in the developed and developing world. Since existing pharmaceuticals fail to come up with long-term solutions to address this issue, there is an ever-pressing need to find and develop new drugs and alternatives. Natural products, particularly medicinal plants, are believed to harbor potential antiobesity agents that can act through various mechanisms either by preventing weight gain or promoting weight loss amongst others. The inhibition of key lipid and carbohydrate hydrolyzing and metabolizing enzymes, disruption of adipogenesis, and modulation of its factors or appetite suppression are some of the plethora of targeted approaches to probe the antiobesity potential of medicinal plants. A new technology such as metabolomics, which deals with the study of the whole metabolome, has been identified to be a promising technique to probe the progression of diseases, elucidate their pathologies, and assess the effects of natural health products on certain pathological conditions. This has been applied to drug research, bone health, and to a limited extent to obesity research. This paper thus endeavors to give an overview of those plants, which have been reported to have antiobesity effects and highlight the potential and relevance of metabolomics in obesity research.

  20. Plants' Metabolites as Potential Antiobesity Agents

    PubMed Central

    Gooda Sahib, Najla; Saari, Nazamid; Ismail, Amin; Khatib, Alfi; Mahomoodally, Fawzi; Abdul Hamid, Azizah

    2012-01-01

    Obesity and obesity-related complications are on the increase both in the developed and developing world. Since existing pharmaceuticals fail to come up with long-term solutions to address this issue, there is an ever-pressing need to find and develop new drugs and alternatives. Natural products, particularly medicinal plants, are believed to harbor potential antiobesity agents that can act through various mechanisms either by preventing weight gain or promoting weight loss amongst others. The inhibition of key lipid and carbohydrate hydrolyzing and metabolizing enzymes, disruption of adipogenesis, and modulation of its factors or appetite suppression are some of the plethora of targeted approaches to probe the antiobesity potential of medicinal plants. A new technology such as metabolomics, which deals with the study of the whole metabolome, has been identified to be a promising technique to probe the progression of diseases, elucidate their pathologies, and assess the effects of natural health products on certain pathological conditions. This has been applied to drug research, bone health, and to a limited extent to obesity research. This paper thus endeavors to give an overview of those plants, which have been reported to have antiobesity effects and highlight the potential and relevance of metabolomics in obesity research. PMID:22666121

  1. Utilization of biodegradable polymeric materials as delivery agents in dermatology

    PubMed Central

    Rancan, Fiorenza; Blume-Peytavi, Ulrike; Vogt, Annika

    2014-01-01

    Biodegradable polymeric materials are ideal carrier systems for biomedical applications. Features like controlled and sustained delivery, improved drug pharmacokinetics, reduced side effects and safe degradation make the use of these materials very attractive in a lot of medical fields, with dermatology included. A number of studies have shown that particle-based formulations can improve the skin penetration of topically applied drugs. However, for a successful translation of these promising results into a clinical application, a more rational approach is needed to take into account the different properties of diseased skin and the fate of these polymeric materials after topical application. In fact, each pathological skin condition poses different challenges and the way diseased skin interacts with polymeric carriers might be markedly different to that of healthy skin. In most inflammatory skin conditions, the skin’s barrier is impaired and the local immune system is activated. A better understanding of such mechanisms has the potential to improve the efficacy of carrier-based dermatotherapy. Such knowledge would allow the informed choice of the type of polymeric carrier depending on the skin condition to be treated, the type of drug to be loaded, and the desired release kinetics. Furthermore, a better control of polymer degradation and release properties in accordance with the skin environment would improve the safety and the selectivity of drug release. This review aims at summarizing the current knowledge on how polymeric delivery systems interact with healthy and diseased skin, giving an overview of the challenges that different pathological skin conditions pose to the development of safer and more specific dermatotherapies. PMID:24470766

  2. The influence of agent delivery mode on cardiomyocyte injury induced by myocardial contrast echocardiography in rats.

    PubMed

    Miller, Douglas L; Dou, Chunyan; Armstrong, William F

    2005-09-01

    Myocardial contrast echocardiography (MCE) can induce bioeffects in rat hearts by local activation of the contrast agent gas bodies. This study was designed to examine the influence of agent delivery mode on the magnitude of cardiomyocyte injury. A total of 69 hairless rats were anesthetized and mounted vertically in a water bath. Evans blue dye was injected as vital stain for cardiomyocyte injury. Definity contrast agent was diluted in saline and injected via tail vein at 20 or 80 microL/kg in bolus or infusion mode. In 12 rats, 0.57 mg/kg dipyridamole was given to simulate a stress test. MCE in a short axis view with 1:4 or 1:16 ECG triggering was performed at 1.5 MHz for 5 or 20 min. The peak rarefactional pressure amplitude was set to 1.1 or 2.0 MPa. Premature beats were counted from the ECG record. Evans blue fluorescent cells were counted on frozen sections from the center of the scan plane of heart samples obtained 24 h postMCE. Infusion of the contrast agent led to more cardiomyocyte injury than did bolus injection. Dipyridamole stress also increased the effect. Varying the infusion rate or trigger interval was less important than the overall dosage during scanning. Exposure at 1.1 MPa and 80 microL/kg yielded significant cell killing relative to shams. Premature beats generally followed the same trends as cell injury, except that lower infusion rates tended to increase this effect. Contrast agent delivery mode, as well as dose and peak rarefactional pressure amplitude, has a significant influence on the bioeffects potential of MCE.

  3. Polypodium leucotomos: a potential new photoprotective agent.

    PubMed

    Bhatia, Neal

    2015-04-01

    As the understanding of the immune system pathways, cytokine balances, and cellular interactions continues to expand, so must the potential applications of therapies that can impact the process of diseases instead of just controlling their symptoms. In the case of Polypodium leucotomos extract, which is derived from a tropical fern of the Polypodiaceae family, the future potential of applications in dermatology and beyond will be better understood as its incorporation into daily routines gives rise to the development of new regimens. Clinicians may position this agent as an option for daily maintenance, accept its use in combinations, or use it as a template for further development of oral supplementation that may evolve into a true immunomodulator. The antioxidant activity of P. leucotomos extract is primarily driven by caffeic acid and ferulic acid, resulting in the control of cutaneous responses to ultraviolet-induced erythema, in the interception of inflammatory mechanisms, and the promotion of other cytotoxic responses. Histologically, the impact of P. leucotomos extract induces an effect on the overall reduction of angiogenesis, photocarcinogenesis, and solar elastosis, while on the cellular level there are improvements in cell membrane integrity and elastin expression. Future applications for P. leucotomos extract could include the potential for photoprotective effects, and subsequent research efforts should focus on determining the optimal dosage regimen, duration of action, and utility of combinations with sunscreens, among other outcomes. Recently published data have also demonstrated how the antioxidant effects of oral P. leucotomos extract can delay tumor development in mice models, suggesting there might be a protective role that could be described with further clinical research. In addition, it is important to recognize the distinction between photoprotection and chemoprevention, in that there has yet to be any in vivo or controlled clinical trial

  4. Drug delivery to the testis: current status and potential pathways for the development of novel therapeutics.

    PubMed

    Snow-Lisy, Devon C; Samplaski, Mary K; Labhasetwar, Vinod; Sabanegh, Edmund S

    2011-10-01

    Nanotechnology has been increasingly utilized for the targeting and delivery of novel therapeutic agents to different tissues and cell types. The current therapeutic options for testicular disorders fall short in many instances due to difficulty traversing the blood-testis barrier, systemic toxicities, and complicated dosing regiments. For testicular tissue, potential targeting can be obtained either via anatomic methods or specific ligands such as luteinizing hormone or follicle-stimulating hormone analogs. Potential novel therapeutic agents include DNA, RNA, cytokines, peptide receptor antagonists, peptide receptor agonists, hormones, and enzymes. Nanotherapeutic treatment of testicular cancer, infertility, testicular torsion, orchalgia, hypogonadism, testicular infections, and cryptorchidism within the framework of potential target cells are an emerging area of research. While there are many potential applications of nanotechnology in drug delivery to the testis, this remains a relatively unexplored field. This review highlights the current status as well as potential future of nanotechnology in the development of novel therapeutics for testicular disorders.

  5. Nigella sativa: A Potential Antiosteoporotic Agent

    PubMed Central

    Shuid, Ahmad Nazrun; Mohamed, Norazlina; Mohamed, Isa Naina; Othman, Faizah; Suhaimi, Farihah; Mohd Ramli, Elvy Suhana; Muhammad, Norliza; Soelaiman, Ima Nirwana

    2012-01-01

    Nigella sativa seeds (NS) has been used traditionally for various illnesses. The most abundant and active component of NS is thymoquinone (TQ). Animal studies have shown that NS and TQ may be used for the treatment of diabetes-induced osteoporosis and for the promotion of fracture healing. The mechanism involved is unclear, but it was postulated that the antioxidative, and anti-inflammatory activities may play some roles in the treatment of osteoporosis as this bone disease has been linked to oxidative stress and inflammation. This paper highlights studies on the antiosteoporotic effects of NS and TQ, the mechanisms behind these effects and their safety profiles. NS and TQ were shown to inhibit inflammatory cytokines such as interleukin-1 and 6 and the transcription factor, nuclear factor κB. NS and TQ were found to be safe at the current dosage for supplementation in human with precautions in children and pregnant women. Both NS and TQ have shown potential as antiosteoporotic agent but more animal and clinical studies are required to further assess their antiosteoporotic efficacies. PMID:22973403

  6. Cellular Delivery and Photochemical Activation of Antisense Agents through a Nucleobase Caging Strategy

    PubMed Central

    Govan, Jeane M.; Uprety, Rajendra; Thomas, Meryl; Lusic, Hrvoje; Lively, Mark O.; Deiters, Alexander

    2013-01-01

    Antisense oligonucleotides are powerful tools to regulate gene expression in cells and model organisms. However, a transfection or microinjection is needed for efficient delivery of the antisense agent. We report the conjugation of multiple HIV TAT peptides to a hairpin-protected antisense agent through a light-cleavable nucleobase caging group. This conjugation allows for the facile delivery of the antisense agent without a transfection reagent and photochemical activation offers precise control over gene expression. The developed approach is highly modular, as demonstrated by the conjugation of folic acid to the caged antisense agent. This enabled targeted cell delivery through cell-surface folate receptors followed by photochemical triggering of antisense activity. Importantly, the presented strategy delivers native oligonucleotides after light-activation, devoid of any delivery functionalities or modifications that could otherwise impair their antisense activity. PMID:23915424

  7. Bioactive peroxides as potential therapeutic agents.

    PubMed

    Dembitsky, Valery M

    2008-02-01

    Present review describes research on more than 280 natural anticancer agents isolated from terrestrial and marine sources and synthetic biologically active peroxides. Intensive searches for new classes of pharmacologically potent agents produced by terrestrial and marine organisms have resulted in the discovery of dozens of compounds possessing high cytotoxic, antibacterial, antimalarial, and other activities as an important source of leads for drug discovery.

  8. Biological agents with potential for misuse: a historical perspective and defensive measures.

    PubMed

    Bhalla, Deepak K; Warheit, David B

    2004-08-15

    Biological and chemical agents capable of producing serious illness or mortality have been used in biowarfare from ancient times. Use of these agents has progressed from crude forms in early and middle ages, when snakes and infected cadavers were used as weapons in battles, to sophisticated preparations for use during and after the second World War. Cults and terrorist organizations have attempted the use of biological agents with an aim to immobilize populations or cause serious harm. The reasons for interest in these agents by individuals and organizations include relative ease of acquisition, potential for causing mass casualty or panic, modest financing requirement, availability of technology, and relative ease of delivery. The Centers for Disease Control and Prevention has classified Critical Biological Agents into three major categories. This classification was based on several criteria, which include severity of impact on human health, potential for delivery in a weapon, capacity to cause panic and special needs for development, and stockpiling of medication. Agents that could cause the greatest harm following deliberate use were placed in category A. Category B included agents capable of producing serious harm and significant mortality but of lower magnitude than category A agents. Category C included emerging pathogens that could be developed for mass dispersion in future and their potential as a major health threat. A brief description of the category A bioagents is included and the pathophysiology of two particularly prominent agents, namely anthrax and smallpox, is discussed in detail. The potential danger from biological agents and their ever increasing threat to human populations have created a need for developing technologies for their early detection, for developing treatment strategies, and for refinement of procedures to ensure survival of affected individuals so as to attain the ultimate goal of eliminating the threat from intentional use of

  9. Onychomycosis: Potential of Nail Lacquers in Transungual Delivery of Antifungals

    PubMed Central

    Sharma, Hemlata; Pathak, Kamla

    2016-01-01

    Onychomycosis constitutes the most common fungal infection of the nail (skin beneath the nail bed) that affects the finger as well as toe nails. It is an infection that is initiated by yeasts, dermatophytes, and nondermatophyte molds. Nail lacquers are topical solutions intended only for use on fingernails as well as toenails and have been found to be useful in the treatment of onychomycosis. Thus, in the present review an attempt has been made to focus on the treatment aspects of onychomycosis and the ungual delivery of antifungals via nail lacquer. Several patents issued on nail lacquer till date have also been discussed. Penetration efficiency was assessed by several researchers across the human nail plate to investigate the potentiality of nail lacquer based formulations. Various clinical trials have also been conducted in order to evaluate the safety and efficacy of nail lacquers in delivering antifungal agents. Thus, it can be concluded that nail lacquer based preparations are efficacious and stable formulations. These possess tremendous potential for clinical topical application to the nail bed in the treatment of onychomycosis. PMID:27123362

  10. Magnetic nanoparticles as gene delivery agents: enhanced transfection in the presence of oscillating magnet arrays

    NASA Astrophysics Data System (ADS)

    McBain, S. C.; Griesenbach, U.; Xenariou, S.; Keramane, A.; Batich, C. D.; Alton, E. W. F. W.; Dobson, J.

    2008-10-01

    Magnetic nanoparticle-based gene transfection has been shown to be effective in combination with both viral vectors and with non-viral agents. In these systems, therapeutic or reporter genes are attached to magnetic nanoparticles which are then focused to the target site/cells via high-field/high-gradient magnets. The technique has been shown to be efficient and rapid for in vitro transfection and compares well with cationic lipid-based reagents, producing good overall transfection levels with lower doses and shorter transfection times. In spite of its potential advantages (particularly for in vivo targeting), the overall transfection levels do not generally exceed those of other non-viral agents. In order to improve the overall transfection levels while maintaining the advantages inherent in this technique, we have developed a novel, oscillating magnet array system which adds lateral motion to the particle/gene complex in order to promote transfection. Experimental results indicate that the system significantly enhances overall in vitro transfection levels in human airway epithelial cells compared to both static field techniques (p<0.005) and the cationic lipids (p<0.001) tested. In addition, it has the previously demonstrated advantages of magnetofection—rapid transfection times and requiring lower levels of DNA than cationic lipid-based transfection agents. This method shows potential for non-viral gene delivery both in vitro and in vivo.

  11. Adhesive microbeads for the targeting delivery of anticaries agents of vegetable origin.

    PubMed

    Conti, Bice; Colzani, Barbara; Papetti, Adele; Mascherpa, Dora; Dorati, Rossella; Genta, Ida; Pruzzo, Carla; Signoretto, Caterina; Zaura, Edjia; Lingström, Peter; Ofek, Itzak; Wilson, Mike; Spratt, David A; Gazzani, Gabriella

    2013-06-01

    The formulation of quinic acid, a food constituent demonstrating potential anticaries and antigingivitis properties, was investigated in an adhesive microparticulate delivery system with the goal of improving its effect by prolonging its residence time at the site of action. Alginate and chitosan were selected as mucoadhesive polymers. The microspheres were prepared by coacervation. Different types of alginates, polymers blends and crosslinking agent concentrations were considered and evaluated. The best results in terms of encapsulation efficiency, in vitro active agent release profile and in vitro adhesive properties, both to oral mucosa and to teeth surface, were obtained with a blend of Alginate Protanal LF200S: Alginate Protanal LF120LS 1:1.5 w/w, 0.1M CaCl(2), and chitosan coating, prepared by a one-step complex coacervation method. This microparticulate delivery system showed prolonged release of quinic acid, and could be used as an active component in chewing gums or mouthwashes for both caries and gingivitis prevention. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. Plasma and cerebrospinal fluid pharmacokinetics of select chemotherapeutic agents following intranasal delivery in a non-human primate model.

    PubMed

    League-Pascual, James C; Lester-McCully, Cynthia M; Shandilya, Shaefali; Ronner, Lukas; Rodgers, Louis; Cruz, Rafael; Peer, Cody J; Figg, William D; Warren, Katherine E

    2017-03-13

    The blood-brain barrier (BBB) limits entry of most chemotherapeutic agents into the CNS, resulting in inadequate exposure within CNS tumor tissue. Intranasal administration is a proposed means of delivery that can bypass the BBB, potentially resulting in more effective chemotherapeutic exposure at the tumor site. The objective of this study was to evaluate the feasibility and pharmacokinetics (plasma and CSF) of intranasal delivery using select chemotherapeutic agents in a non-human primate (NHP) model. Three chemotherapeutic agents with known differences in CNS penetration were selected for intranasal administration in a NHP model to determine proof of principle of CNS delivery, assess tolerability and feasibility, and to evaluate whether certain drug characteristics were associated with increased CNS exposure. Intravenous (IV) temozolomide (TMZ), oral (PO) valproic acid, and PO perifosine were administered to adult male rhesus macaques. The animals received a single dose of each agent systemically and intranasally in separate experiments, with each animal acting as his own control. The dose of the agents administered systemically was the human equivalent of a clinically appropriate dose, while the intranasal dose was the maximum achievable dose based on the volume limitation of 1 mL. Multiple serial paired plasma and CSF samples were collected and quantified using a validated uHPLC/tandem mass spectrometry assay after each drug administration. Pharmacokinetic parameters were estimated using non-compartmental analysis. CSF penetration was calculated from the ratio of areas under the concentration-time curves for CSF and plasma (AUCCSF:plasma). Intranasal administration was feasible and tolerable for all agents with no significant toxicities observed. For TMZ, the degrees of CSF drug penetration after intranasal and IV administration were 36 (32-57) and 22 (20-41)%, respectively. Although maximum TMZ drug concentration in the CSF (Cmax) was lower after intranasal

  13. 78 FR 77471 - Prospective Grant of Exclusive License for: Convection Enhanced Delivery of a Therapeutic Agent...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-23

    ... therapeutic substances by MRI or CT that have been administered to tissue using convection enhanced delivery...-1992/0). The tracer is a molecule, detectable by MRI or CT, which functions as a surrogate for the... macromolecular MRI contrast agents such as chelated Gd(III). These macromolecular imaging agents have clearance...

  14. Targeted delivery of antibody-based therapeutic and imaging agents to CNS tumors: Crossing the blood-brain-barrier divide

    PubMed Central

    Chacko, Ann-Marie; Li, Chunsheng; Pryma, Daniel A.; Brem, Steven; Coukos, George; Muzykantov, Vladimir R.

    2014-01-01

    Introduction Brain tumors are inherently difficult to treat in large part due to the cellular blood-brain barriers (BBB) that limit the delivery of therapeutics to the tumor tissue from the systemic circulation. Virtually no large-molecules, including antibody-based proteins, can penetrate the BBB. With antibodies fast becoming attractive ligands for highly specific molecular targeting to tumor antigens, a variety of methods are being investigated to enhance the access of these agents to intracranial tumors for imaging or therapeutic applications. Areas covered This review describes the characteristics of the BBB and the vasculature in brain tumors, described as the blood-brain tumor barrier (BBTB). Antibodies targeted to molecular markers of CNS tumors will be highlighted, and current strategies for enhancing the delivery of antibodies across these cellular barriers into the brain parenchyma to the tumor will be discussed. Non-invasive imaging approaches to assess BBB/BBTB permeability and/or antibody targeting will be presented as a means of guiding the optimal delivery of targeted agents to brain tumors. Expert Opinion Pre-clinical and clinical studies highlight the potential of several approaches in increasing brain tumor delivery across the blood-brain barrier divide. However, each carries its own risks and challenges. There is tremendous potential in using neuroimaging strategies to assist in understanding and defining the challenges to translating and optimizing molecularly-targeted antibody delivery to CNS tumors to improve clinical outcomes. PMID:23751126

  15. Evaluation of unnatural cyclic amino acids as boron delivery agents for treatment of melanomas and gliomas.

    PubMed

    Barth, Rolf F; Kabalka, George W; Yang, Weilian; Huo, Tianyao; Nakkula, Robin J; Shaikh, Aarif L; Haider, Syed A; Chandra, Subhash

    2014-06-01

    Unnatural cyclic amino acids (UNAAs) are a new class of boron delivery agents that are in a pre-clinical stage of evaluation. In the present study, the biodistribution of racemic forms of the cis- and trans-isomers of the boronated UNAA 1-amino-3-boronocyclopentanecarboxylic acid (ABCPC) and 1-amino-3-boronocycloheptanecarboxylic acid (ABCHC) were evaluted in B16 melanoma bearing mice and this was compared to l-p-boronophenylalanine (BPA). Boron concentrations were determined by inductively coupled plasma-optical emission spectroscopy (ICP-OES) at 2.5h following intraperitoneal (i.p.) injection of the test agents at a concentration equivalent to 24mg/B/kg. While all compounds attained comparable tumor boron concentrations, the tumor/blood (T/Bl) boron concentration ratios were far superior for both cis-ABCPC and cis-ABCHC compared to BPA (T/Bl=16.4, and 15.1 vs. 5.4). Secondary ion mass spectrometry (SIMS) imaging revealed that the cis-ABCPC delivered boron to the nuclei, as well as the cytoplasm of B16 cells. Next, a biodistribution study of cis-ABCPC and BPA was carried out in F98 glioma bearing rats following i.p. administration. Both compounds attained comparable tumor boron concentrations but the tumor/brain (T/Br) boron ratio was superior for cis-ABCPC compared to BPA (6 vs. 3.3). Since UNAAs are water soluble and cannot be metabolized by tumor cells, they could be potentially more effective boron delivery agents than BPA. Our data suggest that further studies are warranted to evaluate these compounds prior to the initiation of clinical studies.

  16. Polymeric Microgels as Potential Drug Delivery Vesicles

    NASA Astrophysics Data System (ADS)

    McDonough, Ryan; Streletzky, Kiril; Bayachou, Mekki; Peiris, Pubudu

    2010-03-01

    The temperature dependent volume phase change of cross-linked amphiphilic molecules (microgels) suggests their use as drug delivery vesicles. Drug particles aggregate in the slightly hydrophobic microgel interior. They are stored in equilibrium until the critical temperature (Tv) is reached where the volume phase change limits available space, thus expelling the drugs. This loading property of hydroxypropylcellulose (HPC) microgels was tested using amperometric analytical techniques. Small molecules inside microgels do not approach the electrode surface, which decreases current signal. A room temperature (Troom) flow amperometric measurement comparing microgel/paracetamol solution with control paracetamol samples yielded about 20 percent concentration reduction in the microgel sample. Results from the steady-state electrochemical experiment confirm the 20 percent concentration drop in the microgel sample compared to the control sample at Troom. Using the steady-state experiment with a cyclic temperature ramp from Troom to beyond Tv showed that the paracetamol concentration change between the temperature extremes was greater for the microgels than for the controls. An evolving aspect of the study is the characterization of microgel shrinkage from in situ, temperature controlled liquid AFM images as compared to previously completed DLS characterization of the same microgel sample.

  17. Plasma Sterilization of Poly Lactic Acid Ultrasound Contrast Agents: Surface Modification and Implications for Drug Delivery

    PubMed Central

    Eisenbrey, John R.; Hsu, Jennifer; Wheatley, Margaret A.

    2013-01-01

    Poly lactic acid (PLA) ultrasound contrast agents (CA) have been previously developed in our laboratory for ultrasound (US) imaging, as well as surface coated with doxorubicin to create a potential targeted platform of chemotherapeutic delivery using focused US. However, we have previously found it impossible to sterilize these agents while at the same time maintaining their acoustic properties, a task that would probably require fabrication within a clean facility. The purpose of this paper is to investigate the feasibility of using plasma to sterilize these CA while maintaining maximum echogenicity, a step that would greatly facilitate in vivo investigations. Effects of plasma exposure time (1, 3 and 6 minutes) and intensity (low- 10 mA, 6.8 W; medium- 15 mA, 10.5 W; and high- 25 mA, 18W) on the CA’s acoustic properties, surface morphology, zeta potential, capacity to carry chemotherapeutics, and overall sterility are described. Both increases in plasma intensity and exposure time increased CA zeta potential and also significantly increased drug payload. High intensity plasma exposure for three minutes was found to be an optimal sterilization protocol for maximal (100%) preservation of CA echogenicity. Plasma exposure resulted in sterile samples and maintained original CA enhancement of 20 dB and acoustic half-life over 75 minutes, while increasing CA zeta potential by 11 mV and doxorubicin loading efficiency by 10%. This study not only shows how a highly temperature and pressure sensitive agent can be sterilized using plasma, but also that surface modification can be used to increase surface binding of drug. PMID:19766380

  18. A biomimetic hybrid nanoplatform for encapsulation and precisely controlled delivery of therasnostic agents

    PubMed Central

    Wang, Hai; Agarwal, Pranay; Zhao, Shuting; Yu, Jianhua; Lu, Xiongbin; He, Xiaoming

    2015-01-01

    Nanoparticles have demonstrated great potential for enhancing drug delivery. However, the low drug encapsulation efficiency at high drug-to-nanoparticle feeding ratios and minimal drug loading content in nanoparticle at any feeding ratios are major hurdles to their widespread applications. Here we report a robust eukaryotic cell-like hybrid nanoplatform (EukaCell) for encapsulation of theranostic agents (doxorubicin and indocyanine green). The EukaCell consists of a phospholipid membrane, a cytoskeleton-like mesoporous silica matrix and a nucleus-like fullerene core. At high drug-to-nanoparticle feeding ratios (for example, 1:0.5), the encapsulation efficiency and loading content can be improved by 58 and 21 times, respectively, compared with conventional silica nanoparticles. Moreover, release of the encapsulated drug can be precisely controlled via dosing near infrared laser irradiation. Ultimately, the ultra-high (up to ∼87%) loading content renders augmented anticancer capacity both in vitro and in vivo. Our EukaCell is valuable for drug delivery to fight against cancer and potentially other diseases. PMID:26621191

  19. A biomimetic hybrid nanoplatform for encapsulation and precisely controlled delivery of therasnostic agents

    NASA Astrophysics Data System (ADS)

    Wang, Hai; Agarwal, Pranay; Zhao, Shuting; Yu, Jianhua; Lu, Xiongbin; He, Xiaoming

    2015-12-01

    Nanoparticles have demonstrated great potential for enhancing drug delivery. However, the low drug encapsulation efficiency at high drug-to-nanoparticle feeding ratios and minimal drug loading content in nanoparticle at any feeding ratios are major hurdles to their widespread applications. Here we report a robust eukaryotic cell-like hybrid nanoplatform (EukaCell) for encapsulation of theranostic agents (doxorubicin and indocyanine green). The EukaCell consists of a phospholipid membrane, a cytoskeleton-like mesoporous silica matrix and a nucleus-like fullerene core. At high drug-to-nanoparticle feeding ratios (for example, 1:0.5), the encapsulation efficiency and loading content can be improved by 58 and 21 times, respectively, compared with conventional silica nanoparticles. Moreover, release of the encapsulated drug can be precisely controlled via dosing near infrared laser irradiation. Ultimately, the ultra-high (up to ~87%) loading content renders augmented anticancer capacity both in vitro and in vivo. Our EukaCell is valuable for drug delivery to fight against cancer and potentially other diseases.

  20. Hydrogels for Delivery of Bioactive Agents: A Historical Perspective

    PubMed Central

    Lee, Sang Cheon; Kwon, Il Keun; Park, Kinam

    2012-01-01

    Since 1960 when the history of modern hydrogels began significant progresses have been made in the field of controlled drug delivery. In particular, recent advances in the so-called smart hydrogels have made it possible to design highly sophisticated formulations, e.g., self-regulated drug delivery systems. Despite intensive efforts, clinical applications of smart hydrogels have been limited. Smart hydrogels need to be even smarter to execute functions necessary for achieving desired clinical functions. It is necessary to develop novel hydrogels that meet the requirements of the intended, specific applications, rather than finding applications of newly developed hydrogels. Furthermore, developing smarter hydrogels that can mimic natural systems is necessary, but the fundamental differences between natural and synthetic systems need to be understood. Such understanding will allow us to develop novel hydrogels with new, multiple functions we are looking for. PMID:22906864

  1. Nanomicellar carriers for targeted delivery of anticancer agents

    PubMed Central

    Zhang, Xiaolan; Huang, Yixian; Li, Song

    2014-01-01

    Clinical application of anticancer drugs is limited by problems such as low water solubility, lack of tissue-specificity and toxicity. Formulation development represents an important approach to these problems. Among the many delivery systems studied, polymeric micelles have gained considerable attention owing to ease in preparation, small sizes (10–100 nm), and ability to solubilize water-insoluble anticancer drugs and accumulate specifically at the tumors. This article provides a brief review of several promising micellar systems and their applications in tumor therapy. The emphasis is placed on the discussion of the authors’ recent work on several nanomicellar systems that have both a delivery function and antitumor activity, named dual-function drug carriers. PMID:24341817

  2. Core-shell-type magnetic mesoporous silica nanocomposites for bioimaging and therapeutic agent delivery.

    PubMed

    Wang, Yao; Gu, Hongchen

    2015-01-21

    Advances in nanotechnology and nanomedicine offer great opportunities for the development of nanoscaled theranostic platforms. Among various multifunctional nanocarriers, magnetic mesoporous silica nanocomposites (M-MSNs) attract prominent research interest for their outstanding properties and potential biomedical applications. This Research News article highlights recent progress in the design of core-shell-type M-MSNs for both diagnostic and therapeutic applications. First, an overview of synthetic strategies for three representative core-shell-type M-MSNs with different morphologies and structures is presented. Then, the diagnostic functions of M-MSNs is illustrated for magnetic resonance imaging (MRI) applications. Next, magnetic targeted delivery and stimuli-responsive release of drugs, and effective package of DNA/siRNA inside mesopores using M-MSNs as therapeutic agent carriers are discussed. The article concludes with some important challenges that need to be overcome for further practical applications of M-MSNs in nanomedicine.

  3. Dermal delivery by niosomes of black tea extract as a sunscreen agent.

    PubMed

    Yeh, Meng-I; Huang, Hsiu-Chin; Liaw, Jia-Horng; Huang, Min-Chuan; Huang, Kuei-Fen; Hsu, Feng-Lin

    2013-02-01

    The primary objective of this study was to investigate the feasibility of using niosomes as a delivery vehicle for the dermal administration in vitro of black tea extract (BTE) as a sunscreen. Multi-lamellar niosomes were obtained by means of a previously reported method of lipid hydration films. In vitro penetration experiments through nude mouse skin were carried out to evaluate the potential of niosomes as a dermal formulation. The nude mouse skin membrane allowed the effects of penetration with a niosome formulation to be evaluated. Penetration rates of caffeine- and gallic acid-loaded niosomes in a steady state were higher than dispersion in aqueous solutions. For skin permeation, higher transdermal absorption rates were seen with solutions of caffeine and gallic acid. In the near future, BTE as a sunscreen agent will be dermally delivered by niosomes. © 2012 The International Society of Dermatology.

  4. Carbon nanotubes: a potential concept for drug delivery applications.

    PubMed

    Kumar, Rakesh; Dhanawat, Meenakshi; Kumar, Sudhir; Singh, Brahma N; Pandit, Jayant K; Sinha, Vivek R

    2014-04-01

    The unique properties of carbon nanotubes (CNTs) make them a highly interesting and demandable nanocarrier in the field of nanoscience. CNTs facilitate efficient delivery of therapeutics like drugs, proteins, genes, nucleic acids, vitamins and lot more. Even though highly beneficial, the biocompatibility of CNTs is a major issue in their questioning their potential application in targeting drug delivery. Studies confirmed subdued toxicity of CNTs following slight modifications like functionalization, controlled dimensions, purification etc. A well-established mechanism for cellular internalization is an insistent need to attain a more efficient and targeted delivery. Recent patents have been thoroughly discussed in the text below.

  5. Keratin sponge/hydrogel II, active agent delivery

    USDA-ARS?s Scientific Manuscript database

    Keratin sponge/hydrogels from oxidation and reduction hydrolysis of fine and coarse wool fibers were formed to behave as cationic hydrogels to swell and release active agents in the specific region of the gastro-intestinal (GI) tract. Their porous, interpenetrating networks (IPN) were effective for...

  6. Intradermal delivery of vaccines: potential benefits and current challenges

    PubMed Central

    Hickling, JK; Jones, KR; Friede, M; Chen, D; Kristensen, D

    2011-01-01

    Abstract Delivery of vaccine antigens to the dermis and/or epidermis of human skin (i.e. intradermal delivery) might be more efficient than injection into the muscle or subcutaneous tissue, thereby reducing the volumes of antigen. This is known as dose-sparing and has been demonstrated in clinical trials with some, but not all, vaccines. Dose-sparing could be beneficial to immunization programmes by potentially reducing the costs of purchase, distribution and storage of vaccines; increasing vaccine availability and effectiveness. The data obtained with intradermal delivery of some vaccines are encouraging and warrant further study and development; however significant gaps in knowledge and operational challenges such as reformulation, optimizing vaccine presentation and development of novel devices to aid intradermal vaccine delivery need to be addressed. Modelling of the costs and potential savings resulting from intradermal delivery should be done to provide realistic expectations of the potential benefits and to support cases for investment. Implementation and uptake of intradermal vaccine delivery requires further research and development, which depends upon collaboration between multiple stakeholders in the field of vaccination. PMID:21379418

  7. Intradermal delivery of vaccines: potential benefits and current challenges.

    PubMed

    Hickling, J K; Jones, K R; Friede, M; Zehrung, D; Chen, D; Kristensen, D

    2011-03-01

    Delivery of vaccine antigens to the dermis and/or epidermis of human skin (i.e. intradermal delivery) might be more efficient than injection into the muscle or subcutaneous tissue, thereby reducing the volumes of antigen. This is known as dose-sparing and has been demonstrated in clinical trials with some, but not all, vaccines. Dose-sparing could be beneficial to immunization programmes by potentially reducing the costs of purchase, distribution and storage of vaccines; increasing vaccine availability and effectiveness. The data obtained with intradermal delivery of some vaccines are encouraging and warrant further study and development; however significant gaps in knowledge and operational challenges such as reformulation, optimizing vaccine presentation and development of novel devices to aid intradermal vaccine delivery need to be addressed. Modelling of the costs and potential savings resulting from intradermal delivery should be done to provide realistic expectations of the potential benefits and to support cases for investment. Implementation and uptake of intradermal vaccine delivery requires further research and development, which depends upon collaboration between multiple stakeholders in the field of vaccination.

  8. Potential of nanoparticulate drug delivery systems by intranasal administration.

    PubMed

    Ali, Javed; Ali, Mushir; Baboota, Sanjula; Sahani, Jasjeet Kaur; Ramassamy, Charles; Dao, Lé; Bhavna

    2010-05-01

    Due to number of problems related with oral, parenteral, rectal and other routes of drug administration, the interest of pharmaceutical scientists has increased towards exploring the possibilities of intranasal delivery of various drugs. Nasal drug delivery system is commonly known for the treatment of local ailments like cold, cough, rhinitis, etc. Efforts have been made to deliver various drugs, especially peptides and proteins, through nasal route for systemic use; utilizing the principles and concepts of various nanoparticulate drug delivery systems using various polymers and absorption promoters. The incorporation of drugs into nanoparticles might be a promising approach, since colloidal formulations have been shown to protect them from the degrading milieu in the nasal cavity and facilitate their transport across the mucosal barriers. The use of nanoparticles for vaccine delivery provides beneficial effect, by achieving good immune responses. This could be due to the fact that small particles can be transported preferentially by the lymphoid tissue of the nasal cavity (NALT). The brain gets benefited through the intranasal delivery as direct olfactory transport bypasses the blood brain barrier and nanoparticles are taken up and conveyed along cell processes of olfactory neurons through the cribriform plate to synaptic junctions with neurons of the olfactory bulb. The intranasal delivery is aimed at optimizing drug bioavailability for systemic drugs, as absorption decreases with increasing molecular weight, and for drugs, which are susceptible to enzymatic degradation such as proteins and polypeptides. This review discusses the potential benefits of using nanoparticles for nasal delivery of drugs and vaccines for brain, systemic and topical delivery. The article aims at giving an insight into nasal cavity, consideration of factors affecting and strategies to improve drug absorption through nasal route, pharmaceutical dosage forms and delivery systems with

  9. Radioiodinated carnitine and acylcarnitine analogs as potential myocardial imaging agents

    SciTech Connect

    McConnell, D.S.

    1991-01-01

    R-carnitine is extremely important in mammalian energy metabolism. Gamma-butyrobetaine, the immediate biosynthetic precursor to R-carnitine, is synthesized in many organs. However, only liver can hydroxylate gamma-butyrobetaine to carnitine. Thus the transport of carnitine from its site of synthesis to the site of utilization is of utmost importance. Carnitine is found in highest concentration in cardiac and skeletal muscle, where it is required for the transport of fatty acids into the mitochondria. Before fatty acids are utilized as fuel for the myocyte by beta-oxidation, they are bound to carnitine as an acylcarnitine ester at the 3-hydroxyl, and transported across the micochondrial membranes. R,S-Carnitine has been shown to be taken up by myocytes. The author has begun a study on the use of carnitine derivatives as potential carriers for the site-specific delivery of radioiodine to bidning sites in the myocardium. Such agents labeled with a gamma-emitting nuclide such as iodine-123 would be useful for the noninvasive imaging of these tissues. The aim was to synthesize a variety of radiolabeled analogs of carnitine and acylcarnitine to address questions of transport, binding and availability for myocardial metabolism. These analogs consist of N-alkylated derivatives of carnitine, acylcarnitine esters as well as carnitine amides and ethers. One C-alkylated derivative showed interesting biodistribution, elevated myocardial uptake and competition with carnitine for binding in the myocardium.

  10. Nanocarrier-mediated co-delivery of chemotherapeutic drugs and gene agents for cancer treatment.

    PubMed

    Kang, Lin; Gao, Zhonggao; Huang, Wei; Jin, Mingji; Wang, Qiming

    2015-05-01

    The efficacy of chemotherapeutic drug in cancer treatment is often hampered by drug resistance of tumor cells, which is usually caused by abnormal gene expression. RNA interference mediated by siRNA and miRNA can selectively knock down the carcinogenic genes by targeting specific mRNAs. Therefore, combining chemotherapeutic drugs with gene agents could be a promising strategy for cancer therapy. Due to poor stability and solubility associated with gene agents and drugs, suitable protective carriers are needed and have been widely researched for the co-delivery. In this review, we summarize the most commonly used nanocarriers for co-delivery of chemotherapeutic drugs and gene agents, as well as the advances in co-delivery systems.

  11. Polylactide-co-glycolide nanoparticles for controlled delivery of anticancer agents

    PubMed Central

    Dinarvand, R; Sepehri, N; Manoochehri, S; Rouhani, H; Atyabi, F

    2011-01-01

    The effectiveness of anticancer agents may be hindered by low solubility in water, poor permeability, and high efflux from cells. Nanomaterials have been used to enable drug delivery with lower toxicity to healthy cells and enhanced drug delivery to tumor cells. Different nanoparticles have been developed using different polymers with or without surface modification to target tumor cells both passively and/or actively. Polylactide-co-glycolide (PLGA), a biodegradable polyester approved for human use, has been used extensively. Here we report on recent developments concerning PLGA nanoparticles prepared for cancer treatment. We review the methods used for the preparation and characterization of PLGA nanoparticles and their applications in the delivery of a number of active agents. Increasing experience in the field of preparation, characterization, and in vivo application of PLGA nanoparticles has provided the necessary momentum for promising future use of these agents in cancer treatment, with higher efficacy and fewer side effects. PMID:21720501

  12. Nanocarrier-mediated co-delivery of chemotherapeutic drugs and gene agents for cancer treatment

    PubMed Central

    Kang, Lin; Gao, Zhonggao; Huang, Wei; Jin, Mingji; Wang, Qiming

    2015-01-01

    The efficacy of chemotherapeutic drug in cancer treatment is often hampered by drug resistance of tumor cells, which is usually caused by abnormal gene expression. RNA interference mediated by siRNA and miRNA can selectively knock down the carcinogenic genes by targeting specific mRNAs. Therefore, combining chemotherapeutic drugs with gene agents could be a promising strategy for cancer therapy. Due to poor stability and solubility associated with gene agents and drugs, suitable protective carriers are needed and have been widely researched for the co-delivery. In this review, we summarize the most commonly used nanocarriers for co-delivery of chemotherapeutic drugs and gene agents, as well as the advances in co-delivery systems. PMID:26579443

  13. ADVANCED MOLECULAR DESIGN OF BIOPOLYMERS FOR TRANSMUCOSAL AND INTRACELLULAR DELIVERY OF CHEMOTHERAPEUTIC AGENTS AND BIOLOGICAL THERAPEUTICS

    PubMed Central

    Liechty, William B.; Caldorera-Moore, Mary; Phillips, Margaret A.; Schoener, Cody; Peppas, Nicholas A.

    2011-01-01

    Hydrogels have been instrumental in the development of polymeric systems for controlled release of therapeutic agents. These materials are attractive for transmucosal and intracellular drug delivery because of their facile synthesis, inherent biocompatibility, tunable physicochemical properties, and capacity to respond to various physiological stimuli. In this contribution, we outline a multifaceted hydrogel-based approach for expanding the range of therapeutics in oral formulations from classical small-molecule drugs to include proteins, chemotherapeutics, and nucleic acids. Through judicious materials selection and careful design of copolymer composition and molecular architecture, we can engineer systems capable of responding to distinct physiological cues, with tunable physicochemical properties that are optimized to load, protect, and deliver valuable macromolecular payloads to their intended site of action. These hydrogel carriers, including complexation hydrogels, tethered hydrogels, interpenetrating networks, nanoscale hydrogels, and hydrogels with decorated structures are investigated for their ability respond to changes in pH, to load and release insulin and fluorescein, and remain non-toxic to Caco-2 cells. Our results suggest these novel hydrogel networks have great potential for controlled delivery of proteins, chemotherapeutics, and nucleic acids. PMID:21699934

  14. Novel Cholesterol-Based Cationic Lipids as Transfecting Agents of DNA for Efficient Gene Delivery

    PubMed Central

    Ju, Jia; Huan, Meng-Lei; Wan, Ning; Qiu, Hai; Zhou, Si-Yuan; Zhang, Bang-Le

    2015-01-01

    The design, synthesis and biological evaluation of the cationic lipid gene delivery vectors based on cholesterol and natural amino acids lysine or histidine are described. Cationic liposomes composed of the newly synthesized cationic lipids 1a or 1b and neutral lipid DOPE (1,2-dioleoyl-l-α-glycero-3-phosphatidyl-ethanolamine) exhibited good transfection efficiency. pEGFP-N1 plasmid DNA was transferred into 293T cells by cationic liposomes formed from cationic lipids 1a and 1b, and the transfection activity of the cationic lipids was superior (1a) or parallel (1b) to that of the commercially available 3β-[N-(N',N'-dimethylaminoethyl)-carbamoyl] cholesterol (DC-Chol) derived from the same cholesterol backbone with different head groups. Combined with the results of agarose gel electrophoresis, transfection experiments with various molar ratios of the cationic lipids and DOPE and N/P (+/−) molar charge ratios, a more effective formulation was formed, which could lead to relatively high transfection efficiency. Cationic lipid 1a represents a potential agent for the liposome used in gene delivery due to low cytotoxicity and impressive gene transfection activity. PMID:25768346

  15. Novel cholesterol-based cationic lipids as transfecting agents of DNA for efficient gene delivery.

    PubMed

    Ju, Jia; Huan, Meng-Lei; Wan, Ning; Qiu, Hai; Zhou, Si-Yuan; Zhang, Bang-Le

    2015-03-11

    The design, synthesis and biological evaluation of the cationic lipid gene delivery vectors based on cholesterol and natural amino acids lysine or histidine are described. Cationic liposomes composed of the newly synthesized cationic lipids 1a or 1b and neutral lipid DOPE (1,2-dioleoyl-L-α-glycero-3-phosphatidyl-ethanolamine) exhibited good transfection efficiency. pEGFP-N1 plasmid DNA was transferred into 293T cells by cationic liposomes formed from cationic lipids 1a and 1b, and the transfection activity of the cationic lipids was superior (1a) or parallel (1b) to that of the commercially available 3β-[N-(N',N'-dimethylaminoethyl)-carbamoyl] cholesterol (DC-Chol) derived from the same cholesterol backbone with different head groups. Combined with the results of agarose gel electrophoresis, transfection experiments with various molar ratios of the cationic lipids and DOPE and N/P (+/-) molar charge ratios, a more effective formulation was formed, which could lead to relatively high transfection efficiency. Cationic lipid 1a represents a potential agent for the liposome used in gene delivery due to low cytotoxicity and impressive gene transfection activity.

  16. Sonophoresis using ultrasound contrast agents for transdermal drug delivery: an in vivo experimental study.

    PubMed

    Park, Donghee; Ryu, Heungil; Kim, Han Sung; Kim, Young-Sun; Choi, Kyu-Sil; Park, Hyunjin; Seo, Jongbum

    2012-04-01

    Sonophoresis temporally increases skin permeability such that various medications can be delivered noninvasively. Previous sonophoresis studies have suggested that cavitation plays an important role in enhancing transdermal drug delivery (TDD). In this study, the feasibility of controlled cavitation using ultrasound contrast agents (UCAs) at high frequency was explored through in vivo experiments in a rat model. Two commercially available UCAs, SonoVue® and Definity®, were used at 2.47 MHz and 1.12 MHz, respectively. Fluorescein isothiocyanate (FITC)-dextran with 0.1% UCA was used as the drug to be delivered through the skin. Ultrasound with a 10 ms pulse and a 1% duty cycle at 1 MPa acoustic pressure for 30 min was applied in all sonication sessions. The efficacy of sonophoresis with UCAs was quantitatively analyzed using an optical imaging system that was used to count photons emitted from fluorescein. The results showed that the proposed sonophoresis method significantly improved drug penetration compared with the traditional sonophoresis method with 4 kD, 20 kD and 150 kD FITC-dextrans at 1.12 MHz, and with 4 kD and 20 kD FITC-dextrans at 2.47 MHz. Sonophoresis for TDD was performed more effectively with the aid of UCAs. Sonophoresis with UCAs has excellent potential for broad applications in drug delivery for diseases requiring the chronic administration of medications such as diabetes.

  17. Enhancement of transepidermal skin clearing agent delivery using a 980 nm diode laser.

    PubMed

    Stumpp, O F; Welch, A J; Milner, T E; Neev, J

    2005-10-01

    Patient compliant optical skin clearing requires non-invasive topical delivery of clearing agents such as glycerol. This requires reducing the skin barrier function by disrupting stratum corneum integrity, which was achieved using a 980 nm diode laser with artificial absorption substrates on the skin surface. Reduction of light scattering has the potential to improve many current and novel diagnostic and therapeutic applications of lasers in medicine. In vivo hamster and rat skin was used to test optical skin clearing. Absorption substrates were applied to the skin after shaving. These included black ink, dark children's rub-on tattoo, and carbon paper. 980 nm cw laser light was used to ablate these substrates and to heat the skin surface to enhance the diffusion of topically applied glycerol for optical skin clearing. Increased light penetration was determined from amplitude optical coherence tomography data. Results indicate an improvement of the ability to measure an OCT signal at a wavelength of 1,290 nm up to 42% deeper into in vivo rodent skin using a 980 nm laser with a fluence of less than 0.96 J/mm(2) to alter the stratum corneum. The use of an inexpensive diode laser can significantly enhance the delivery of topically applied glycerol for optical skin clearing. The laser use involves application of an absorption substrate onto the skin surface. Using carbon paper left no unwanted residue behind and is considered optimal for this purpose.

  18. Transferrin receptors and the targeted delivery of therapeutic agents against cancer

    PubMed Central

    Daniels, Tracy R.; Bernabeu, Ezequiel; Rodríguez, José A.; Patel, Shabnum; Kozman, Maggie; Chiappetta, Diego A.; Holler, Eggehard; Ljubimova, Julia Y.; Helguera, Gustavo; Penichet, Manuel L.

    2012-01-01

    Background Traditional cancer therapy can be successful in destroying tumors, but can also cause dangerous side effects. Therefore, many targeted therapies are in development. The transferrin receptor (TfR) functions in cellular iron uptake through its interaction with transferrin. This receptor is an attractive molecule for the targeted therapy of cancer since it is upregulated on the surface of many cancer types and is efficiently internalized. This receptor can be targeted in two ways: 1) for the delivery of therapeutic molecules into malignant cells or 2) to block the natural function of the receptor leading directly to cancer cell death. Scope of review In the present article we discuss the strategies used to target the TfR for the delivery of therapeutic agents into cancer cells. We provide a summary of the vast types of anti-cancer drugs that have been delivered into cancer cells employing a variety of receptor binding molecules including Tf, anti-TfR antibodies, or TfR-binding peptides alone or in combination with carrier molecules including nanoparticles and viruses. Major conclusions Targeting the TfR has been shown to be effective in delivering many different therapeutic agents and causing cytotoxic effects in cancer cells in vitro and in vivo. General significance The extensive use of TfR for targeted therapy attests to the versatility of targeting this receptor for therapeutic purposes against malignant cells. More advances in this area are expected to further improve the therapeutic potential of targeting the TfR for cancer therapy leading to an increase in the number of clinical trials of molecules targeting this receptor. PMID:21851850

  19. Molecular Diagnostic and Drug Delivery Agents based on Aptamer-Nanomaterial Conjugates

    PubMed Central

    Lee, Jung Heon; Yigit, Mehmet V.; Mazumdar, Debapriya; Lu, Yi

    2010-01-01

    Recent progress in an emerging area of designing aptamer and nanomaterial conjugates as molecular diagnostic and drug delivery agents in biomedical applications is summarized. Aptamers specific for a wide range of targets are first introduced and compared to antibodies. Methods of integrating these aptamers with a variety of nanomaterials, such as gold nanoparticles, quantum dots, carbon nanotubes, and superparamagnetic iron oxide nanoparticles, each with unique optical, magnetic, and electrochemical properties, are reviewed. Applications of these systems as fluorescent, colorimetric, magnetic resonance imaging, and electrochemical sensors in medical diagnostics are given, along with new applications as smart drug delivery agents. PMID:20338204

  20. Molecular diagnostic and drug delivery agents based on aptamer-nanomaterial conjugates.

    PubMed

    Lee, Jung Heon; Yigit, Mehmet V; Mazumdar, Debapriya; Lu, Yi

    2010-04-30

    Recent progress in an emerging area of designing aptamer and nanomaterial conjugates as molecular diagnostic and drug delivery agents in biomedical applications is summarized. Aptamers specific for a wide range of targets are first introduced and compared to antibodies. Methods of integrating these aptamers with a variety of nanomaterials, such as gold nanoparticles, quantum dots, carbon nanotubes, and superparamagnetic iron oxide nanoparticles, each with unique optical, magnetic, and electrochemical properties, are reviewed. Applications of these systems as fluorescent, colorimetric, magnetic resonance imaging, and electrochemical sensors in medical diagnostics are given, along with new applications as smart drug delivery agents.

  1. Seeking better topical delivery technologies of moisturizing agents for enhanced skin moisturization.

    PubMed

    Kim, Hyeongmin; Kim, Jeong Tae; Barua, Sonia; Yoo, Seung-Yup; Hong, Seong-Chul; Lee, Kyung Bin; Lee, Jaehwi

    2017-03-20

    An adequate hydration level is essential to maintain epidermal barrier functions and normal physiological activities of skin tissues. Diverse moisturizing agents and pharmaceutical formulations for dermal deliveries have thus extensively been investigated. This review comprehensively discusses scientific outcomes of moisturizing agents and pharmaceutical vehicles for skin moisturization, thereby providing insight into designing innovative pharmaceutical formulations for effective skin moisturization. Areas covered: We discussed the functions of various moisturizing agents ranging from conventional creams to novel moisturizers which has recently been explored. In addition, novel pharmaceutical formulations for efficient dermal delivery of the moisturizers, in particular, nanocarriers, were discussed along with their uses in commercial products. Expert opinion: Although various moisturizing agents have demonstrated their promising effects, exploitation of pharmaceutical formulations for their dermal delivery have been limited to few commonly used moisturizing agents. Thus, combinatorial investigation of novel moisturizers and pharmaceutical vehicles should be further conducted. As a new concept for improving skin moisturization, skin regeneration technologies using therapeutic cells have recently shown great promise for skin moisturization, but major challenges remain, such as efficient delivery and prolonged survival of such cells. Thus, novel approaches for improving skin moisturization require continuous efforts of pharmaceutical scientists to address the remaining problems.

  2. Bypassing the blood-brain barrier: delivery of therapeutic agents by macrophages

    NASA Astrophysics Data System (ADS)

    Hirschberg, Henry; Baek, Seung-Kuk; Kwon, Young Jik; Sun, Chung-Ho; Madsen, Steen J.

    2010-02-01

    Introduction: Failure to eradicate infiltrating glioma cells using conventional treatment regimens results in tumor recurrence and is responsible for the dismal prognosis of patients with glioblastoma multiforme (GBM). This is due to the fact that these migratory cells are protected by the blood-brain barrier (BBB) and the blood brain tumor barrier (BBTB) which prevents the delivery of most anti-cancer agents. We have evaluated the ability of monocytes/macrophages (Mo/Ma) to cross the BBB in rats. This will permit access of anti-cancer agents such as nanoparticles to effectively target the infiltrating tumor cells, and potentially improve the treatment effectiveness for malignant gliomas. Materials and Methods: The infiltration of Mo/Ma into brain tumor spheroids in vitro was determined using fluorescent stained Mo/Ma. Tumors were also established in the brains of inbred rats and ALA-PDT was given 18 days following tumor induction. The degredation of the BBTB and quantification of the number of infiltrating Mo/Ma was examined on histological sections from removed brains. Results & Conclusion: PDT was highly effective in locally opening the BBTB and inducing macrophage migration into the irradiated portions of brain tumors.

  3. A feeding protocol for delivery of agents to assess development in Varroa mites

    USDA-ARS?s Scientific Manuscript database

    A novel feeding protocol for delivery of bio-active agents to Varroa mites was developed by providing mites with honey bee larva hemolymph supplemented with cultured insect cells and selected materials suspended delivered on a fibrous cotton substrate. Mites were starved, fed on treated hemolymph to...

  4. Efficient synthesis of benzamide riboside, a potential anticancer agent.

    PubMed

    Bonnac, Laurent F; Gao, Guang-Yao; Chen, Liqiang; Patterson, Steven E; Jayaram, Hiremagalur N; Pankiewicz, Krzysztof W

    2007-01-01

    An efficient five step synthesis of benzamide riboside (BR) amenable for a large scale synthesis has been developed. It allows for extensive pre-clinical studies of BR as a potential anticancer agent.

  5. Rhizoma Coptidis: A Potential Cardiovascular Protective Agent

    PubMed Central

    Tan, Hui-Li; Chan, Kok-Gan; Pusparajah, Priyia; Duangjai, Acharaporn; Saokaew, Surasak; Mehmood Khan, Tahir; Lee, Learn-Han; Goh, Bey-Hing

    2016-01-01

    Cardiovascular diseases (CVDs) are among the leading causes of morbidity and mortality in both the developed and developing world. Rhizoma coptidis (RC), known as Huang Lian in China, is the dried rhizome of medicinal plants from the family Ranunculaceae, such as Coptis chinensis Franch, C. deltoidea C.Y. Cheng et Hsiao, and C. teeta Wall which has been used by Chinese medicinal physicians for more than 2000 years. In China, RC is a common component in traditional medicines used to treat CVD associated problems including obesity, diabetes mellitus, hyperlipidemia, hyperglycemia and disorders of lipid metabolism. In recent years, numerous scientific studies have sought to investigate the biological properties of RC to provide scientific evidence for its traditional medical uses. RC has been found to exert significant beneficial effects on major risk factors for CVDs including anti-atherosclerotic effect, lipid-lowering effect, anti-obesity effect and anti-hepatic steatosis effect. It also has myocardioprotective effect as it provides protection from myocardial ischemia-reperfusion injury. These properties have been attributed to the presence of bioactive compounds contained in RC such as berberine, coptisine, palmatine, epiberberine, jatrorrhizine, and magnoflorine; all of which have been demonstrated to have cardioprotective effects on the various parameters contributing to the occurrence of CVD through a variety of pathways. The evidence available in the published literature indicates that RC is a herb with tremendous potential to reduce the risks of CVDs, and this review aims to summarize the cardioprotective properties of RC with reference to the published literature which overall indicates that RC is a herb with remarkable potential to reduce the risks and damage caused by CVDs. PMID:27774066

  6. Multiplexed and Switchable Release of Distinct Fluids from Microneedle Platforms via Conducting Polymer Nanoactuators for Potential Drug Delivery

    PubMed Central

    Valdés-Ramírez, Gabriela; Windmiller, Joshua R.; Claussen, Jonathan C.; Martinez, Alexandra G.; Kuralay, Filiz; Zhou, Ming; Zhou, Nandi; Polsky, Ronen; Miller, Philip R.; Narayan, Roger; Wang, Joseph

    2013-01-01

    We report on the development of a microneedle-based multiplexed drug delivery actuator that enables the controlled delivery of multiple therapeutic agents. Two individually-addressable channels on a single microneedle array, each paired with its own reservoir and conducting polymer nanoactuator, are used to deliver various permutations of two unique chemical species. Upon application of suitable redox potentials to the selected actuator, the conducting polymer is able to undergo reversible volume changes, thereby serving to release a model chemical agent in a controlled fashion through the corresponding microneedle channels. Time-lapse videos offer direct visualization and characterization of the membrane switching capability and, along with calibration investigations, confirm the ability of the device to alternate the delivery of multiple reagents from individual microneedles of the array with higher precision and temporal resolution than conventional drug delivery actuators. Analytical modeling offers prediction of the volumetric flow rate through a single microneedle and accordingly can be used to assist in the design of subsequent microneedle arrays. The robust solid-state design and lack of mechanical components circumvent reliability issues that challenge fragile conventional microelectromechanical drug delivery devices. This proof-of-concept study demonstrates the potential of the drug delivery actuator system to aid in the rapid administration of multiple therapeutic agents and indicates the potential to counteract diverse biomedical conditions. PMID:24174709

  7. Multiplexed and Switchable Release of Distinct Fluids from Microneedle Platforms via Conducting Polymer Nanoactuators for Potential Drug Delivery.

    PubMed

    Valdés-Ramírez, Gabriela; Windmiller, Joshua R; Claussen, Jonathan C; Martinez, Alexandra G; Kuralay, Filiz; Zhou, Ming; Zhou, Nandi; Polsky, Ronen; Miller, Philip R; Narayan, Roger; Wang, Joseph

    2012-01-03

    We report on the development of a microneedle-based multiplexed drug delivery actuator that enables the controlled delivery of multiple therapeutic agents. Two individually-addressable channels on a single microneedle array, each paired with its own reservoir and conducting polymer nanoactuator, are used to deliver various permutations of two unique chemical species. Upon application of suitable redox potentials to the selected actuator, the conducting polymer is able to undergo reversible volume changes, thereby serving to release a model chemical agent in a controlled fashion through the corresponding microneedle channels. Time-lapse videos offer direct visualization and characterization of the membrane switching capability and, along with calibration investigations, confirm the ability of the device to alternate the delivery of multiple reagents from individual microneedles of the array with higher precision and temporal resolution than conventional drug delivery actuators. Analytical modeling offers prediction of the volumetric flow rate through a single microneedle and accordingly can be used to assist in the design of subsequent microneedle arrays. The robust solid-state design and lack of mechanical components circumvent reliability issues that challenge fragile conventional microelectromechanical drug delivery devices. This proof-of-concept study demonstrates the potential of the drug delivery actuator system to aid in the rapid administration of multiple therapeutic agents and indicates the potential to counteract diverse biomedical conditions.

  8. Efficient Percutaneous Delivery of the Antimelanogenic Agent Glabridin Using Cationic Amphiphilic Chitosan Micelles

    PubMed Central

    Seino, Haruyoshi; Arai, Yukari; Nagao, Norio; Ozawa, Noriyasu; Hamada, Kazuhiko

    2016-01-01

    Partially myristoylated chitosan pyrrolidone carboxylate (PMCP) is a cationic amphiphilic chitosan derivative. Glabridin (Glab) from licorice root extracts is a hydrophobic antimelanogenic agent. Here we assessed the effects of cationic Glab-containing polymeric micelles derived from PMCP (Glab/PMCP-PM) on the ability of Glab to penetrate the skin and inhibit melanogenesis using a human skin model. The amount of Glab absorbed 24 h after the application of Glab/PMCP-PM was approximately four times higher than that of conventional oil-in-water micelles (control) prepared using Tween 60. Further, the release of IL-1α, a mediator of inflammation, was not detected. Treatment with Glab/PMCP-PM significantly increased the inhibition of melanogenesis compared with control. The inhibition of melanogenesis depends upon the enhanced ability of Glab to penetrate the skin, particularly the epidermis. Moreover, the inhibition of melanogenesis and the cationic potential of the Glab/PMCP-PM levels were increased by the cationic phospholipid copolymer. Therefore, Glab/PMCP-PM shows potential as an effective transdermal delivery system for treating skin hyperpigmentation. PMID:27695112

  9. Microbubble contrast agents: targeted ultrasound imaging and ultrasound-assisted drug-delivery applications.

    PubMed

    Klibanov, Alexander L

    2006-03-01

    The use of microbubble contrast agents for general tissue delineation and perfusion enjoys steady interest in ultrasound imaging. Microbubbles as contrast materials require a small dosage and show excellent detection sensitivity. Targeting ligands on the surface of microbubbles permit the selective accumulation of these particles in the areas of interest, which show an up-regulated level of receptor molecules on vascular endothelium. Selective contrast imaging of inflammation, ischemia-reperfusion injury, angiogenesis, and thrombosis has been achieved in animal models. Ultrasound-assisted drug delivery and activation, performed by combining microbubble agent containing drug substances or coadministered with pharmaceutical agents (including plasmid DNA for transfection), has been achieved in multiple model systems in vitro and in vivo. Ultrasound and microbubbles-based targeted acceleration of the thrombolytic enzyme action already have reached clinical trials. Overall, microbubble targeting and ultrasound-assisted microbubble-based drug-delivery systems will offer a step toward the application of targeted personalized diagnostics and therapy.

  10. Alk5 inhibition increases delivery of macromolecular and protein-bound contrast agents to tumors

    PubMed Central

    Daldrup-Link, Heike E.; Mohanty, Suchismita; Ansari, Celina; Ito, Ken; Hong, Su Hyun; Hoffmann, Matthias; Pisani, Laura; Boudreau, Nancy; Gambhir, Sanjiv Sam; Coussens, Lisa M.

    2016-01-01

    Limited transendothelial permeability across tumor microvessels represents a significant bottleneck in the development of tumor-specific diagnostic agents and theranostic drugs. Here, we show an approach to increase transendothelial permeability of macromolecular and nanoparticle-based contrast agents via inhibition of the type I TGF-β receptor, activin-like kinase 5 (Alk5), in tumors. Alk5 inhibition significantly increased tumor contrast agent delivery and enhancement on imaging studies, while healthy organs remained relatively unaffected. Imaging data correlated with significantly decreased tumor interstitial fluid pressure, while tumor vascular density remained unchanged. This immediately clinically translatable concept involving Alk5 inhibitor pretreatment prior to an imaging study could be leveraged for improved tumor delivery of macromolecular and nanoparticle-based imaging probes and, thereby, facilitate development of more sensitive imaging tests for cancer diagnosis, enhanced tumor characterization, and personalized, image-guided therapies. PMID:27182558

  11. Medicated chewing gum--a potential drug delivery system.

    PubMed

    Chaudhary, Shivang A; Shahiwala, Aliasgar F

    2010-07-01

    Over the years, patient convenience and patient compliance-orientated research in the field of drug delivery has resulted in bringing out potential innovative drug delivery options. Out of which, medicated chewing gum (MCG) offers a highly convenient patient-compliant way of dosing medications, not only for special population groups with swallowing difficulties such as children and the elderly, but also for the general population, including the young generation. In this review, various formulation ingredients, different manufacturing processes, and assessment of in vivo and in vitro drug release from MCG are thoroughly discussed along with the therapeutic potential and limitations of MCG. Readers will gain knowledge about the rationale and prominent formulation and performance evaluation strategies behind chewing gum as a drug delivery system. The availability of directly compressible co-processed gum material enables rapid, safe and low-cost development of MCG as a drug delivery option. By MCG formulation, revitalization of old products and reformulation of new patented products is possible, to differentiate them from upcoming generics competition in the market.

  12. Potential Use of Alginate-Based Carriers As Antifungal Delivery System

    PubMed Central

    Spadari, Cristina de Castro; Lopes, Luciana B.; Ishida, Kelly

    2017-01-01

    Fungal infections have become a major public health problem, growing in number and severity in recent decades due to an increase of immunocompromised patients. The use of therapeutic agents available to treat these fungal infections is limited by their toxicity, low bioavailability, antifungal resistance, and high cost of treatment. Thus, it becomes extremely important to search for new therapeutic options. The use of polymeric systems as drug carriers has emerged as a promising alternative to conventional formulations for antifungals. Alginate is a natural polymer that has been explored in the last decade for development of drug delivery systems due to its non-toxicity, biodegradability, biocompatibility, low cost, mucoadhesive, and non-immunogenic properties. Several antifungal agents have been incorporated in alginate-based delivery systems, including micro and nanoparticles, with great success, displaying promising in vitro and in vivo results for antifungal activities, reduction in the toxicity and the total drug dose used in the treatment, and improved bioavailability. This review aims at discussing the potential use and benefits of alginate-based nanocarriers and other delivery systems containing antifungal agents in the therapy of fungal infections. PMID:28194145

  13. Effect of functionalization on drug delivery potential of carbon nanotubes.

    PubMed

    Sharma, Sonam; Mehra, Neelesh Kumar; Jain, Keerti; Jain, Narendra Kumar

    2016-12-01

    The main aim of the present investigation was to explore the effect of functionalization on drug delivery potential of carbon nanotubes (CNTs) and to compare the in vitro and in vivo cancer targeting potential of doxorubicin HCL (DOX)-loaded ox-/multi-walled CNTs (MWCNTs), DOX-loaded PEG-MWCNTs and DOX-loaded FA-PEG-MWCNTs. The DOX/PEG-FA-MWCNTs showed enhanced cytotoxicity and were most preferentially taken up by the cancerous cells. The obtained results also support the extended resistance time and sustained release profile of drug-loaded surface-engineered MWCNTs. Overall, we concluded that the developed MWCNTs nanoformulations have higher cancer targeting potential.

  14. Fluorine-Containing Taxoid Anticancer Agents and Their Tumor-Targeted Drug Delivery

    PubMed Central

    Seitz, Joshua; Vineberg, Jacob G.; Zuniga, Edison S.; Ojima, Iwao

    2013-01-01

    A long-standing problem of conventional chemotherapy is the lack of tumor-specific treatments. Traditional chemotherapy relies on the premise that rapidly proliferating cancer cells are more likely to be killed by a cytotoxic agent. In reality, however, cytotoxic agents have very little or no specificity, which leads to systemic toxicity, causing undesirable severe side effects. Consequently, various “molecularly targeted cancer therapies” have been developed for use in specific cancers, including tumor-targeting drug delivery systems. In general, such a drug delivery system consists of a tumor recognition moiety and a cytotoxic “warhead” connected through a “smart” linker to form a conjugate. When a multi-functionalized nanomaterial is used as the vehicle, a “Trojan Horse” approach can be used for mass delivery of cytotoxic “warheads” to maximize the efficacy. Exploitation of the special properties of fluorine has proven successful in the development of new and effective biochemical tools as well as therapeutic agents. Fluorinated congeners can also serve as excellent probes for the investigation of biochemical mechanisms. 19F-NMR can provide unique and powerful tools for mechanistic investigations in chemical biology. This account presents our recent progress, in perspective, on the molecular approaches to the design and development of novel tumor-targeted drug delivery systems for new generation chemotherapy by exploiting the unique nature of fluorine. PMID:23935213

  15. Spermbots: potential impact for drug delivery and assisted reproductive technologies.

    PubMed

    Magdanz, Veronika; Schmidt, Oliver G

    2014-08-01

    Micromotors and nanomotors are an emerging research field that aims at achieving locomotion on the microscale for a variety of applications such as drug delivery, single cell manipulation, microsensors and lab-on-a-chip devices, just to point out a few. The enthusiastic development of hybrid micromotors harnessing biological power sources for physiologically compatible nano/microdevices has recently brought a lot of attention to the international research community that is looking for a solution for the actuation and locomotion on the microscale. This article describes the potential of sperm-driven micro-bio-robots in the biomedical field such as drug delivery or single cell manipulation. Herein, a specific potential of the sperm-driven micro-bio-robot is described that might have impact on the development of assisted reproductive technologies.

  16. Delivery of antifibroblast agents as adjuncts to filtration surgery. Part I--Periocular clearance of cobalt-57 bleomycin in experimental drug delivery: pilot study in the rabbit

    SciTech Connect

    Kay, J.S.; Litin, B.S.; Woolfenden, J.M.; Chvapil, M.; Herschler, J.

    1986-10-01

    Antitumor and antifibroblast agents show promise as adjuncts after glaucoma filtration surgery in reducing postoperative scarring and failure. We used nuclear imaging in rabbits to investigate periocular clearance of one such agent (/sup 57/Co-bleomycin). Sub-Tenon injection was compared to other delivery techniques. Our results showed that a collagen sponge and a silastic disc implant with a microhole prolonged drug delivery when compared to sub-Tenon injection alone or injection with a viscosity enhancing agent (0.5% sodium hyaluronate). We theorize that if an antifibroblast agent can be delivered in small and sustained amounts after filtration surgery, this may prolong bleb longevity and avoid unnecessary drug toxicity.

  17. Preparation, characterization, and potential application of chitosan, chitosan derivatives, and chitosan metal nanoparticles in pharmaceutical drug delivery

    PubMed Central

    Ahmed, Tarek A; Aljaeid, Bader M

    2016-01-01

    Naturally occurring polymers, particularly of the polysaccharide type, have been used pharmaceutically for the delivery of a wide variety of therapeutic agents. Chitosan, the second abundant naturally occurring polysaccharide next to cellulose, is a biocompatible and biodegradable mucoadhesive polymer that has been extensively used in the preparation of micro-as well as nanoparticles. The prepared particles have been exploited as a potential carrier for different therapeutic agents such as peptides, proteins, vaccines, DNA, and drugs for parenteral and nonparenteral administration. Therapeutic agent-loaded chitosan micro- or nanoparticles were found to be more stable, permeable, and bioactive. In this review, we are highlighting the different methods of preparation and characterization of chitosan micro- and nanoparticles, while reviewing the pharmaceutical applications of these particles in drug delivery. Moreover, the roles of chitosan derivatives and chitosan metal nanoparticles in drug delivery have been illustrated. PMID:26869768

  18. Ultrasound guided site specific gene delivery system using adenoviral vectors and commercial ultrasound contrast agents.

    PubMed

    Howard, Candace M; Forsberg, Flemming; Minimo, Corrado; Liu, Ji-Bin; Merton, Daniel A; Claudio, Pier Paolo

    2006-11-01

    We have evaluated if ultrasound imaging (US) and various commercially available contrast microbubbles can serve as a non-invasive systemically administered delivery vehicle for site-specific adenoviral-mediated gene transfer in vitro and in vivo. The contrast agents were tested for their ability to enclose and to protect an adenoviral vector carrying the GFP marker gene (Ad-GFP) into the microbubbles. We have also evaluated the ability of the innate immune system to inactivate free adenoviruses as well as unenclosed viruses adsorbed on the surface of the contrast agents and in turn the ability of the microbubbles to enclose and to protect the viral vectors from such agents. In vitro as well as in vivo, innate components of the immune system were able to serve as inactivating agents to clear free viral particles and unenclosed adenoviruses adsorbed on the microbubbles' surface. Systemic delivery of Ad-GFP enclosed into microbubbles in the tail vein of nude mice resulted in specific targeting of the GFP transgene. Both fluorescence microscopy and GFP immunohistochemistry demonstrated US guided specific transduction in the targeted cells only, with no uptake in either heart, lungs or liver using complement-pretreated Ad-GFP microbubbles. This approach enhances target specificity of US microbubble destruction as a delivery vehicle for viral-mediated gene transfer.

  19. [Bioterrorism, parasites as potential bioterrorism agents and biosecurity studies].

    PubMed

    Aksoy, Umit

    2006-01-01

    A variety of agents have a potential risk for being use as weapons of biological terrorism. However, the use of parasites as bioterrorism agents has not received so much attention. Parasites could contribute to the installation of fear in human population upon intentional addition to their food and water supplies. On the other hand, vector-borne parasites can also constitute risk of bioterrorism. Biosecurity issues are gaining importance as a consequence of globalization. Surveillance is critical in maintaining biosecurity and early detection of infectious disease agents is essential. In this review article, bioterrorism, the role of parasites as potential bioterrorism agents, studies on biosecurity and laboratory design for biosafety have been discussed under the light of recent literature.

  20. Gadolinium oxide nanoparticles as potential multimodal imaging and therapeutic agents.

    PubMed

    Kim, Tae Jeong; Chae, Kwon Seok; Chang, Yongmin; Lee, Gang Ho

    2013-01-01

    Potentials of hydrophilic and biocompatible ligand coated gadolinium oxide nanoparticles as multimodal imaging agents, drug carriers, and therapeutic agents are reviewed. First of all, they can be used as advanced T1 magnetic resonance imaging (MRI) contrast agents because they have r1 larger than those of Gd(III)-chelates due to a high density of Gd(III) per nanoparticle. They can be further functionalized by conjugating other imaging agents such as fluorescent imaging (FI), X-ray computed tomography (CT), positron emission tomography (PET), and single photon emission tomography (SPECT) agents. They can be also useful for drug carriers through morphology modifications. They themselves are also potential CT and ultrasound imaging (USI) contrast and thermal neutron capture therapeutic (NCT) agents, which are superior to commercial iodine compounds, air-filled albumin microspheres, and boron ((10)B) compounds, respectively. They, when conjugated with targeting agents such as antibodies and peptides, will provide enhanced images and be also very useful for diagnosis and therapy of diseases (so called theragnosis).

  1. Injectable Multidomain Peptide Nanofiber Hydrogel as a Delivery Agent for Stem Cell Secretome

    PubMed Central

    Bakota, Erica L.; Wang, Yin; Danesh, Farhad; Hartgerink, Jeffrey D.

    2011-01-01

    Peptide hydrogels show immense promise as therapeutic materials. Here we present a rationally designed multidomain peptide that self-assembles into nanofibers approximately 8 nm wide, 2 nanometers high and microns in length in the presence of Mg2+. At a concentration of 1% by weight, the peptide forms an extensive nanofibers network that results in a physically cross-linked viscoelastic hydrogel. This hydrogel undergoes shear thinning and then quickly recovers nearly 100% of its elastic modulus when the shearing force is released, making it ideal for use as an injectable material. When placed in the presence of human embryonic stem cells (ESCs), the nanofibrous hydrogel acts like a sponge, soaking up the vast array of growth factors and cytokines released by the ESCs. The peptide hydrogel sponge can then be removed from the presence of the ESCs and placed in a therapeutic environment, where it can subsequently release these components. In vitro experiments demonstrate that release of stem cell secretome from these hydrogels in the presence of Glomerular Epithelial Cells treated with high glucose significantly decreased protein permeability in a model of diabetes-induced kidney injury. Tracking experiments were then performed to determine the fate of the hydrogel upon injection in vivo. Hydrogels labeled with a Gd3+ MRI contrast agent were injected into the abdominal cavity of mice and found to remain localized over twenty-four hours. This implies that the hydrogel possesses sufficient rigidity to remain localized and release stem cell secretome over time rather than immediately dissolving in the abdominal cavity. Together, the shear thinning and recovery as observed by rheometry, as well as secretome absorption and release in vivo, demonstrate the potential of the nanofibrous multidomain peptide hydrogel as an injectable delivery agent. PMID:21417437

  2. Novel 2-Aminobenzamides as Potential Orally Active Antithrombotic Agents

    PubMed Central

    2012-01-01

    In an effort to develop potent antithrombotic agents, a series of novel 2-aminobenzamide derivatives were synthesized and screened for their in vivo antithrombotic activity. Among the 23 compounds tested, compound (8g) showed the most promising antithrombotic activity, which was comparable with clinically used aspirin or warfarin, but at variance with these standard drugs, 8g did not exhibit the increased bleeding time, suggesting its potential as a novel antithrombotic agent. PMID:24900559

  3. Dermal and transdermal delivery of an anti-psoriatic agent via ethanolic liposomes.

    PubMed

    Dubey, Vaibhav; Mishra, Dinesh; Dutta, Tathagata; Nahar, Manoj; Saraf, D K; Jain, N K

    2007-11-06

    The aim of the current investigation is to evaluate the transdermal potential of novel vesicular carrier, ethosomes, bearing methotrexate (MTX), an anti-psoriatic, anti-neoplastic, highly hydrosoluble agent having limited transdermal permeation. MTX loaded ethosomes were prepared, optimized and characterized for vesicular shape and surface morphology, vesicular size, entrapment efficiency, stability, in vitro human skin permeation and vesicle-skin interaction. The formulation (EE(9)) having 3% phospholipid content and 45% ethanol showing the greatest entrapment (68.71+/-1.4%) and optimal nanometric size range (143+/-16 nm) was selected for further transdermal permeation studies. Stability profile of prepared system assessed for 120 days revealed very low aggregation and growth in vesicular size (8.8+/-1.2%). MTX loaded ethosomal carriers also provided an enhanced transdermal flux of 57.2+/-4.34 microg/cm(2)/h and decreased lag time of 0.9 h across human cadaver skin. Skin permeation profile of the developed formulation further assessed by confocal laser scanning microscopy (CLSM) revealed an enhanced permeation of Rhodamine Red (RR) loaded formulations to the deeper layers of the skin (170 microm). Also, the formulation retained its penetration power after storage. Vesicle skin interaction study also highlighted the penetration enhancing effect of ethosomes with some visual penetration pathways and corneocytes swelling, a measure of retentive nature of formulation. Our results suggests that ethosomes are an efficient carrier for dermal and transdermal delivery of MTX.

  4. Polymeric nanoparticles as an oral delivery system for biocontrol agents for the brushtail possum (Trichosurus vulpecula).

    PubMed

    McDowell, A; McLeod, B J; Rades, T; Tucker, I G

    2009-12-01

    To investigate polymeric nanoparticles as an oral delivery system for protein biocontrol agents for control of the brushtail possum, Trichosurus vulpecula. Insulin-loaded poly(ethyl 2-cyanoacrylate) (PECA) nanoparticles were prepared using interfacial polymerisation, and characterised for size, zeta potential, and efficiency of encapsulation of insulin. In-vitro release of insulin-loaded PECA nanoparticles was quantified using reverse-phase high-pressure liquid chromatography (HPLC). The in-vivo pharmacokinetics of insulin in PECA nanoparticles was investigated following I/V administration, and when injected directly into the caecum alone or in conjunction with the permeation enhancer EDTA. Blood samples were collected at intervals from -5 to 180 minutes, and the concentration of insulin in plasma was quantified using a radioimmunoassay (RIA) validated for possum plasma. Poly(ethyl 2-cyanoacrylate) nanoparticles were produced with a uniform particle size of 200-300 nm, and the mean entrapment of insulin was 78%. In-vitro release of insulin from the PECA nanoparticles was controlled, although incomplete, and approximately 30% of the insulin remained entrapped. The bioavailability of insulin when administered in a PECA nanoparticulate formulation injected directly into the caecum was <1%, and was not increased by addition of the permeation enhancer. The nanoparticulate formulations investigated as part of this study resulted in low bioavailability of the peptide insulin in the brushtail possum.

  5. Novel methods of local anesthetic delivery in the perioperative and postoperative setting-potential for fibrin hydrogel delivery.

    PubMed

    Kearney, Laura; Whelan, Derek; O'Donnell, Brian D; Clover, Anthony J P

    2016-12-01

    The benefits of high-quality postoperative analgesia are well documented and include earlier mobilization, fewer respiratory and cardiovascular complications, and shorter hospital stay. Local anesthesia-based acute pain regimens are at worst equal to and at best superior to opiate-based regimens from the perspective of analgesia. A multimodal approach limiting opioids by combining with local anesthetics has additional beneficial effect on outcomes such as nausea and vomiting, pruritus, gastrointestinal function, respiratory complications, and neutrophil function. Wound catheters providing continuous infiltration of local anesthetics offer a rational approach to effective perioperative analgesia, but their use is limited by a short duration of action. There is an identified need for further methods to optimize longer-acting delivery of these agents. This article reviews current and evolving longer-acting techniques and their limitations with particular focus on the potential advantages of a fibrin hydrogel-based system. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Boron containing macromolecules and nanovehicles as delivery agents for neutron capture therapy.

    PubMed

    Wu, Gong; Barth, Rolf F; Yang, Weilian; Lee, Robert J; Tjarks, Werner; Backer, Marina V; Backer, Joseph M

    2006-03-01

    Boron neutron capture therapy (BNCT) is based on the nuclear capture and fission reactions that occur when non-radioactive boron-10 is irradiated with low energy thermal neutrons to yield high linear energy transfer (LET) alpha particles ((4)He) and recoiling lithium -7((7)Li) nuclei. For BNCT to be successful, a sufficient number of (10)B atoms ( approximately 10(9) atoms/cell) must be selectively delivered to the tumor and enough thermal neutrons must be absorbed by them to sustain a lethal (10)B(n, alpha) (7)Li capture reaction. BNCT primarily has been used to treat patients with brain tumors, and more recently those with head and neck cancer. Two low molecular weight (LMW) boron delivery agents currently are being used clinically, sodium borocaptate and boronophenylalanine. However, a variety of high molecular weight (HMW) agents consisting of macromolecules and nanovehicles have been developed. This review will focus on the latter which include: monoclonal antibodies, dendrimers, liposomes, dextrans, polylysine, avidin, folic acid, and epidermal and vascular endothelial growth factors (EGF and VEGF). Procedures for introducing boron atoms into these HMW agents and their chemical properties will be discussed. In vivo studies on their biodistribution will be described, and the efficacy of a subset of them, which have been used for BNCT of tumors in experimental animals, will be discussed. Since brain tumors currently are the primary candidates for treatment by BNCT, delivery of these HMW agents across the blood-brain barrier presents a special challenge. Various routes of administration will be discussed including receptor-facilitated transcytosis following intravenous administration, direct intratumoral injection and convection enhanced delivery by which a pump is used to apply a pressure gradient to establish bulk flow of the HMW agent during interstitial infusion. Finally, we will conclude with a discussion relating to issues that must be addressed if these

  7. Intradermal administration of fluorescent contrast agents for delivery to axillary lymph nodes

    NASA Astrophysics Data System (ADS)

    Rasmussen, John C.; Meric-Berstam, Funda; Krishnamurthy, Savitri; Tan, I.-Chih; Zhu, Banghe; Wagner, Jamie L.; Babiera, Gildy V.; Mittendorf, Elizabeth A.; Sevick-Muraca, Eva M.

    2014-05-01

    In this proof-of-concept study we seek to demonstrate the delivery of fluorescent contrast agent to the tumor-draining lymph node basin following intraparenchymal breast injections and intradermal arm injection of micrograms of indocyanine green in 20 breast cancer patients undergoing complete axillary lymph node dissection. Individual lymph nodes were assessed ex vivo for presence of fluorescent signal. In all, 88% of tumor-negative lymph nodes and 81% of tumor-positive lymph nodes were fluorescent. These results indicate that future studies utilizing targeted fluorescent contrast agents may demonstrate improved surgical and therapeutic intervention.

  8. Nanocomposite scaffolds with tunable mechanical and degradation capabilities: co-delivery of bioactive agents for bone tissue engineering.

    PubMed

    Cattalini, Juan P; Roether, Judith; Hoppe, Alexander; Pishbin, Fatemeh; Haro Durand, Luis; Gorustovich, Alejandro; Boccaccini, Aldo R; Lucangioli, Silvia; Mouriño, Viviana

    2016-10-21

    Novel multifunctional nanocomposite scaffolds made of nanobioactive glass and alginate crosslinked with therapeutic ions such as calcium and copper were developed for delivering therapeutic agents, in a highly controlled and sustainable manner, for bone tissue engineering. Alendronate, a well-known antiresorptive agent, was formulated into microspheres under optimized conditions and effectively loaded within the novel multifunctional scaffolds with a high encapsulation percentage. The size of the cation used for the alginate crosslinking impacted directly on porosity and viscoelastic properties, and thus, on the degradation rate and the release profile of copper, calcium and alendronate. According to this, even though highly porous structures were created with suitable pore sizes for cell ingrowth and vascularization in both cases, copper-crosslinked scaffolds showed higher values of porosity, elastic modulus, degradation rate and the amount of copper and alendronate released, when compared with calcium-crosslinked scaffolds. In addition, in all cases, the scaffolds showed bioactivity and mechanical properties close to the endogenous trabecular bone tissue in terms of viscoelasticity. Furthermore, the scaffolds showed osteogenic and angiogenic properties on bone and endothelial cells, respectively, and the extracts of the biomaterials used promoted the formation of blood vessels in an ex vivo model. These new bioactive nanocomposite scaffolds represent an exciting new class of therapeutic cell delivery carrier with tunable mechanical and degradation properties; potentially useful in the controlled and sustainable delivery of therapeutic agents with active roles in bone formation and angiogenesis, as well as in the support of cell proliferation and osteogenesis for bone tissue engineering.

  9. Advances in drug delivery system for platinum agents based combination therapy

    PubMed Central

    Kang, Xiang; Xiao, Hai-Hua; Song, Hai-Qin; Jing, Xia-Bin; Yan, Le-San; Qi, Ruo-Gu

    2015-01-01

    Platinum-based anticancer agents are widely used as first-line drugs in cancer chemotherapy for various solid tumors. However, great side effects and occurrence of resistance remain as the major drawbacks for almost all the platinum drugs developed. To conquer these problems, new strategies should be adopted for platinum drug based chemotherapy. Modern nanotechnology has been widely employed in the delivery of various therapeutics and diagnostic. It provides the possibility of targeted delivery of a certain anticancer drug to the tumor site, which could minimize toxicity and optimize the drug efficacy. Here, in this review, we focused on the recent progress in polymer based drug delivery systems for platinum-based combination therapy. PMID:26779373

  10. Advances in drug delivery system for platinum agents based combination therapy.

    PubMed

    Kang, Xiang; Xiao, Hai-Hua; Song, Hai-Qin; Jing, Xia-Bin; Yan, Le-San; Qi, Ruo-Gu

    2015-12-01

    Platinum-based anticancer agents are widely used as first-line drugs in cancer chemotherapy for various solid tumors. However, great side effects and occurrence of resistance remain as the major drawbacks for almost all the platinum drugs developed. To conquer these problems, new strategies should be adopted for platinum drug based chemotherapy. Modern nanotechnology has been widely employed in the delivery of various therapeutics and diagnostic. It provides the possibility of targeted delivery of a certain anticancer drug to the tumor site, which could minimize toxicity and optimize the drug efficacy. Here, in this review, we focused on the recent progress in polymer based drug delivery systems for platinum-based combination therapy.

  11. Potential and problems in ultrasound-responsive drug delivery systems

    PubMed Central

    Zhao, Ying-Zheng; Du, Li-Na; Lu, Cui-Tao; Jin, Yi-Guang; Ge, Shu-Ping

    2013-01-01

    Ultrasound is an important local stimulus for triggering drug release at the target tissue. Ultrasound-responsive drug delivery systems (URDDS) have become an important research focus in targeted therapy. URDDS include many different formulations, such as microbubbles, nanobubbles, nanodroplets, liposomes, emulsions, and micelles. Drugs that can be loaded into URDDS include small molecules, biomacromolecules, and inorganic substances. Fields of clinical application include anticancer therapy, treatment of ischemic myocardium, induction of an immune response, cartilage tissue engineering, transdermal drug delivery, treatment of Huntington’s disease, thrombolysis, and disruption of the blood–brain barrier. This review focuses on recent advances in URDDS, and discusses their formulations, clinical application, and problems, as well as a perspective on their potential use in the future. PMID:23637531

  12. New functional handle for use as a self-reporting contrast and delivery agent in nanomedicine.

    PubMed

    Robin, Mathew P; Mabire, Anne B; Damborsky, Joanne C; Thom, Elizabeth S; Winzer-Serhan, Ursula H; Raymond, Jeffery E; O'Reilly, Rachel K

    2013-06-26

    The synthesis and photophysical characterization of a chromophore-bridged block copolymer system is presented. This system is based on a dithiomaleimide (DTM) functional group as a highly emissive functionality which can readily be incorporated into polymeric scaffolds. A key advantage of this new reporter group is its versatile chemistry, ease of further functionalization, and notably small size, which allows for ready incorporation without affecting or disrupting the self-assembly process critical to the formation of core-shell polymeric contrast and drug delivery agents. We demonstrate the potential of this functionality with a diblock system which has been shown to be appropriate for micellization and, when in the micellar state, does not self-quench. The block copolymer is shown to be significantly more emissive than the lone dye, with a concentration-independent emission and anisotropy profile from 1.5 mM to 0.15 μM. An emission lifetime and anisotropy decay comparison of the block copolymer to its micelle displays that time-domain fluorescence lifetime imaging (FLIM) is able to rapidly resolve differences in the supramolecular state of this block-dye-block polymer system. Furthermore, the ability to resolve these differences in the supramolecular state means that the DTM micelles are capable of self-reporting when disassembly occurs, simply by monitoring with FLIM. We demonstrate the great potential for in vitro applications that this system provides by using FLIM to observe micelle disassembly in different vascular components of rat hippocampal tissue. In total this system represents a new class of in-chain emitter which is appropriate for application in quantitative imaging and the tracking of particle degradation/disassembly events in biological environments.

  13. Ethosomes: versatile vesicular carriers for efficient transdermal delivery of therapeutic agents.

    PubMed

    Pandey, Vikas; Golhani, Dilip; Shukla, Rajesh

    2015-12-01

    Delivery across skin is attractive due to its easy accessibility. However, drug delivery across skin is still a challenge in biomedical sciences. Over the past few decades, various successful novel devices and techniques have emerged to optimize drug delivery across skin whose obstructing behavior constricts entry of most of the therapeutic agents. Inability of various conventional vesicular formulations, e.g. liposomes to pass through the tapered (>30 nm) intercellular channels of stratum corneum, rendered invention of some lipid based vesicular carrier systems such as ethosomes which consist of phospholipid, ethanol and water. Ethosomes are non-invasive delivery carriers that enable drugs to reach the deep skin layers and/or the systemic circulation. In spite of their sophistication in conceptuality, they are exemplified by easiness in their preparation, safety and efficacy - a combination that can highly inflate their application. This review attempts to describe all aspects of ethosomes including roles and upshots of different excipients, various methods of preparation and characterizations, research reports on various drug deliveries, patent reports and future prospects.

  14. Casein/pectin nanocomplexes as potential oral delivery vehicles.

    PubMed

    Luo, Yangchao; Pan, Kang; Zhong, Qixin

    2015-01-01

    Delivery systems prepared with natural biopolymers are of particular interests for applications in food, pharmaceutics and biomedicine. In this study, nanocomplex particles of sodium caseinate (NaCas) and pectin were fabricated and investigated as potential oral delivery vehicles. Nanocomplexes were prepared with three mass ratios of NaCas/pectin by acidification using glucono-δ-lactone and thermal treatment. NaCas/pectin at 1:1 mass ratio resulted in dispersions with the lowest turbidity and the smallest and most uniform nanocomplexes. Thermal treatment at 85 °C for 30 min facilitated the formation of stable, compact, and spherical nanocomplexes. Heating not only greatly increased the yield of nanocomplexes but also significantly improved the encapsulation capability of rutin studied as a model compound. Pectin in nanocomplexes delayed the hydrolysis of NaCas by pepsin at gastric conditions and enabled the controlled release of most rutin in simulated intestinal conditions. The nanocomplexes based on food-sourced biopolymers have promising features for oral delivery of nutrients and medicines. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. A polymer-based drug delivery system for the antineoplastic agent bis(maltolato)oxovanadium in mice.

    PubMed Central

    Jackson, J. K.; Min, W.; Cruz, T. F.; Cindric, S.; Arsenault, L.; Von Hoff, D. D.; Degan, D.; Hunter, W. L.; Burt, H. M.

    1997-01-01

    Using vanadyl sulphate, sodium orthovanadate or bis(maltolato)oxovanadium (BMOV), Cruz TF, Morgan A, Min W (1995, Mol Cell Biochem 153: 161-166) have recently demonstrated the antineoplastic effects of vanadium in mice. In this study, the antineoplastic effects of BMOV against human tumour cell lines was confirmed, and this effect was shown to depend on the prolonged exposure of the cells to the drug. We have investigated a polymeric drug delivery system for the sustained delivery of BMOV as an antineoplastic agent in mice. The objective was to design and evaluate an injectable polymer-BMOV paste that would act as a drug implant for the slow but sustained release of BMOV in the mice. In vitro studies showed that the biodegradable polymer poly (Ghlr epsilon epsilon-caprolactone) (PCL) released BMOV in a sustained manner with rates of drug release increasing with increased loading of the drug in the polymer. In vivo studies showed that PCL-BMOV paste implants produced a concentration-dependent inhibition of MDAY-D2 tumour growth via systemic drug delivery. Further in vivo studies showed that 5% BMOV-loaded PCL (containing 20% methoxypolyethylene glycol) was effective in preventing tumour regrowth of resected RIF tumour masses in mice when the PCL-BMOV paste was applied to the resected site for localized drug delivery. The results confirm the potential of vanadium as an antineoplastic agent and show that the injectable PCL-BMOV formulation releases a chemotherapeutic dose of vanadium for the systemic treatment of whole tumours as well as the localized treatment of resected RIF tumours. Images Figure 3 PMID:9083337

  16. Zeta potential changing phosphorylated nanocomplexes for pDNA delivery.

    PubMed

    Bonengel, Sonja; Prüfert, Felix; Jelkmann, Max; Bernkop-Schnürch, Andreas

    2016-05-17

    The objective of this study was to evaluate the suitability of a zeta potential changing system as gene delivery system. The phosphate ester bearing ligand 6-phosphogluconic acid (6-PGA) was attached to linear and branched polyethyleneimine (PEI) via a carbodiimide-mediated reaction whereby 287 μmol and 413 μmol 6-PGA could be coupled per gram polymer. Nanocomplexes of these modified polymers with pDNA showed a zeta potential of +12 mV for nanocomplexes with the linear PEI-6PGA and +16 mV in case of the branched derivative. By the addition of carboxymethylcellulose (CMC), zeta potentials of the complexes were reduced to +2.86 and +3.25, respectively. Phosphate release studies on Caco 2 cells and HEK-293 cells demonstrated the ability to cleave the phosphate ester. Compared to HEK-293 cells, enzymatic degradation of the phosphate ester in Caco 2 cells was 2.3-fold higher from nanocomplexes comprising linear PEI and 4.3-fold higher from those with branched PEI. Furthermore, incubation with alkaline phosphatase led to an increase in the zeta potential of nanocomplexes based on linear PEI-6PGA to +6.96mV and +8.26 mV in nanocomplexes comprising branched PEI-6PGA. Studying transfection efficiency in Caco 2 cells and HEK-293 cells, a higher expression of the green fluorescent protein (GFP) could be detected in HEK-293 cells. In presence of a phosphate inhibitor, transfection efficiencies were decreased in both cells lines, due to a lacking shift of the zeta potential of the tested pDNA complexes. According to these results, zeta potential changing systems seem to be a promising strategy for future gene delivery systems, as this concept allows the in situ generation of positive charges in close proximity to the cellular surface.

  17. Progress in Nanotechnology Based Approaches to Enhance the Potential of Chemopreventive Agents

    PubMed Central

    Muqbil, Irfana; Masood, Ashiq; Sarkar, Fazlul H.; Mohammad, Ramzi M.; Azmi, Asfar S.

    2011-01-01

    Cancer chemoprevention is defined as the use of natural agents to suppress, reverse or prevent the carcinogenic process from turning into aggressive cancer. Over the last two decades, multiple natural dietary compounds with diverse chemical structures such flavonoids, tannins, curcumins and polyphenols have been proposed as chemopreventive agents. These agents have proven excellent anticancer potential in the laboratory setting, however, the observed effects in vitro do not translate in clinic where they fail to live up to their expectations. Among the various reasons for this discrepancy include inefficient systemic delivery and robust bioavailability. To overcome this barrier, researchers have focused towards coupling these agents with nano based encapsulation technology that in principle will enhance bioavailability and ultimately benefit clinical outcome. The last decade has witnessed rapid advancement in the development of nanochemopreventive technology with emergence of many nano encapsulated formulations of different dietary anticancer agents. This review summarizes the most up-to-date knowledge on the studies performed in nanochemoprevention, their proposed use in the clinic and future directions in which this field is heading. As the knowledge of the dynamics of nano encapsulation evolves, it is expected that researchers will bring forward newer and far more superior nanochemopreventive agents that may become standard drugs for different cancers. PMID:24212623

  18. Primary screen for potential sheep scab control agents.

    PubMed

    Dunn, J A; Prickett, J C; Collins, D A; Weaver, R J

    2016-07-15

    The efficacy of potential acaricidal agents were assessed against the sheep scab mite Psoroptes ovis using a series of in vitro assays in modified test arenas designed initially to maintain P. ovis off-host. The mortality effects of 45 control agents, including essential oils, detergents, desiccants, growth regulators, lipid synthesis inhibitors, nerve action/energy metabolism disruptors and ecdysteroids were assessed against adults and nymphs. The most effective candidates were the desiccants (diatomaceous earth, nanoclay and sorex), the growth regulators (buprofezin, hexythiazox and teflubenzuron), the lipid synthesis inhibitors (spirodiclofen, spirotetramat and spiromesifen) and the nerve action and energy metabolism inhibitors (fenpyroximate, spinosad, tolfenpyrad, and chlorantraniliprole).

  19. Potential applications for halloysite nanotubes based drug delivery systems

    NASA Astrophysics Data System (ADS)

    Sun, Lin

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

  20. Enhanced transdermal delivery of an anti-HIV agent via ethanolic liposomes.

    PubMed

    Dubey, Vaibhav; Mishra, Dinesh; Nahar, Manoj; Jain, Vikas; Jain, Narendra Kumar

    2010-08-01

    Indinavir, as a protease inhibitor with a short biological half life, variable pH-dependent oral absorption, and extensive first-pass metabolism, presents a challenge with respect to its oral administration. The current work aims to formulate and characterize indinavir-bearing ethanolic liposomes (ethosomes), and to investigate their enhanced transdermal delivery potential. The prepared ethanolic liposomes were characterized to be spherical, unilamellar structures having low polydispersity, nanometric size range, and improved entrapment efficiency over other delivery formulations. Permeation studies of indinavir across human cadaver skin resulted in enhanced transdermal flux from ethanolic liposomes that was significantly (P < 0.05) greater than that with ethanolic drug solution, conventional liposomes, or plain drug solution. Additionally, the ethanolic liposomes showed the shortest lag time for indinavir, thus presenting a suitable approach for transdermal delivery of this protease inhibitor. From the clinical editor: This study characterizes indinavir bearing ethanolic liposomes (ethosomes), and investigate their enhanced transdermal delivery potential, demonstrating a potentially a suitable approach for transdermal delivery of this protease inhibitor for HIV treatment, which typically has been associated with limited bioavailability via the oral route.

  1. Delivery of imaging and therapeutic agents to tumor using pHLIP

    NASA Astrophysics Data System (ADS)

    Wijesinghe, Dayanjali; Moshnikova, Anna; Rossi, Bethany; Engelman, Donald; Andreev, Oleg; Reshetnyak, Yana

    2012-02-01

    We are developing a novel technology for selective delivery of imaging probes and membrane-impermeable molecules to cancer cells. It is based on action of water-soluble membrane peptide, pHLIP^ (pH [Low] Insertion Peptide), which has ability to insert and fold in cellular membrane at slightly acidic environment, which is a characteristic for various pathological states including cancer. The insertion of the peptide is unidirectional: C-terminus moves inside the cell across membrane, while N-terminus flags outside. Thus pHLIP possess dual delivery capability. Imaging agents (fluorescent, PET, SPECT or MRI) could be attached to the N-terminus of the peptide to mark tumor mass and tumor margins with high precision. At the same time, therapeutic molecules attached to the C-inserting end, could be moved across membrane to reach cytoplasmic target. Among translocated molecules are synthetic cyclic peptides, gene regulation agent (peptide nucleic acid) and phalla- and amanita toxins with hydrophobicity tuned by attachment of fatty acids for optimum delivery. Currently we have family of pHLIP peptides for various applications. The work is supported by NIH grants CA133890 to OAA, DME, YRK.

  2. Cationic nanoemulsions as potential carriers for intracellular delivery

    PubMed Central

    Khachane, P.V.; Jain, A.S.; Dhawan, V.V.; Joshi, G.V.; Date, A.A.; Mulherkar, R.; Nagarsenker, M.S.

    2014-01-01

    Successful cytosolic delivery enables opportunities for improved treatment of various genetic disorders, infectious diseases and cancer. Cationic nanoemulsions were designed using alternative excipients and evaluated for particle size, charge, effect of sterilization on its stability, DNA condensation potential and cellular uptake efficiency. Various concentrations of non-ionic and ionic stabilizers were evaluated to design formula for colloidally stable cationic nanoemulsion. The nanoemulsion comprised of 5% Capmul MCM, 0.5% didodecyldimethylammonium bromide (DDAB), 1% phospholipid, 1% Poloxamer 188 and 2.25% glycerol and possessed particle size of 81.6 ± 3.56 nm and 137.1 ± 1.57 nm before and after steam sterilization, respectively. DNA condensation studies were carried out at various nanoemulsion: DNA ratios ranging from 1:1 to 10:1. Cell uptake studies were conducted on human embryonic kidney (HEK) cell lines which are widely reported for transfection studies. The nanoemulsions showed excellent cellular uptake as evaluated by fluorescence microscopy and flow cytometry. Overall, a colloidally stable cationic nanoemulsion with good DNA condensation ability was successfully fabricated for efficient cytosolic delivery and potential for in vivo effectiveness. PMID:25972740

  3. Mustard: a potential agent of chemical warfare and terrorism.

    PubMed

    Saladi, R N; Smith, E; Persaud, A N

    2006-01-01

    As one of the most important vesicant agents, the destructive properties of mustards on the skin, eyes and respiratory system, combined with a lack of antidote, makes them effective weapons. Such weapons are inexpensive, easily obtainable and frequently stockpiled. Sulphur mustard (mustard gas) has been used as a chemical warfare agent in at least 10 conflicts. In this article, the use of mustard as a potential agent of chemical warfare and terrorism is outlined. The dose-dependent effects of acute sulphur mustard exposure on the skin, eyes, and respiratory system are described, as well as the possible extents of injuries, the mechanisms of action and the long-term complications. Prevention and management of mustard exposure are briefly discussed. The need for awareness and preparedness in the dermatological community regarding mustard exposure is emphasized.

  4. Reacetylated chitosan microspheres for controlled delivery of anti-microbial agents to the gastric mucosa.

    PubMed

    Portero, A; Remuñán-López, C; Criado, M T; Alonso, M J

    2002-01-01

    The high aqueous solubility of chitosan restricts the utility of chitosan microspheres for gastric drug delivery. This paper describes the preparation of reacetylated chitosan microspheres with suitable properties for the controlled release of active anti-microbial agents, such as amoxycillin and metronidazole, in the gastric cavity. Two different microencapsulation approaches were developed and optimized in order to encapsulate hydrophilic (amoxycillin) and hydrophobic (metronidazole) compounds efficiently. The reacetylated chitosan microspheres exhibited a controlled water swelling capacity and gelified at acidic pH, resulting in prolonged release of the encapsulated antibiotics. The reacetylation time was found to be a key factor that affects not only drug release, but also encapsulation efficiency and anti-microbial activity of the encapsulated compound. The last two parameters were also dependent on drug solubility in the reacetylating agent. Using short reacetylation time periods, it was possible to efficiently control the release of both hydrophilic and lipophilic antibiotics while maintaining their activity against different bacteria. Consequently, reacetylated chitosan microspheres are promising vehicles for the controlled delivery of anti-microbial agents to the gastric cavity and, hence, for the eradication of Helicobacter pylori, a pathogen strongly associated with gastric ulcers and possibly gastric carcinoma.

  5. Insonation frequency selection may assist detection and therapeutic delivery of targeted ultrasound contrast agents.

    PubMed

    Payne, Edward; Ooi, Andrew; Manasseh, Richard

    2011-02-01

    Ultrasound-targeted drug delivery relies on the unique nature of ultrasound contrast agents--they are microbubbles that respond strongly to ultrasound. Intravenously injected microbubbles are smaller than a blood cell. By increasing the ultrasound power, the bubbles can be ruptured at the targeted endothelial wall, locally releasing any molecules in the bubble shell. Furthermore, ultrasound-activated microbubbles are known to cause sonoporation--the process by which ultrasound drives molecules through cellular membranes. However, techniques are required to selectively detect and rupture only those microbubbles on target walls. Experiments are presented on the behaviour of microbubbles on walls. For accuracy, imaging measurements are made on model microbubbles larger than contrast agents. Bubble size was varied and the resonant frequency peak determined. Microbubbles on walls have a shifted frequency in good agreement with theory: a 20-25% downshift from the frequency when far from walls. Effects other than the presence of the wall account for less than 5% of the shift. Theory predicts the frequency downshift should be sustained for actual contrast-agent sized bubbles. The effect of real, compliant cell walls requires investigation. An appropriate downshift in the applied ultrasound frequency could selectively tune gene or drug delivery. To make this feasible, it may be necessary to manufacture monodispersed microbubbles.

  6. Methods for determining agent concentration profiles in agarose gel during convection-enhanced delivery.

    PubMed

    Sindhwani, Nikhil; Ivanchenko, Oleksandr; Lueshen, Eric; Prem, Komal; Linninger, Andreas A

    2011-03-01

    Convection-enhanced delivery (CED) is a promising technique to deliver large molecular weight drugs to the human brain for treatment of Parkinson's, Alzheimer's, or brain tumors. Researchers have used agarose gels to study mechanisms of agent transport in soft tissues like brain due to its similar mechanical and transport properties. However, inexpensive quantitative techniques to precisely measure achieved agent distribution in agarose gel phantoms during CED are missing. Such precise measurements of concentration distribution are needed to optimize drug delivery. An optical experimental method to accurately quantify agent concentration in agarose is presented. A novel geometry correction algorithm is used to determine real concentrations from observable light intensities captured by a digital camera. We demonstrate the technique in dye infusion experiments that provide cylindrical and spherical distributions when infusing with porous membrane and conventional single-port catheters, respectively. This optical method incorporates important parameters, such as optimum camera exposure, captured camera intensity calibration, and use of collimated light source for maximum precision. We compare experimental results with numerical solutions to the convection diffusion equation. The solutions of convection-diffusion equations in the cylindrical and spherical domains were found to match the experimental data obtained by geometry correction algorithm.

  7. Ferrous iron-dependent drug delivery enables controlled and selective release of therapeutic agents in vivo.

    PubMed

    Deu, Edgar; Chen, Ingrid T; Lauterwasser, Erica M W; Valderramos, Juan; Li, Hao; Edgington, Laura E; Renslo, Adam R; Bogyo, Matthew

    2013-11-05

    The precise targeting of cytotoxic agents to specific cell types or cellular compartments is of significant interest in medicine, with particular relevance for infectious diseases and cancer. Here, we describe a method to exploit aberrant levels of mobile ferrous iron (Fe(II)) for selective drug delivery in vivo. This approach makes use of a 1,2,4-trioxolane moiety, which serves as an Fe(II)-sensitive "trigger," making drug release contingent on Fe(II)-promoted trioxolane fragmentation. We demonstrate in vivo validation of this approach with the Plasmodium berghei model of murine malaria. Malaria parasites produce high concentrations of mobile ferrous iron as a consequence of their catabolism of host hemoglobin in the infected erythrocyte. Using activity-based probes, we successfully demonstrate the Fe(II)-dependent and parasite-selective delivery of a potent dipeptidyl aminopeptidase inhibitor. We find that delivery of the compound in its Fe(II)-targeted form leads to more sustained target inhibition with greatly reduced off-target inhibition of mammalian cathepsins. This selective drug delivery translates into improved efficacy and tolerability. These findings demonstrate the utility of a purely chemical means to achieve selective drug targeting in vivo. This approach may find useful application in parasitic infections and more broadly in any disease state characterized by aberrant production of reactive ferrous iron.

  8. Harnessing the power of cell-penetrating peptides: activatable carriers for targeting systemic delivery of cancer therapeutics and imaging agents.

    PubMed

    MacEwan, Sarah R; Chilkoti, Ashutosh

    2013-01-01

    Targeted delivery of cancer therapeutics and imaging agents aims to enhance the accumulation of these molecules in a solid tumor while avoiding uptake in healthy tissues. Tumor-specific accumulation has been pursued with passive targeting by the enhanced permeability and retention effect, as well as with active targeting strategies. Active targeting is achieved by functionalization of carriers to allow specific interactions between the carrier and the tumor environment. Functionalization of carriers with ligands that specifically interact with overexpressed receptors on cancer cells represents a classic approach to active tumor targeting. Cell-penetrating peptides (CPPs) provide a non-specific and receptor-independent mechanism to enhance cellular uptake that offers an exciting alternative to traditional active targeting approaches. While the non-specificity of CPP-mediated internalization has the intriguing potential to make this approach applicable to a wide range of tumor types, their promiscuity is, however, a significant barrier to their clinical utility for systemically administered applications. Many approaches have been investigated to selectively turn on the function of systemically delivered CPP-functionalized carriers specifically in tumors to achieve targeted delivery of cancer therapeutics and imaging agents.

  9. Harnessing the power of cell-penetrating peptides: Activatable carriers for targeting systemic delivery of cancer therapeutics and imaging agents

    PubMed Central

    MacEwan, Sarah R.

    2012-01-01

    Targeted delivery of cancer therapeutics and imaging agents aims to enhance the accumulation of these molecules in a solid tumor while avoiding uptake in healthy tissues. Tumor-specific accumulation has been pursued with passive targeting by the enhanced permeability and retention effect, as well as with active targeting strategies. Active targeting is achieved by functionalization of carriers to allow specific interactions between the carrier and the tumor environment. Functionalization of carriers with ligands that specifically interact with overexpressed receptors on cancer cells represents a classic approach to active tumor targeting. Cell-penetrating peptides (CPPs) provide a non-specific and receptor-independent mechanism to enhance cellular uptake that offers an exciting alternative to traditional active targeting approaches. While the non-specificity of CPP-mediated internalization has the intriguing potential to make this approach applicable to a wide range of tumor types, their promiscuity is, however, a significant barrier to their clinical utility for systemically administered applications. Many approaches have been investigated to selectively turn on the function of systemically delivered CPP-functionalized carriers specifically in tumors to achieve targeted delivery of cancer therapeutics and imaging agents. PMID:22977001

  10. Paclitaxel-loaded chitosan oligosaccharide-stabilized gold nanoparticles as novel agents for drug delivery and photoacoustic imaging of cancer cells.

    PubMed

    Manivasagan, Panchanathan; Bharathiraja, Subramaniyan; Bui, Nhat Quang; Lim, In Gweon; Oh, Junghwan

    2016-09-10

    Polymer nanoparticles have gained significant attention as potential drug carriers for anticancer agents and molecular imaging. Biocompatible gold nanoparticles (AuNPs) were synthesized using chitosan oligosaccharide (COS) as a reducing and stabilizing agent and were subsequently loaded with paclitaxel (PTX) to demonstrate their use in drug delivery and photoacoustic imaging (PAI) of MDA-MB-231 cells. Paclitaxel-loaded chitosan oligosaccharide-stabilized gold nanoparticles (PTX-COS AuNPs) were spherical in shape with an average particle size of 61.86±3.01nm. PTX-COS AuNPs showed sustained and pH-dependent drug release profiles and exhibited strong cytotoxic effect against MDA-MB-231 cells through the induction of apoptosis with improved reactive oxygen species (ROS) generation and altered mitochondrial membrane potential (MMP) level. The cellular internalization of PTX-COS AuNPs was proven by fluorescence microscopy as well as flow cytometry. PTX-COS AuNPs were also evaluated as a new class of optical contrast agents for photoacoustic imaging (PAI). To the best of our knowledge, this is the first report that describes the use of PTX-COS AuNPs as novel agents for drug delivery and PAI of cancer cells. These results exposed the promising potential of PTX-COS AuNPs in the field of drug delivery, molecular imaging, and cancer therapy in the near future. Copyright © 2016. Published by Elsevier B.V.

  11. Nipah virus--a potential agent of bioterrorism?

    PubMed

    Lam, Sai-Kit

    2003-01-01

    Nipah virus, a newly emerging deadly paramyxovirus isolated during a large outbreak of viral encephalitis in Malaysia, has many of the physical attributes to serve as a potential agent of bioterrorism. The outbreak caused widespread panic and fear because of its high mortality and the inability to control the disease initially. There were considerable social disruptions and tremendous economic loss to an important pig-rearing industry. This highly virulent virus, believed to be introduced into pig farms by fruit bats, spread easily among pigs and was transmitted to humans who came into close contact with infected animals. From pigs, the virus was also transmitted to other animals such as dogs, cats, and horses. The Nipah virus has the potential to be considered an agent of bioterrorism.

  12. First polymer "ruthenium-cyclopentadienyl" complex as potential anticancer agent.

    PubMed

    Valente, Andreia; Garcia, Maria Helena; Marques, Fernanda; Miao, Yong; Rousseau, Cyril; Zinck, Philippe

    2013-10-01

    d-glucose end-capped polylactide ruthenium cyclopentadienyl complex (RuPMC) was newly synthesized by a straightforward method. RuPMC was tested against human MCF7 and MDAMB231 breast and A2780 ovarian adenocarcinoma revealing IC50 values in the micromolar range. A pH dependent hydrolysis is advanced by preliminary UV-visible spectroscopy. Cellular distribution studies showed that RuPMC is predominantly found in the nucleus and in the membrane. Data suggest potential application of RuPMC as a new drug delivery system for Ru(II)Cp compounds. © 2013.

  13. Bionanocomposites containing magnetic graphite as potential systems for drug delivery.

    PubMed

    Ribeiro, Lígia N M; Alcântara, Ana C S; Darder, Margarita; Aranda, Pilar; Herrmann, Paulo S P; Araújo-Moreira, Fernando M; García-Hernández, Mar; Ruiz-Hitzky, Eduardo

    2014-12-30

    New magnetic bio-hybrid matrices for potential application in drug delivery are developed from the assembly of the biopolymer alginate and magnetic graphite nanoparticles. Ibuprofen (IBU) intercalated in a Mg-Al layered double hydroxide (LDH) was chosen as a model drug delivery system (DDS) to be incorporated as third component of the magnetic bionanocomposite DDS. For comparative purposes DDS based on the incorporation of pure IBU in the magnetic bio-hybrid matrices were also studied. All the resulting magnetic bionanocomposites were processed as beads and films and characterized by different techniques with the aim to elucidate the role of the magnetic graphite on the systems, as well as that of the inorganic brucite-like layers in the drug-loaded LDH. In this way, the influence of both inorganic components on the mechanical properties, the water uptake ability, and the kinetics of the drug release from these magnetic systems were determined. In addition, the possibility of modulating the levels of IBU release by stimulating the bionanocomposites with an external magnetic field was also evaluated in in vitro assays. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Novel drug delivery systems for actinides (uranium and plutonium) decontamination agents.

    PubMed

    Fattal, Elias; Tsapis, Nicolas; Phan, Guillaume

    2015-08-01

    The possibility of accidents in the nuclear industry or of nuclear terrorist attacks makes the development of new decontamination strategies crucial. Among radionuclides, actinides such as uranium and plutonium and their different isotopes are considered as the most dangerous contaminants, plutonium displaying mostly a radiological toxicity whereas uranium exhibits mainly a chemical toxicity. Contamination occurs through ingestion, skin or lung exposure with subsequent absorption and distribution of the radionuclides to different tissues where they induce damaging effects. Different chelating agents have been synthesized but their efficacy is limited by their low tissue specificity and high toxicity. For these reasons, several groups have developed smart delivery systems to increase the local concentration of the chelating agent or to improve its biodistribution. The aim of this review is to highlight these strategies.

  15. Enhanced Delivery of Gold Nanoparticles with Therapeutic Potential for Targeting Human Brain Tumors

    NASA Astrophysics Data System (ADS)

    Etame, Arnold B.

    The blood brain barrier (BBB) remains a major challenge to the advancement and application of systemic anti-cancer therapeutics into the central nervous system. The structural and physiological delivery constraints of the BBB significantly limit the effectiveness of conventional chemotherapy, thereby making systemic administration a non-viable option for the vast majority of chemotherapy agents. Furthermore, the lack of specificity of conventional systemic chemotherapy when applied towards malignant brain tumors remains a major shortcoming. Hence novel therapeutic strategies that focus both on targeted and enhanced delivery across the BBB are warranted. In recent years nanoparticles (NPs) have emerged as attractive vehicles for efficient delivery of targeted anti-cancer therapeutics. In particular, gold nanoparticles (AuNPs) have gained prominence in several targeting applications involving systemic cancers. Their enhanced permeation and retention within permissive tumor microvasculature provide a selective advantage for targeting. Malignant brain tumors also exhibit transport-permissive microvasculature secondary to blood brain barrier disruption. Hence AuNPs may have potential relevance for brain tumor targeting. However, the permeation of AuNPs across the BBB has not been well characterized, and hence is a potential limitation for successful application of AuNP-based therapeutics within the central nervous system (CNS). In this dissertation, we designed and characterized AuNPs and assessed the role of polyethylene glycol (PEG) on the physical and biological properties of AuNPs. We established a size-dependent permeation profile with respect to core size as well as PEG length when AuNPs were assessed through a transport-permissive in-vitro BBB. This study was the first of its kind to systematically examine the influence of design on permeation of AuNPs through transport-permissive BBB. Given the significant delivery limitations through the non

  16. Annona species (Annonaceae): a rich source of potential antitumor agents?

    PubMed

    Tundis, Rosa; Xiao, Jianbo; Loizzo, Monica R

    2017-06-01

    Plants have provided the basis of traditional medicine systems throughout the world for thousands of years and continue to yield molecules for new remedies. We analyzed studies published from 2009 to 2016 on the Annona species (Annonaceae), including A. coriacea, A. crassifolia, A. hypoglauca, A. muricata, A. squamosa, A. sylvatica, and A. vepretorum, as sources of potential antitumor agents. Here, we report and discuss the mechanisms of action and structure-activity relationships of the most active Annona constituents. Annonaceous acetogenins are one of the most promising classes of natural products, owing to their potential antitumor activity. However, their neurotoxicity should not be underestimated. © 2017 New York Academy of Sciences.

  17. Ultrasound microbubble contrast agents: fundamentals and application to gene and drug delivery.

    PubMed

    Ferrara, Katherine; Pollard, Rachel; Borden, Mark

    2007-01-01

    This review offers a critical analysis of the state of the art of medical microbubbles and their application in therapeutic delivery and monitoring. When driven by an ultrasonic pulse, these small gas bubbles oscillate with a wall velocity on the order of tens to hundreds of meters per second and can be deflected to a vessel wall or fragmented into particles on the order of nanometers. While single-session molecular imaging of multiple targets is difficult with affinity-based strategies employed in some other imaging modalities, microbubble fragmentation facilitates such studies. Similarly, a focused ultrasound beam can be used to disrupt delivery vehicles and blood vessel walls, offering the opportunity to locally deliver a drug or gene. Clinical translation of these vehicles will require that current challenges be overcome, where these challenges include rapid clearance and low payload. The technology, early successes with drug and gene delivery, and potential clinical applications are reviewed.

  18. MRI-monitored intra-shunt local agent delivery of motexafin gadolinium: towards improving long-term patency of TIPS.

    PubMed

    Wang, Han; Zhang, Feng; Meng, Yanfeng; Zhang, Tong; Willis, Patrick; Le, Thomas; Soriano, Stephanie; Ray, Erik; Valji, Karim; Zhang, Guixiang; Yang, Xiaoming

    2013-01-01

    Transjugular intrahepatic portosystemic shunt (TIPS) has become an important and effective interventional procedure in treatment of the complications related to portal hypertension. Although the primary patency of TIPS has been greatly improved due to the clinical application of cover stent-grafts, the long-term patency is still suboptimal. This study was to investigate the feasibility of using magnetic resonance imaging (MRI)-monitored intra-shunt local agent delivery of motexafin gadolinium (MGd) into shunt-vein walls of TIPS. This new technique aimed to ultimately inhibit shuntstenosis of TIPS. Human umbilical vein smooth muscle cells (SMCs) were incubated with various concentrations of MGd, and then examed by confocal microscopy and T1-map MRI. In addition, the proliferation of MGd-treated cells was evaluated. For in vivo validation, seventeen pigs underwent TIPS. Before placement of the stent, an MGd/trypan-blue mixture was locally delivered, via a microporous balloon, into eleven shunt-hepatic vein walls under dynamic MRI monitoring, while trypan-blue only was locally delivered into six shunt-hepatic vein walls as serve as controls. T1-weighted MRI of the shunt-vein walls was achieved before- and at different time points after agent injections. Contrast-to-noise ratio (CNR) of the shunt-vein wall at each time-point was measured. Shunts were harvested for subsequent histology confirmation. In vitro studies confirmed the capability of SMCs in uptaking MGds in a concentration-dependent fashion, and demonstrated the suppression of cell proliferation by MGds as well. Dynamic MRI displayed MGd/blue penetration into the shunt-vein walls, showing significantly higher CNR of shunt-vein walls on post-delivery images than on pre-delivery images (49.5±9.4 vs 11.2±1.6, P<0.01), which was confirmed by histology. Results of this study indicate that MRI-monitored intra-shunt local MGd delivery is feasible and MGd functions as a potential therapeutic agent to inhibit the

  19. Discovery of potential antipsychotic agents possessing pro-cognitive properties.

    PubMed

    Lameh, Jelveh; McFarland, Krista; Ohlsson, Jorgen; Ek, Fredrik; Piu, Fabrice; Burstein, Ethan S; Tabatabaei, Ali; Olsson, Roger; Bradley, Stefania Risso; Bonhaus, Douglas W

    2012-03-01

    Current antipsychotic drug therapies for schizophrenia have limited efficacy and are notably ineffective at addressing the cognitive deficits associated with this disorder. The present study was designed to develop effective antipsychotic agents that would also ameliorate the cognitive deficits associated with this disease. In vitro studies comprised of binding and functional assays were utilized to identify compounds with the receptor profile that could provide both antipsychotic and pro-cognitive features. Antipsychotic and cognitive models assessing in vivo activity of these compounds included locomotor activity assays and novel object recognition assays. We developed a series of potential antipsychotic agents with a novel receptor activity profile comprised of muscarinic M(1) receptor agonism in addition to dopamine D(2) antagonism and serotonin 5-HT(2A) inverse agonism. Like other antipsychotic agents, these compounds reverse both amphetamine and dizocilpine-induced hyperactivity in animals. In addition, unlike other antipsychotic drugs, these compounds demonstrate pro-cognitive actions in the novel object recognition assay. The dual attributes of antipsychotic and pro-cognitive actions distinguish these compounds from other antipsychotic drugs and suggest that these compounds are prototype molecules in the development of novel pro-cognitive antipsychotic agents.

  20. Potential chitosan-coated alginate nanoparticles for ocular delivery of daptomycin.

    PubMed

    Costa, J R; Silva, N C; Sarmento, B; Pintado, M

    2015-06-01

    Daptomycin may offer an antibacterial alternative for the treatment of endophthalmitis caused by methicillin-resistant Staphylococcus aureus (MRSA) and other potential agents. In the present project, mucoadhesive chitosan-coated alginate (CS-ALG) nanoparticles are proposed as an effective delivery system for daptomycin permeation across ocular epithelia, with potential for the treatment of bacterial endophthalmitis. CS-ALG nanoparticles were prepared by ionotropic pre-gelation of an alginate core followed by chitosan polyelectrolyte complexation, and characterized regarding particle size, polydispersity, and zeta potential. The encapsulation efficiency was determined and antimicrobial activity was also tested after encapsulation of the antibiotic. Also, in vitro ocular permeability of free daptomycin and encapsulation into chitosan and CS-ALG nanoparticles was evaluated using ocular epithelial cell culture models. Formulated daptomycin-loaded CS-ALG nanoparticles were negatively charged, with a size range of 380-420 nm, suitable for ocular application. The encapsulation efficiency was between 79 and 92 %, with decreasing alginate:daptomycin mass ratios. The antibacterial activity of daptomycin against major microorganisms responsible for bacterial endophthalmitis was not affected by encapsulation into nanoparticles. Daptomycin permeability was up to 16 % (chitosan nanoparticles) and 9 % (CS-ALG nanoparticles) through corneal cell monolayer, and 18 % (chitosan nanoparticles) and 12 % (CS-ALG nanoparticles) for retinal cell monolayer after 4 h, demonstrating epithelial retention of the drug compared to free drug. The developed daptomycin-loaded CS-ALG nanoparticles seem to be an interesting and potential system for ocular daptomycin delivery and treatment of bacterial endophthalmitis.

  1. A pharmacological approach for the selection of potential anticancer agents.

    PubMed

    Double, John A

    2004-09-01

    Historically, the process of developing new anticancer agents was largely empirical. Today, because of improvements in our knowledge of the molecular processes involved in the development of cancer, the process of developing new agents is becoming more rational. Researchers from Cancer Research UK, the European Organisation for Research and Treatment of Cancer and the National Cancer Institute have shown that, by undertaking a pharmacological approach to the selection of potential anticancer agents, both meaningful antitumour data and an 80% reduction in animal usage can be obtained. It has also been demonstrated that a new pharmacological tool, the "hollow fibre system", in which tumour cells are grown in biocompatible fibres which are implanted into mice, can be used to produce meaningful antitumour data with pharmacodynamic endpoints. By increasing the amount of data that can be obtained from a single animal and opening up the possibility of eliminating the need for untreated control animals, the hollow fibre system has the potential to make a significant contribution to both reduction and refinement.

  2. Magnetic nanobeads as potential contrast agents for magnetic resonance imaging.

    PubMed

    Pablico-Lansigan, Michele H; Hickling, William J; Japp, Emily A; Rodriguez, Olga C; Ghosh, Anup; Albanese, Chris; Nishida, Maki; Van Keuren, Edward; Fricke, Stanley; Dollahon, Norman; Stoll, Sarah L

    2013-10-22

    Metal-oxo clusters have been used as building blocks to form hybrid nanomaterials and evaluated as potential MRI contrast agents. We have synthesized a biocompatible copolymer based on a water stable, nontoxic, mixed-metal-oxo cluster, Mn8Fe4O12(L)16(H2O)4, where L is acetate or vinyl benzoic acid, and styrene. The cluster alone was screened by NMR for relaxivity and was found to be a promising T2 contrast agent, with r1 = 2.3 mM(-1) s(-1) and r2 = 29.5 mM(-1) s(-1). Initial cell studies on two human prostate cancer cell lines, DU-145 and LNCap, reveal that the cluster has low cytotoxicity and may be potentially used in vivo. The metal-oxo cluster Mn8Fe4(VBA)16 (VBA = vinyl benzoic acid) can be copolymerized with styrene under miniemulsion conditions. Miniemulsion allows for the formation of nanometer-sized paramagnetic beads (~80 nm diameter), which were also evaluated as a contrast agent for MRI. These highly monodispersed, hybrid nanoparticles have enhanced properties, with the option for surface functionalization, making them a promising tool for biomedicine. Interestingly, both relaxivity measurements and MRI studies show that embedding the Mn8Fe4 core within a polymer matrix decreases r2 effects with little effect on r1, resulting in a positive T1 contrast enhancement.

  3. Intracarotid Delivery of Drugs: The Potential and the Pitfalls

    PubMed Central

    Joshi, Shailendra; Meyers, Phillip M.; Ornstein, Eugene

    2014-01-01

    The major efforts to selectively deliver drugs to the brain in the last decade have relied on smart molecular techniques to penetrate the blood brain barrier while intraarterial drug delivery has drawn relatively little attention. In the last decade there have been rapid advances in endovascular techniques. Modern endovascular procedures can permit highly targeted drug delivery by intracarotid route. Intracarotid drug delivery can be the primary route of drug delivery or it could be used to facilitate the delivery of smart-neuropharmaceuticals. There have been few attempts to systematically understand the kinetics of intracarotid drugs. Anecdotal data suggests that intracarotid drug delivery is effective in the treatment of cerebral vasospasm, thromboembolic strokes, and neoplasms. Neuroanesthesiologists are frequently involved in the care of such high-risk patients. Therefore, it is necessary to understand the applications of intracarotid drug delivery and the unusual kinetics of intracarotid drugs. PMID:18719453

  4. Transdermal drug delivery aided by an ultrasound contrast agent: an in vitro experimental study.

    PubMed

    Park, Donghee; Yoon, Jinhee; Park, Jingam; Jung, Byungjo; Park, Hyunjin; Seo, Jongbum

    2010-02-11

    Sonophoresis temporarily increases skin permeability such that medicine can be delivered transdermally. Cavitation is believed to be the predominant mechanism in sonophoresis. In this study, an ultrasound contrast agent (UCA) strategy was adopted instead of low frequency ultrasound to assure that cavitation occurred, and the efficacy of sonophoresis with UCA was quantitatively analyzed by optical measurements. The target drug used in this study was 0.1 % Definity(R) in 70% glycerol, which was delivered into porcine skin samples. Glycerol was used because it is an optical clearing agent, and the efficiency of glycerol delivery could be analyzed with optical measurements. The applied acoustic pressure was approximately 600 kPa at 1 MHz ultrasound with a 10% duty cycle for 60 minutes. Experimental results indicated that the measured relative contrast (RC) after sonophoresis with UCA was approximately 80% higher than RC after sonophoresis without UCA. In addition, the variance of RC was also reduced by more than 50% with the addition of a UCA. The use of a UCA appeared to increase cavitation, demonstrating that the use of a UCA can be effective in transdermal drug delivery (TDD).

  5. Transdermal Drug Delivery Aided by an Ultrasound Contrast Agent: An In Vitro Experimental Study

    PubMed Central

    Park, Donghee; Yoon, Jinhee; Park, Jingam; Jung, Byungjo; Park, Hyunjin; Seo, Jongbum

    2010-01-01

    Sonophoresis temporarily increases skin permeability such that medicine can be delivered transdermally. Cavitation is believed to be the predominant mechanism in sonophoresis. In this study, an ultrasound contrast agent (UCA) strategy was adopted instead of low frequency ultrasound to assure that cavitation occurred, and the efficacy of sonophoresis with UCA was quantitatively analyzed by optical measurements. The target drug used in this study was 0.1 % Definity® in 70% glycerol, which was delivered into porcine skin samples. Glycerol was used because it is an optical clearing agent, and the efficiency of glycerol delivery could be analyzed with optical measurements. The applied acoustic pressure was approximately 600 kPa at 1 MHz ultrasound with a 10% duty cycle for 60 minutes. Experimental results indicated that the measured relative contrast (RC) after sonophoresis with UCA was approximately 80% higher than RC after sonophoresis without UCA. In addition, the variance of RC was also reduced by more than 50% with the addition of a UCA. The use of a UCA appeared to increase cavitation, demonstrating that the use of a UCA can be effective in transdermal drug delivery (TDD). PMID:20448793

  6. Intratumoral infusion of fluid: estimation of hydraulic conductivity and implications for the delivery of therapeutic agents.

    PubMed Central

    Boucher, Y.; Brekken, C.; Netti, P. A.; Baxter, L. T.; Jain, R. K.

    1998-01-01

    We have developed a new technique to measure in vivo tumour tissue fluid transport parameters (hydraulic conductivity and compliance) that influence the systemic and intratumoral delivery of therapeutic agents. An infusion needle approximating a point source was constructed to produce a radially symmetrical fluid source in the centre of human tumours in immunodeficient mice. At constant flow, the pressure gradient generated in the tumour by the infusion of fluid (Evans blue-albumin in saline) was measured as a function of the radial position with micropipettes connected to a servo-null system. To evaluate whether the fluid infused was reabsorbed by blood vessels, infusions were also performed after circulatory arrest. In the colon adenocarcinoma LS174T with a spherically symmetrical distribution of Evans blue-albumin, the median hydraulic conductivity in vivo and after circulatory arrest at a flow rate of 0.1 microl min(-1) was, respectively, 1.7x10(-7) and 2.3x10(-7) cm2 mmHg(-1) s. Compliance estimates were 35 microl mmHg(-1) in vivo, and 100 microl mmHg(-1) after circulatory arrest. In the sarcoma HSTS 26T, hydraulic conductivity and compliance were not calculated because of the asymmetric distribution of the fluid infused. The technique will be helpful in identifying strategies to improve the intratumoral and systemic delivery of gene targeting vectors and other therapeutic agents. Images Figure 2 PMID:9836476

  7. Local drug delivery agents as adjuncts to endodontic and periodontal therapy

    PubMed Central

    Puri, K; Puri, N

    2013-01-01

    Abstract In the treatment of intracanal and periodontal infections, the local application of antibiotics and other therapeutic agents in the root canal or in periodontal pockets may be a promising approach to achieve sustained/controlled drug release, high antimicrobial activity and low systemic side effects. The conventional method for the elimination of subgingival microbial infection includes mechanical debridement, irrigation with antimicrobial agents or surgical access. But, the effectiveness of conventional nonsurgical treatment is limited by lack of accessibility to bacteria in deeper periodontal pockets, and/or does not completely eliminate intracanal microorganisms. Surgical intervention may be beneficial but cannot be done in all cases, medically compromised cases and also in patients not willing to be subjected to surgical therapy. Development of local drug delivery systems provides an answer to all such difficulties. This comprehensive review tries to cover the detailed information about the latest advances in the various local drug delivery systems, their indications, contraindications and their advantages over systemic drug therapy. PMID:24868252

  8. Templated high density lipoprotein nanoparticles as potential therapies and for molecular delivery.

    PubMed

    Damiano, Marina G; Mutharasan, R Kannan; Tripathy, Sushant; McMahon, Kaylin M; Thaxton, C Shad

    2013-05-01

    High density lipoproteins (HDLs) are dynamic natural nanoparticles best known for their role in cholesterol transport and the inverse correlation that exists between blood HDL levels and the risk of developing coronary heart disease. In addition, enhanced HDL-cholesterol uptake has been demonstrated in several human cancers. As such, the use of HDL as a therapeutic and as a vehicle for systemic delivery of drugs and as imaging agents is increasingly important. HDLs exist on a continuum from the secreted HDL-scaffolding protein, apolipoprotein A-1 (Apo A1), to complex, spherical "mature" HDLs. Aspects of HDL particles including their size, shape, and surface chemical composition are being recognized as critical to their diverse biological functions. Here we review HDL biology; strategies for synthesizing HDLs; data supporting the clinical use and benefit of directly administered HDL; a rationale for developing synthetic methods for spherical, mature HDLs; and, the potential to employ HDLs as therapies, imaging agents, and drug delivery vehicles. Importantly, methods that utilize nanoparticle templates to control synthetic HDL size, shape, and surface chemistry are highlighted. Copyright © 2012 Elsevier B.V. All rights reserved.

  9. Expanding the therapeutic potential of statins by means of nanotechnology enabled drug delivery systems.

    PubMed

    Romana, Bilquis; Batger, Mellissa; Prestidge, Clive A; Colombo, Gaia; Sonvico, Fabio

    2014-01-01

    Statins are effective lipid lowering agents traditionally used for the primary and secondary prevention of cardiovascular disease. Statins also exert a range of pleiotropic effects that make them attractive candidates for use in a wide range of disorders, in particular inflammatory and immune mediated conditions. However, the exploitation of such pleiotropic effects has been greatly hindered by poor bioavailability and adverse effects on muscles and the liver at higher doses. Nanotechnology is often suggested as the solution to this problem, as it enables an increased bioavailability of statins. Moreover, colloidal carriers can offer targeted drug delivery approaches that enable localised biological effects of statins, further reducing their potential for unwanted toxicity and adverse effects. This article reviews the available evidences for the increased potential of statin therapy when administered in nano-formulations such as nanocrystals, nanoparticles, liposomes, micelles and various nano-enabled devices.

  10. Reflux-free cannula for convection-enhanced high-speed delivery of therapeutic agents

    PubMed Central

    Krauze, Michal T.; Saito, Ryuta; Noble, Charles; Tamas, Matyas; Bringas, John; Park, John W.; Berger, Mitchel S.; Bankiewicz, Krystof

    2013-01-01

    Object Clinical application of the convection-enhanced delivery (CED) technique is currently limited by low infusion speed and reflux of the delivered agent. The authors developed and evaluated a new step-design cannula to overcome present limitations and to introduce a rapid, reflux-free CED method for future clinical trials. Methods The CED of 0.4% trypan blue dye was performed in agarose gel to test cannula needles for distribution and reflux. Infusion rates ranging from 0.5 to 50 μl/minute were used. Agarose gel findings were translated into a study in rats and then in cynomolgus monkeys (Macaca fascicularis) by using trypan blue and liposomes to confirm the efficacy of the reflux-free step-design cannula in vivo. Results of agarose gel studies showed reflux-free infusion with high flow rates using the step-design cannula. Data from the study in rats confirmed the agarose gel findings and also revealed increasing tissue damage at a flow rate above 5-μl/minute. Robust reflux-free delivery and distribution of liposomes was achieved using the step-design cannula in brains in both rats and nonhuman primates. Conclusions The authors developed a new step-design cannula for CED that effectively prevents reflux in vivo and maximizes the distribution of agents delivered in the brain. Data in the present study show reflux-free infusion with a constant volume of distribution in the rat brain over a broad range of flow rates. Reflux-free delivery of liposomes into nonhuman primate brain was also established using the cannula. This step-design cannula may allow reflux-free distribution and shorten the duration of infusion in future clinical applications of CED in humans. PMID:16304999

  11. Reflux-free cannula for convection-enhanced high-speed delivery of therapeutic agents.

    PubMed

    Krauze, Michal T; Saito, Ryuta; Noble, Charles; Tamas, Matyas; Bringas, John; Park, John W; Berger, Mitchel S; Bankiewicz, Krystof

    2005-11-01

    Clinical application of the convection-enhanced delivery (CED) technique is currently limited by low infusion speed and reflux of the delivered agent. The authors developed and evaluated a new step-design cannula to overcome present limitations and to introduce a rapid, reflux-free CED method for future clinical trials. The CED of 0.4% trypan blue dye was performed in agarose gel to test cannula needles for distribution and reflux. Infusion rates ranging from 0.5 to 50 microl/minute were used. Agarose gel findings were translated into a study in rats and then in cynomolgus monkeys (Macacafascicularis) by using trypan blue and liposomes to confirm the efficacy of the reflux-free step-design cannula in vivo. Results of agarose gel studies showed reflux-free infusion with high flow rates using the step-design cannula. Data from the study in rats confirmed the agarose gel findings and also revealed increasing tissue damage at a flow rate above 5-microl/minute. Robust reflux-free delivery and distribution of liposomes was achieved using the step-design cannula in brains in both rats and nonhuman primates. The authors developed a new step-design cannula for CED that effectively prevents reflux in vivo and maximizes the distribution of agents delivered in the brain. Data in the present study show reflux-free infusion with a constant volume of distribution in the rat brain over a broad range of flow rates. Reflux-free delivery of liposomes into nonhuman primate brain was also established using the cannula. This step-design cannula may allow reflux-free distribution and shorten the duration of infusion in future clinical applications of CED in humans.

  12. Alginate nanoparticles protect ferrous from oxidation: Potential iron delivery system.

    PubMed

    Katuwavila, Nuwanthi P; Perera, A D L C; Dahanayake, Damayanthi; Karunaratne, V; Amaratunga, Gehan A J; Karunaratne, D Nedra

    2016-11-20

    A novel, efficient delivery system for iron (Fe(2+)) was developed using the alginate biopolymer. Iron loaded alginate nanoparticles were synthesized by a controlled ionic gelation method and was characterized with respect to particle size, zeta potential, morphology and encapsulation efficiency. Successful loading was confirmed with Fourier Transform Infrared spectroscopy and Thermogravimetric Analysis. Electron energy loss spectroscopy study corroborated the loading of ferrous into the alginate nanoparticles. Iron encapsulation (70%) was optimized at 0.06% Fe (w/v) leading to the formation of iron loaded alginate nanoparticles with a size range of 15-30nm and with a negative zeta potential (-38mV). The in vitro release studies showed a prolonged release profile for 96h. Release of iron was around 65-70% at pH of 6 and 7.4 whereas it was less than 20% at pH 2.The initial burst release upto 8h followed zero order kinetics at all three pH values. All the release profiles beyond 8h best fitted the Korsmeyer-Peppas model of diffusion. Non Fickian diffusion was observed at pH 6 and 7.4 while at pH 2 Fickian diffusion was observed. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Hypoglycemic agents and potential anti-inflammatory activity

    PubMed Central

    Kothari, Vishal; Galdo, John A; Mathews, Suresh T

    2016-01-01

    Current literature shows an association of diabetes and secondary complications with chronic inflammation. Evidence of these immunological changes include altered levels of cytokines and chemokines, changes in the numbers and activation states of various leukocyte populations, apoptosis, and fibrosis during diabetes. Therefore, treatment of diabetes and its complications may include pharmacological strategies to reduce inflammation. Apart from anti-inflammatory drugs, various hypoglycemic agents have also been found to reduce inflammation that could contribute to improved outcomes. Extensive studies have been carried out with thiazolidinediones (peroxisome proliferator-activated receptor-γ agonist), dipeptidyl peptidase-4 inhibitors, and metformin (AMP-activated protein kinase activator) with each of these classes of compounds showing moderate-to-strong anti-inflammatory action. Sulfonylureas and alpha glucosidase inhibitors appeared to exert modest effects, while the injectable agents, insulin and glucagon-like peptide-1 receptor agonists, may improve secondary complications due to their anti-inflammatory potential. Currently, there is a lack of clinical data on anti-inflammatory effects of sodium–glucose cotransporter type 2 inhibitors. Nevertheless, for all these glucose-lowering agents, it is essential to distinguish between anti-inflammatory effects resulting from better glucose control and effects related to intrinsic anti-inflammatory actions of the pharmacological class of compounds. PMID:27114714

  14. Intranasal delivery bypasses the blood-brain barrier to target therapeutic agents to the central nervous system and treat neurodegenerative disease.

    PubMed

    Hanson, Leah R; Frey, William H

    2008-12-10

    Intranasal delivery provides a practical, non-invasive method of bypassing the blood-brain barrier (BBB) to deliver therapeutic agents to the brain and spinal cord. This technology allows drugs that do not cross the BBB to be delivered to the central nervous system within minutes. It also directly delivers drugs that do cross the BBB to the brain, eliminating the need for systemic administration and its potential side effects. This is possible because of the unique connections that the olfactory and trigeminal nerves provide between the brain and external environment. Intranasal delivery does not necessarily require any modification to therapeutic agents. A wide variety of therapeutics, including both small molecules and macromolecules, can be targeted to the olfactory system and connected memory areas affected by Alzheimer's disease. Using the intranasal delivery system, researchers have reversed neurodegeneration and rescued memory in a transgenic mouse model of Alzheimer's disease. Intranasal insulin-like growth factor-I, deferoxamine, and erythropoietin have been shown to protect the brain against stroke in animal models. Intranasal delivery has been used to target the neuroprotective peptide NAP to the brain to treat neurodegeneration. Intranasal fibroblast growth factor-2 and epidermal growth factor have been shown to stimulate neurogenesis in adult animals. Intranasal insulin improves memory, attention, and functioning in patients with Alzheimer's disease or mild cognitive impairment, and even improves memory and mood in normal adult humans. This new method of delivery can revolutionize the treatment of Alzheimer's disease, stroke, and other brain disorders.

  15. A feeding protocol for delivery of agents to assess development in Varroa mites

    PubMed Central

    2017-01-01

    A novel feeding protocol for delivery of bio-active agents to Varroa mites was developed by providing mites with honey bee larva hemolymph supplemented with cultured insect cells and selected materials delivered on a fibrous cotton substrate. Mites were starved, fed on treated hemolymph to deliver selected agents and then returned to bee larvae. Transcript levels of two reference genes, actin and glyceraldehyde 3-phosphate dehydrogenase (GAPDH), as well as for nine selected genes involved in reproductive processes showed that the starvation and feeding protocol periods did not pose a high level of stress to the mites as transcript levels remained comparable between phoretic mites and those completing the protocol. The feeding protocol was used to deliver molecules such as hormone analogs or plasmids. Mites fed with Tebufenozide, an ecdysone analog, had higher transcript levels of shade than untreated or solvent treated mites. In order to extend this feeding protocol, cultured insect cells were incorporated to a final ratio of 1 part cells and 2 parts hemolymph. Although supplementation with Bombyx mori Bm5 cells increased the amount of hemolymph consumed per mite, there was a significant decrease in the percentage of mites that fed and survived. On the other hand, Drosophila melanogaster S2 cells reduced significantly the percentage of mites that fed and survived as well as the amount of hemolymph consumed. The feeding protocol provides a dynamic platform with which to challenge the Varroa mite to establish efficacy of control agents for this devastating honey bee pest. PMID:28448606

  16. A feeding protocol for delivery of agents to assess development in Varroa mites.

    PubMed

    Cabrera, Ana R; Shirk, Paul D; Teal, Peter E A

    2017-01-01

    A novel feeding protocol for delivery of bio-active agents to Varroa mites was developed by providing mites with honey bee larva hemolymph supplemented with cultured insect cells and selected materials delivered on a fibrous cotton substrate. Mites were starved, fed on treated hemolymph to deliver selected agents and then returned to bee larvae. Transcript levels of two reference genes, actin and glyceraldehyde 3-phosphate dehydrogenase (GAPDH), as well as for nine selected genes involved in reproductive processes showed that the starvation and feeding protocol periods did not pose a high level of stress to the mites as transcript levels remained comparable between phoretic mites and those completing the protocol. The feeding protocol was used to deliver molecules such as hormone analogs or plasmids. Mites fed with Tebufenozide, an ecdysone analog, had higher transcript levels of shade than untreated or solvent treated mites. In order to extend this feeding protocol, cultured insect cells were incorporated to a final ratio of 1 part cells and 2 parts hemolymph. Although supplementation with Bombyx mori Bm5 cells increased the amount of hemolymph consumed per mite, there was a significant decrease in the percentage of mites that fed and survived. On the other hand, Drosophila melanogaster S2 cells reduced significantly the percentage of mites that fed and survived as well as the amount of hemolymph consumed. The feeding protocol provides a dynamic platform with which to challenge the Varroa mite to establish efficacy of control agents for this devastating honey bee pest.

  17. Drug Delivery Innovations for Enhancing the Anticancer Potential of Vitamin E Isoforms and Their Derivatives

    PubMed Central

    Neophytou, Christiana M.; Constantinou, Andreas I.

    2015-01-01

    Vitamin E isoforms have been extensively studied for their anticancer properties. Novel drug delivery systems (DDS) that include liposomes, nanoparticles, and micelles are actively being developed to improve Vitamin E delivery. Furthermore, several drug delivery systems that incorporate Vitamin E isoforms have been synthesized in order to increase the bioavailability of chemotherapeutic agents or to provide a synergistic effect. D-alpha-tocopheryl polyethylene glycol succinate (Vitamin E TPGS or TPGS) is a synthetic derivative of natural alpha-tocopherol which is gaining increasing interest in the development of drug delivery systems and has also shown promising anticancer effect as a single agent. This review provides a summary of the properties and anticancer effects of the most potent Vitamin E isoforms and an overview of the various formulations developed to improve their efficacy, with an emphasis on the use of TPGS in drug delivery approaches. PMID:26137487

  18. Design of multivalent galactosyl carborane as a targeting specific agent for potential application to boron neutron capture therapy.

    PubMed

    Lai, Chian-Hui; Lin, Yu-Chuan; Chou, Fong-In; Liang, Chien-Fu; Lin, En-Wei; Chuang, Yung-Jen; Lin, Chun-Cheng

    2012-01-14

    A multivalent galactosyl carborane derivative 10 (dendritic glyco-borane, DGB) was synthesized and demonstrated as a potential cell-targeting agent in BNCT with HepG2 cells. DGB 10 improved the delivery of boron to HepG2 cells and neutron irradiation data show DGB 10 with ten-fold improvement at killing the HepG2 cells over BSH. This journal is © The Royal Society of Chemistry 2012

  19. 1,3,4-oxadiazole derivatives as potential biological agents.

    PubMed

    Sun, Juan; Makawana, Jigar A; Zhu, Hai-Liang

    2013-10-01

    The synthesis of novel compound libraries along with screening is a rapid and effective approach for the discovery of potential chemical agents, and it becomes an important method in pharmaceutical chemistry research. 1,3,4- oxadiazole derivatives as the typical heterocyclic compounds, exhibit a broad spectrum of biological activities and vital leading compounds for the development of chemical drugs. Herein, we focus on the synthesis and screening of novel 1,3,4-oxadiazoles derivatives with antimicrobial, antitumor or antiviral activities during the past decade. In this review, we discussed the synthetic development of 1,3,4-oxadiazoles derivatives, and also the relevant bioactivity and their prospects as the potential chemical drugs.

  20. Enkephalinase inhibitors: potential agents for the management of pain.

    PubMed

    Thanawala, V; Kadam, V J; Ghosh, R

    2008-10-01

    Management of acute and chronic pain has always been a key area of clinical research. Enkephalinase inhibitors (EIs) seem to be promising as therapeutic agents having antinociceptive action. They additionally possess anticraving, antidiarrhoeal and antidepressant actions. The antinociceptive action of EIs has been reported for over a decade however, their therapeutic potential is yet to be effectively explored. EIs may be broadly classified as endogenous and those that are obtained synthetically. Endogenous EIs include peptides like spinorphin and opiorphin. And compounds like RB 101, RB 120, RB 3007 constitute the synthetically obtained EIs. Endogenous and synthetic inhibitors enkephalin degrading enzymes have been studied in vivo using standard animal models. The potential EI targets appear to be APN (Aminopeptidase N), NEP (Neutral endopeptidase), DPP-III (Dipeptidyl peptidase). EIs possess the advantage that they lack the opioid side effects. This article reviews the mechanisms by which EIs act and elucidates the pathways involved.

  1. Turning on the Radio: Epigenetic Inhibitors as Potential Radiopriming Agents

    PubMed Central

    Oronsky, Bryan; Scicinski, Jan; Kim, Michelle M.; Cabrales, Pedro; Salacz, Michael E.; Carter, Corey A.; Oronsky, Neil; Lybeck, Harry; Lybeck, Michelle; Larson, Christopher; Reid, Tony R.; Oronsky, Arnold

    2016-01-01

    First introduced during the late 1800s, radiation therapy is fundamental to the treatment of cancer. In developed countries, approximately 60% of all patients receive radiation therapy (also known as the sixty percenters), which makes radioresistance in cancer an important and, to date, unsolved, clinical problem. Unfortunately, the therapeutic refractoriness of solid tumors is the rule not the exception, and the ubiquity of resistance also extends to standard chemotherapy, molecularly targeted therapy and immunotherapy. Based on extrapolation from recent clinical inroads with epigenetic agents to prime refractory tumors for maximum sensitivity to concurrent or subsequent therapies, the radioresistant phenotype is potentially reversible, since aberrant epigenetic mechanisms are critical contributors to the evolution of resistant subpopulations of malignant cells. Within the framework of a syllogism, this review explores the emerging link between epigenetics and the development of radioresistance and makes the case that a strategy of pre- or co-treatment with epigenetic agents has the potential to, not only derepress inappropriately silenced genes, but also increase reactive oxygen species production, resulting in the restoration of radiosensitivity. PMID:27384589

  2. Artocarpus plants as a potential source of skin whitening agents.

    PubMed

    Arung, Enos Tangke; Shimizu, Kuniyoshi; Kondo, Ryuichiro

    2011-09-01

    Artocarpus plants have been a focus of constant attention due to the potential for skin whitening agents. In the in vitro experiment, compounds from the Artocarpus plants, such as artocarpanone, norartocarpetin, artocarpesin, artogomezianol, andalasin, artocarbene, and chlorophorin showed tyrosinase inhibitory activity. Structure-activity investigations revealed that the 4-substituted resorcinol moiety in these compounds was responsible for their potent inhibitory activities on tyrosinase. In the in vitro assay, using B16 melanoma cells, the prenylated polyphenols isolated from Artocarpus plants, such as artocarpin, cudraflavone C, 6-prenylapigenin, kuwanon C, norartocarpin, albanin A, cudraflavone B, and brosimone I showed potent inhibitory activity on melanin formation. Structure-activity investigations revealed that the introduction of an isoprenoid moiety to a non-isoprenoid-substituted polyphenol enhanced the inhibitory activity of melanin production in B16 melanoma cells. In the in vivo investigation, the extract of the wood of Artocarpus incisus and a representative isolated compound from it, artocarpin had a lightening effect on the skin of guinea pigs' backs. Other in vivo experiments using human volunteers have shown that water extract of Artocarpus lakoocha reduced the melanin formation in the skin of volunteers. These results indicate that the extracts of Artocarpus plants are potential sources for skin whitening agents.

  3. Ultrasound Delivery of an Anti-Aβ Therapeutic Agent to the Brain in a Mouse Model of Alzheimer's Disease

    NASA Astrophysics Data System (ADS)

    Jordão, Jessica F.; Ayala-Grosso, Carlos A.; Chopra, Rajiv; McLaurin, JoAnne; Aubert, Isabelle; Hynynen, Kullervo

    2009-04-01

    Plaques composed of amyloid-beta (Aβ) peptides represent a pathological hallmark in the brain of patients with Alzheimer's disease. Aβ oligomers are considered cytotoxic and several therapeutic approaches focus on reducing Aβ load in the brain of Alzheimer's patients. The efficacy of most anti-Aβ agents is significantly limited because they do not cross the blood-brain-barrier. Innovative technologies capable of enhancing the permeability of the blood-brain barrier, thereby allowing entry of therapeutic agents into the brain, show great promise in circumventing this problem. The application of low-intensity focused ultrasound in the presence of an ultrasound contrast agent causes localized and transient permeability of the blood-brain barrier. We demonstrate the value of this technology for the delivery of anti-Aβ antibodies to the brain of TgCRND8 mice, a mouse model of Alzheimer's disease exhibiting Aβ plaques. BAM-10, an anti-Aβ antibody, was injected into the tail vein simultaneously with exposure to MRI-guided, low-intensity focused ultrasound (FUS) to one hemisphere of TgCNRD8 mice. Four hours after treatment, antibodies were detected at significant amounts only in the brain of mice receiving FUS in addition to BAM-10. This data provides a proof-of-concept that FUS allows anti-Aβ therapeutics to efficiently enter the brain and target Aβ plaques. Four days following a single treatment with BAM-10 and MRI-guided FUS, a significant decrease in the number of Aβ plaques on the side of the treated hemisphere was observed in TgCRND8 mice. In conclusion low-intensity, focused ultrasound is effective in delivering Aβ antibodies to the brain. This technology has the potential to enhance current anti-Aβ treatments by allowing increased exposure of amyloid plaques to treatment agents.

  4. Simultaneous Delivery of Multiple Antibacterial Agents from Additively Manufactured Porous Biomaterials to Fully Eradicate Planktonic and Adherent Staphylococcus aureus.

    PubMed

    Bakhshandeh, S; Gorgin Karaji, Z; Lietaert, K; Fluit, A C; Boel, C H E; Vogely, H C; Vermonden, T; Hennink, W E; Weinans, H; Zadpoor, A A; Amin Yavari, S

    2017-08-09

    Implant-associated infections are notoriously difficult to treat and may even result in amputation and death. The first few days after surgery are the most critical time to prevent those infections, preferably through full eradication of the micro-organisms entering the body perioperatively. That is particularly important for patients with a compromised immune system such as orthopedic oncology patients, as they are at higher risk for infection and complications. Full eradication of bacteria is, especially in a biofilm, extremely challenging due to the toxicity barrier that prevents delivery of high doses of antibacterial agents. This study aimed to use the potential synergistic effects of multiple antibacterial agents to prevent the use of toxic levels of these agents and achieve full eradication of planktonic and adherent bacteria. Silver ions and vancomycin were therefore simultaneously delivered from additively manufactured highly porous titanium implants with an extremely high surface area incorporating a bactericidal coating made from chitosan and gelatin applied by electrophoretic deposition (EPD). The presence of the chitosan/gelatin (Ch+Gel) coating, Ag, and vancomycin (Vanco) was confirmed by X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR). The release of vancomycin and silver ions continued for at least 21 days as measured by inductively coupled plasma (ICP) and UV-spectroscopy. Antibacterial behavior against Staphylococcus aureus, both planktonic and in biofilm, was evaluated for up to 21 days. The Ch+Gel coating showed some bactericidal behavior on its own, while the loaded hydrogels (Ch+Gel+Ag and Ch+Gel+Vanco) achieved full eradication of both planktonic and adherent bacteria without causing significant levels of toxicity. Combining silver and vancomycin improved the release profiles of both agents and revealed a synergistic behavior that further increased the bactericidal effects.

  5. Cyclen-based lipidic oligomers as potential gene delivery vehicles.

    PubMed

    Yi, Wen-Jing; Zhang, Qin-Fang; Zhang, Ji; Liu, Qiang; Ren, Laifeng; Chen, Qian-Ming; Guo, Liandi; Yu, Xiao-Qi

    2014-03-01

    A series of cyclen-based linear oligomers bearing hydrophobic long chains (lipopolymers Cy-LC, where Cy and LC represent cyclen-based linear backbone and hydrophobic long chain substituents, respectively) were designed and synthesized. The effects of type and degree of substitution (DS) of hydrophobic long chains on the transfection efficiency were systematically studied. The nitrogen atoms with relatively strong basicity on the cyclen ensure their good DNA binding ability, which was confirmed by gel retardation and ethidium bromide exclusion assays. Lipopolyplexes could be formed as nanoparticles with suitable sizes and zeta potentials for gene transfection. In vitro gene delivery experiments revealed that the linoleic acid (LIN) substituted material Cy-LIN has better transfection efficiency than 25 kDa polyethylenimine in the absence or in the presence of serum. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and hemolysis assays showed low cytotoxicity and good biocompatibility of the lipopolyplexes. Fluorescent labeled DNA was used to study the cellular uptake and intracellular distribution of transfected DNA. Flow cytometry results suggested that a long chain is necessary for efficient cellular uptake, and images from confocal laser scanning microscopy showed that after 4h transfection, most of the fluorescent labeled DNA accumulated in the perinuclear region, which was required for efficient gene expression. Moreover, it was also found that the DS of the hydrophobic moiety can adjust the balance between DNA binding ability and dissociation of polyplexes, significantly affecting the transfection efficiency.

  6. Solid lipid nanoparticles (SLN) of tretinoin: potential in topical delivery.

    PubMed

    Shah, Kumar A; Date, Abhijit A; Joshi, Medha D; Patravale, Vandana B

    2007-12-10

    The objective of this investigation was to develop solid lipid nanoparticles (SLN) of tretinoin (TRE) with the help of facile and simple emulsification-solvent diffusion (ESD) technique and to evaluate the viability of an SLN based gel in improving topical delivery of TRE. The feasibility of fabricating SLN of TRE by the ESD method was successfully demonstrated in this investigation. The developed SLN were characterized for particle size, polydispersity index, entrapment efficiency of TRE and morphology. Studies were carried out to evaluate the ability of SLN in improving the photostability of TRE as compared to TRE in methanol. Encapsulation of TRE in SLN resulted in a significant improvement in its photostability in comparison to methanolic TRE solution and also prevented its isomerization. Furthermore, the skin irritation studies carried out on rabbits showed that SLN based TRE gel is significantly less irritating to skin as compared to marketed TRE cream and clearly indicated its potential in improving the skin tolerability of TRE. In vitro permeation studies through rat skin indicated that an SLN based TRE gel has permeation profile comparable to that of the marketed TRE cream.

  7. Carbon nanotubes buckypapers for potential transdermal drug delivery.

    PubMed

    Schwengber, Alex; Prado, Héctor J; Zilli, Darío A; Bonelli, Pablo R; Cukierman, Ana L

    2015-12-01

    Drug loaded buckypapers based on different types of carbon nanotubes (CNTs) were prepared and characterized in order to evaluate their potentialities for the design of novel transdermal drug delivery systems. Lab-synthesized CNTs as well as commercial samples were employed. Clonidine hydrochloride was used as model drug, and the influence of composition of the drug loaded buckypapers and processing variables on in vitro release profiles was investigated. To examine the influence of the drug nature the evaluation was further extended to buckypapers prepared with flurbiprofen and one type of CNTs, their selection being based on the results obtained with the former drug. Scanning electronic microscopy images indicated that the model drugs were finely dispersed on the CNTs. Differential scanning calorimetry, and X-ray diffraction pointed to an amorphous state of both drugs in the buckypapers. A higher degree of CNT-drug superficial interactions resulted in a slower release of the drug. These interactions were in turn affected by the type of CNTs employed (single wall or multiwall CNTs), their functionalization with hydroxyl or carboxyl groups, the chemical structure of the drug, and the CNT:drug mass ratio. Furthermore, the application of a second layer of drug free CNTs on the loaded buckypaper, led to decelerate the drug release and to reduce the burst effect.

  8. Targeting ferritin receptors for the selective delivery of imaging and therapeutic agents to breast cancer cells

    NASA Astrophysics Data System (ADS)

    Geninatti Crich, S.; Cadenazzi, M.; Lanzardo, S.; Conti, L.; Ruiu, R.; Alberti, D.; Cavallo, F.; Cutrin, J. C.; Aime, S.

    2015-04-01

    In this work the selective uptake of native horse spleen ferritin and apoferritin loaded with MRI contrast agents has been assessed in human breast cancer cells (MCF-7 and MDA-MB-231). The higher expression of L-ferritin receptors (SCARA5) led to an enhanced uptake in MCF-7 as shown in T2 and T1 weighted MR images, respectively. The high efficiency of ferritin internalization in MCF-7 has been exploited for the simultaneous delivery of curcumin, a natural therapeutic molecule endowed with antineoplastic and anti-inflammatory action, and the MRI contrast agent Gd-HPDO3A. This theranostic system is able to treat selectively breast cancer cells over-expressing ferritin receptors. By entrapping in apoferritin both Gd-HPDO3A and curcumin, it was possible to deliver a therapeutic dose of 167 μg ml-1 (as calculated by MRI) of this natural drug to MCF-7 cells, thus obtaining a significant reduction of cell proliferation.In this work the selective uptake of native horse spleen ferritin and apoferritin loaded with MRI contrast agents has been assessed in human breast cancer cells (MCF-7 and MDA-MB-231). The higher expression of L-ferritin receptors (SCARA5) led to an enhanced uptake in MCF-7 as shown in T2 and T1 weighted MR images, respectively. The high efficiency of ferritin internalization in MCF-7 has been exploited for the simultaneous delivery of curcumin, a natural therapeutic molecule endowed with antineoplastic and anti-inflammatory action, and the MRI contrast agent Gd-HPDO3A. This theranostic system is able to treat selectively breast cancer cells over-expressing ferritin receptors. By entrapping in apoferritin both Gd-HPDO3A and curcumin, it was possible to deliver a therapeutic dose of 167 μg ml-1 (as calculated by MRI) of this natural drug to MCF-7 cells, thus obtaining a significant reduction of cell proliferation. Electronic supplementary information (ESI) available: Competition studies with free apoferritin, Fig. S1; APO-FITC intracellular distribution by

  9. The potential of liposomes as dental drug delivery systems.

    PubMed

    Nguyen, Sanko; Hiorth, Marianne; Rykke, Morten; Smistad, Gro

    2011-01-01

    The potential of liposomes as a drug delivery system for use in the oral cavity has been investigated. Specifically targeting for the teeth, the in vitro adsorption of charged liposomal formulations to hydroxyapatite (HA), a common model substance for the dental enamel, has been conducted. The experiments were performed in human parotid saliva to simulate oral-like conditions. It was observed, however, that precipitation occurred in tubes containing DPPC/DPTAP or DPPC/DPPG-liposomes in parotid saliva with no HA present, indicating that constituents of parotid saliva reacted with the liposomes. The aggregation reactions of liposome-parotid saliva mixtures were examined by turbidimetry and by atomic force microscopy. Negatively charged DPPC/DPPS and DPPC/PI-liposomes were additionally included in these experiments. The initial turbidity of positive DPPC/DPTAP-liposomes in parotid saliva was very high, but decreased markedly after 30 min. AFM images showed large aggregates of micelle-like globules known to be present in saliva. The turbidity of the various negatively charged liposome and parotid saliva mixtures stayed relatively constant throughout the measuring time; however, their initial turbidities were different; mixtures with DPPC/DPPG-liposomes were the most turbid and DPPC/DPPA-liposomes the least. Pyrophosphate (PP) was added to the various liposome-parotid saliva mixtures to examine the effect of Ca(2+) on the interactions. The effect of PP treatment of the negatively charged liposome-parotid saliva mixtures was most pronounced with DPPC/DPPG-liposome mixtures where it caused a sudden drop in turbidity. For positive DPPC/DPTAP liposome and parotid saliva mixtures, the effect of PP was minimal. These experiments showed that saliva constituents may interact with liposomes. An appropriate liposomal drug delivery system intended for use in the oral cavity seems to be dependent on the liposomal formulation. Based on the present results, negatively charged DPPC

  10. Development and Optimization of a Doxorubicin Loaded Poly Lactic Acid Contrast Agent for Ultrasound Directed Drug Delivery

    PubMed Central

    Eisenbrey, J.R.; Burstein, O. Mualem; Kambhampati, R.; Forsberg, F.; Liu, J-B.; Wheatley, M.A.

    2010-01-01

    An echogenic, intravenous drug delivery platform is proposed in which an encapsulated chemotherapeutic can travel to a desired location and drug delivery can be triggered using external, focused ultrasound at the area of interest. Three methods of loading poly lactic acid (PLA) shelled ultrasound contrast agents (UCA) with doxorubicin are presented. Effects on encapsulation efficiency, in vitro enhancement, stability, particle size, morphology and release during UCA rupture are compared by loading method and drug concentration. An agent containing doxorubicin within the shell was selected as an ideal candidate for future hepatocellular carcinoma studies. The agent achieved a maximal drug load of 6.2 mg Dox/g PLA with an encapsulation efficiency of 20.5%, showed a smooth surface morphology and tight size distribution (poly dispersity index = 0.309) with a peak size of 1865 nm. Acoustically, the agent provided 19 dB of enhancement in vitro at a dosage of 10 µg/ml, with a half life of over 15 mins. In vivo, the agent provided ultrasound enhancement of 13.4 ± 1.6 dB within the ascending aorta of New Zealand rabbits at a dose of 0.15 ml/kg. While the drug-incorporated agent is thought to be well suited for future drug delivery experiments, this study has shown that agent properties can be tailored for specific applications based on choice of drug loading method. PMID:20060024

  11. Particle interactions of polyvinylpyrrolidone-coated iron oxide particles as magnetic drug delivery agents

    NASA Astrophysics Data System (ADS)

    İşçi, Sevim; İşçi, Yavuz; Bekaroğlu, Maide Gökçe

    2017-08-01

    Iron oxide particles have been recently researched for the potential applications of targeted drug delivery due to their magnetic properties. The surfaces of the iron oxide particles must be modified to reduce the toxicity and to load the drug to the particles. Biopolymers are good surface modifiers of colloidal particles such as iron oxide particles. The degree of surface coverage of the colloidal iron oxide particles affects the stability, toxicity, magnetic properties and drug loading efficiency. In this study, the interactions of iron oxide (Fe3O4) particles and PVP were determined according to the colloidal properties. The proper concentration of PVP for the whole coverage of the iron oxide particles was found for the possible magnetic drug delivery applications by controlling the colloidal properties of the dispersions. The magnetic properties and toxicity of the fully covered bioiron oxide was also determined for possible applications.

  12. MAD (Multi-Agent-Delivery) Nanolayer: Delivering Multiple Therapeutics from Hierarchical Assembled Surface Coatings

    PubMed Central

    Kim, Byeong-Su; Smith, Renée C.; Poon, Zhiyong; Hammond, Paula T.

    2014-01-01

    We present the hydrolytically degradable polymeric multilayer films that can co-deliver multiple therapeutics of differing chemical characteristics (charged biomacromolecules and neutral hydrophobic small molecules) from a surface. This multi-agent-delivery (MAD) nanolayer system integrates the hydrolytically degradable poly(β-amino ester) as a structural component to control the degradation of the multilayers to release active therapeutic macromolecules, as well as hydrophobic drugs imbedded within amphiphilic block copolymer micellar carriers within layer-by-layer (LbL) films, which would otherwise be difficult to include within the multilayers. By varying the anionic therapeutic agents (heparin and dextran sulfate) within the multilayer, we examine how different structural components can be used to control the release kinetics of multiple therapeutics from MAD nanolayers. Controlled release profiles and the in vitro efficacy of the MAD nanolayers in suppressing the growth of human smooth muscle cell lines were evaluated. The dual delivery of a charged macromolecular heparin and a small hydrophobic drug, paclitaxel, is found to be synergistic and beneficial toward effective therapeutic activity. Furthermore, we compared the classical dipping method we employed here with an automated spray-LbL technique. Spray-LbL significantly facilitates film processing time while preserving the characteristic release profiles of the MAD nanolayers. With the highly versatile and tunable nature of LbL assembly, we anticipate that MAD nanolayers can provide a unique platform for delivering multiple therapeutics from macromolecular to small molecules with distinct release profiles for applications in biological and biomedical surface coatings. PMID:19630389

  13. Graphene nanoribbons as a drug delivery agent for lucanthone mediated therapy of glioblastoma multiforme

    DOE PAGES

    Chowdhury, Sayan Mullick; Surhland, Cassandra; Sanchez, Zina; ...

    2014-08-13

    We report use of PEG-DSPE coated oxidized graphene nanoribbons (O-GNR-PEG-DSPE) as agent for delivery of anti-tumor drug Lucanthone (Luc) into Glioblastoma Multiformae (GBM) cells targeting base excision repair enzyme APE-1 (Apurinic endonuclease-1). Lucanthone, an endonuclease inhibitor of APE-1, was loaded onto O-GNR-PEG-DSPEs using a simple non-covalent method. We found its uptake by GBM cell line U251 exceeding 67% and 60% in APE-1-overexpressing U251, post 24 hours (h). However, their uptake was ~38% and 29% by MCF-7 and rat glial progenitor cells (CG-4), respectively. TEM analysis of U251 showed large aggregates of O-GNR-PEG-DSPE in vesicles. Luc-O-GNR-PEG-DSPE was significantly toxic to U251more » but showed little / no toxicity when exposed to MCF-7/CG-4 cells. This differential uptake effect can be exploited to use O-GNR-PEG-DSPEs as a vehicle for Luc delivery to GBM, while reducing nonspecific cytotoxicity to the surrounding healthy tissue. In conclusion, cell death in U251 was necrotic, probably due to oxidative degradation of APE-1.« less

  14. Bifunctional Coupling Agents for Radiolabeling of Biomolecules and Target-Specific Delivery of Metallic Radionuclides

    PubMed Central

    Liu, Shuang

    2008-01-01

    Receptor-based radiopharmaceuticals are of great current interest in early molecular imaging and radiotherapy of cancers, and provide a unique tool for target-specific delivery of radionuclides to the diseased tissues. In general, a target-specific radiopharmaceutical can be divided into four parts: targeting biomolecule (BM), pharmacokinetic modifying (PKM) linker, bifunctional coupling or chelating agent (BFC), and radionuclide. The targeting biomolecule serves as a “carrier” for specific delivery of the radionuclide. PKM linkers are used to modify radiotracer excretion kinetics. BFC is needed for radiolabeling of biomolecules with a metallic radionuclide. Different radiometals have significant difference in their coordination chemistry, and require BFCs with different donor atoms and chelator frameworks. Since the radiometal chelate can have a significant impact on physical and biological properties of the target-specific radiopharmaceutical, its excretion kinetics can be altered by modifying the coordination environment with various chelators or coligand, if needed. This review will focus on the design of BFCs and their coordination chemistry with technetium, copper, gallium, indium, yttrium and lanthanide radiometals. PMID:18538888

  15. Self-assembled nanoplatform for targeted delivery of chemotherapy agents via affinity-regulated molecular interactions.

    PubMed

    Park, Spencer; Kang, Sungkwon; Veach, Alexander J; Vedvyas, Yogindra; Zarnegar, Rasa; Kim, Ju-Young; Jin, Moonsoo M

    2010-10-01

    Site-specific delivery of drugs while minimizing unwanted distribution has been one of the pursued goals in cancer therapy. In this endeavor, we have developed targeted polymeric nanoparticles called amphiphilic urethane acrylate nonionomer (UAN) for encapsulation of diverse water-insoluble drugs and diagnostic agents, as well as for simple and reproducible surface conjugation of targeting ligands. Using monoclonal antibodies or lymphocyte function-associated antigen-1 (LFA-1) I domain engineered for varying affinities to intercellular adhesion molecule (ICAM)-1, we were able to deliver UAN nanoparticles to human cancer cells with the efficiency dependent on the strength of the molecular interactions and the degree of ICAM-1 expression on cell surface. Compared to non-specific uptake of free drugs, targeted delivery of UAN nanoparticles carrying equal amount of drugs produced more potent cytotoxicity. Notably, without the targeting ligands attached, UAN nanoparticles were largely precluded from non-specific uptake by the cells, resulting in much lower toxicity. The versatility of our UAN nanoparticles in both payload encapsulation and presentation of targeting ligands may facilitate developing a robust platform for evaluating various combinations of cancer drugs and molecular interactions toward developing effective cancer therapy formulations.

  16. Graphene nanoribbons as a drug delivery agent for lucanthone mediated therapy of glioblastoma multiforme

    SciTech Connect

    Chowdhury, Sayan Mullick; Surhland, Cassandra; Sanchez, Zina; Chaudhary, Pankaj; Suresh Kumar, M. A.; Lee, Stephen; Peña, Louis A.; Waring, Michael; Sitharaman, Balaji; Naidu, Mamta

    2014-08-13

    We report use of PEG-DSPE coated oxidized graphene nanoribbons (O-GNR-PEG-DSPE) as agent for delivery of anti-tumor drug Lucanthone (Luc) into Glioblastoma Multiformae (GBM) cells targeting base excision repair enzyme APE-1 (Apurinic endonuclease-1). Lucanthone, an endonuclease inhibitor of APE-1, was loaded onto O-GNR-PEG-DSPEs using a simple non-covalent method. We found its uptake by GBM cell line U251 exceeding 67% and 60% in APE-1-overexpressing U251, post 24 hours (h). However, their uptake was ~38% and 29% by MCF-7 and rat glial progenitor cells (CG-4), respectively. TEM analysis of U251 showed large aggregates of O-GNR-PEG-DSPE in vesicles. Luc-O-GNR-PEG-DSPE was significantly toxic to U251 but showed little / no toxicity when exposed to MCF-7/CG-4 cells. This differential uptake effect can be exploited to use O-GNR-PEG-DSPEs as a vehicle for Luc delivery to GBM, while reducing nonspecific cytotoxicity to the surrounding healthy tissue. In conclusion, cell death in U251 was necrotic, probably due to oxidative degradation of APE-1.

  17. Graphene Nanoribbons as a Drug Delivery Agent for Lucanthone Mediated Therapy of Glioblastoma Multiforme

    PubMed Central

    Chowdhury, Sayan Mullick; Surhland, Cassandra; Sanchez, Zina; Chaudhary, Pankaj; Kumar, M.A. Suresh; Lee, Stephen; Peña, Louis A.; Waring, Michael; Sitharaman, Balaji; Naidu, Mamta

    2014-01-01

    We report use of PEG-DSPE coated oxidized graphene nanoribbons (O-GNR-PEG-DSPE) as agent for delivery of anti-tumor drug Lucanthone (Luc) into Glioblastoma Multiformae (GBM) cells targeting base excision repair enzyme APE-1 (Apurinic endonuclease-1). Lucanthone, an endonuclease inhibitor of APE-1, was loaded onto O-GNR-PEG-DSPEs using a simple non-covalent method. We found its uptake by GBM cell line U251 exceeding 67% and 60% in APE-1-overexpressing U251, post 24 hours (h). However, their uptake was ~38% and 29% by MCF-7 and rat glial progenitor cells (CG-4), respectively. TEM analysis of U251 showed large aggregates of O-GNR-PEG-DSPE in vesicles. Luc-O-GNR-PEG-DSPE was significantly toxic to U251 but showed little / no toxicity when exposed to MCF-7/CG-4 cells. This differential uptake effect can be exploited to use O-GNR-PEG-DSPEs as a vehicle for Luc delivery to GBM, while reducing nonspecific cytotoxicity to the surrounding healthy tissue. Cell death in U251 was necrotic, probably due to oxidative degradation of APE-1. PMID:25131339

  18. Tumor vascular-targeted co-delivery of anti-angiogenesis and chemotherapeutic agents by mesoporous silica nanoparticle-based drug delivery system for synergetic therapy of tumor

    PubMed Central

    Li, Xiaoyu; Wu, Meiying; Pan, Limin; Shi, Jianlin

    2016-01-01

    To overcome the drawback of drug non-selectivity in traditional chemotherapy, the construction of multifunctional targeting drug delivery systems is one of the most effective and prevailing approaches. The intratumoral anti-angiogenesis and the tumor cell-killing are two basic approaches in fighting tumors. Herein we report a novel tumor vascular-targeting multidrug delivery system using mesoporous silica nanoparticles as carrier to co-load an antiangiogenic agent (combretastatin A4) and a chemotherapeutic drug (doxorubicin) and conjugate with targeting molecules (iRGD peptide) for combined anti-angiogenesis and chemotherapy. Such a dual-loaded drug delivery system is capable of delivering the two agents at tumor vasculature and then within tumors through a differentiated drug release strategy, which consequently results in greatly improved antitumor efficacy at a very low doxorubicin dose of 1.5 mg/kg. The fast release of the antiangiogenic agent at tumor vasculatures led to the disruption of vascular structure and had a synergetic effect with the chemotherapeutic drug slowly released in the following delivery of chemotherapeutic drug into tumors. PMID:26766908

  19. Delivery of optical contrast agents using Triton-X100, part 1: reversible permeabilization of live cells for intracellular labeling

    NASA Astrophysics Data System (ADS)

    van de Ven, Anne L.; Adler-Storthz, Karen; Richards-Kortum, Rebecca

    2009-03-01

    Effective delivery of optical contrast agents into live cells remains a significant challenge. We sought to determine whether Triton-X100, a detergent commonly used for membrane isolation and protein purification, could be used to effectively and reversibly permeabilize live cells for delivery of targeted optical contrast agents. Although Triton-X100 is widely recognized as a good cell permeabilization agent, no systematic study has evaluated the efficiency, reproducibility, and reversibility of Triton-X100-mediated permeabilization in live mammalian cells. We report a series of studies to characterize macromolecule delivery in cells following Triton-X100 treatment. Using this approach, we demonstrate that molecules ranging from 1 to 150 kDa in molecular weight can be reproducibly delivered into live cells by controlling the moles of Triton-X100 relative to the number of cells to be treated. When Triton-X100 is administered at or near the minimum effective concentration, cell permeabilization is generally reversed within 24 h, and treated cells continue to proliferate and show metabolic activity during the restoration of membrane integrity. We conclude that Triton-X100 is a promising permeabilization agent for efficient and reproducible delivery of optical contrast agents into live mammalian cells.

  20. Vitamin B12-mediated transport: a potential tool for tumor targeting of antineoplastic drugs and imaging agents.

    PubMed

    Gupta, Yashwant; Kohli, Dharm Veer; Jain, Sanjay K

    2008-01-01

    The uptake of vitamin B12 (cyanocobalamin, Cbl/VB12) in mammalian cells is mediated by specific, high-affinity receptors for the vitamin B12-binding protein, transcobalamin II, which is expressed on the plasma membrane. The receptor for vitamin B12 is overexpressed on a number of human tumors, including cancers of the ovary, kidney, uterus, testis, brain, colon, lung, and myelocytic blood cells. Furthermore, the affinity of cyanocobalamin conjugates for cell surface transcobalamin II receptors seems to be high enough so that vitamin B12 derivatization with the cytotoxic agent or carriers bearing cytotoxic drugs allows the selective delivery of diagnostic and therapeutic agents to cancer cells. Thus, conjugates of vitamin B12 enter receptor-expressing cancer cells via receptor-mediated endocytosis, and targeting may be accomplished by multiple mechanisms, depending on the drug-delivery strategy. This review summarizes the applications of vitamin B12 as a targeting ligand and highlights the various methods being developed for delivery of therapeutic and imaging agents to cancer cells in vitro and in vivo. This review reflects the potentiality of vitamin B12 for tumor targeting of chemotherapeutic and diagnostic agents.

  1. Evaluation of labdane derivatives as potential anti-inflammatory agents.

    PubMed

    Girón, Natalia; Pérez-Sacau, Elisa; López-Fontal, Raquel; Amaro-Luis, Juan M; Hortelano, Sonsoles; Estevez-Braun, Ana; de Las Heras, Beatriz

    2010-07-01

    In the present study, a series of labdane derivatives (2-9) were prepared from labdanediol (1) and their potential as anti-inflammatory agents were evaluated on lipopolysaccharide (LPS)-treated RAW 264.7 macrophages. All compounds were able to inhibit LPS-induced nitric oxide (NO), although compounds 1, 2, 5, 8 and 9 exhibited the most potent effects with a range of IC(50) values of 5-15 microM. Similarly to the inhibitory effects on NO release, these labdane derivatives also inhibited prostaglandin E(2) (PGE(2)) production. However, analysis of cell viability demonstrated that effects on NO release and (PGE(2)) production of compounds 1, 8 and 9 were due to citotoxicity, whereas compound 2 and 5 did not show any effect in the survival of RAW 264.7 macrophages. In addition to these in vitro data, compound 5 also showed anti-inflammatory activity in vivo, when tested in mice. They prevented the extent of swelling in the TPA-induced ear edema model and inhibited MPO activity, showing similar potency to that of the widely used anti-inflammatory drug indomethacin. These results indicate that compound 2 and in particular compound 5 might be used for the design of new anti-inflammatory agents. Copyright (c) 2010 Elsevier Masson SAS. All rights reserved.

  2. 3-Amidocoumarins as Potential Multifunctional Agents against Neurodegenerative Diseases.

    PubMed

    Matos, Maria João; Rodríguez-Enríquez, Fernanda; Borges, Fernanda; Santana, Lourdes; Uriarte, Eugenio; Estrada, Martín; Rodríguez-Franco, María Isabel; Laguna, Reyes; Viña, Dolores

    2015-12-01

    Monoamine oxidase (MAO) generates reactive oxygen species (ROS), which cause neuronal cell death, causing neurodegeneration. Agents that are able to concurrently inhibit MAO and scavenge free radicals represent promising multifunctional neuroprotective agents that could be used to delay or slow the progression of neurodegenerative diseases. In this work, variously substituted 3-amidocoumarins are described that exert neuroprotection in vitro against hydrogen peroxide in rat cortical neurons, as well as antioxidant activity in a 1,1-diphenyl-2-picrylhydrazyl (DPPH⋅) radical scavenging assay. Selective and reversible inhibitors of the MAO-B isoform were identified. Interestingly, in the case of the 3-benzamidocoumarins, substitution at position 4 with a hydroxy group abolishes MAO-B activity, but the compounds remain active in the neuroprotection model. Further evaluation of 3-heteroarylamide derivatives indicates that it is the nature of the heterocycle that determines the neuroprotective effects. Evaluation in a parallel artificial membrane permeability assay (PAMPA) highlighted the need to further improve the blood-brain barrier permeability of this compound class. However, the compounds described herein adhere to Lipinski's rule of five, suggesting that this novel scaffold has desirable properties for the development of potential drug candidates.

  3. Evolution of contrast agents for ultrasound imaging and ultrasound-mediated drug delivery.

    PubMed

    Paefgen, Vera; Doleschel, Dennis; Kiessling, Fabian

    2015-01-01

    Ultrasound (US) is one of the most frequently used diagnostic methods. It is a non-invasive, comparably inexpensive imaging method with a broad spectrum of applications, which can be increased even more by using bubbles as contrast agents (CAs). There are various different types of bubbles: filled with different gases, composed of soft- or hard-shell materials, and ranging in size from nano- to micrometers. These intravascular CAs enable functional analyses, e.g., to acquire organ perfusion in real-time. Molecular analyses are achieved by coupling specific ligands to the bubbles' shell, which bind to marker molecules in the area of interest. Bubbles can also be loaded with or attached to drugs, peptides or genes and can be destroyed by US pulses to locally release the entrapped agent. Recent studies show that US CAs are also valuable tools in hyperthermia-induced ablation therapy of tumors, or can increase cellular uptake of locally released drugs by enhancing membrane permeability. This review summarizes important steps in the development of US CAs and introduces the current clinical applications of contrast-enhanced US. Additionally, an overview of the recent developments in US probe design for functional and molecular diagnosis as well as for drug delivery is given.

  4. Evolution of contrast agents for ultrasound imaging and ultrasound-mediated drug delivery

    PubMed Central

    Paefgen, Vera; Doleschel, Dennis; Kiessling, Fabian

    2015-01-01

    Ultrasound (US) is one of the most frequently used diagnostic methods. It is a non-invasive, comparably inexpensive imaging method with a broad spectrum of applications, which can be increased even more by using bubbles as contrast agents (CAs). There are various different types of bubbles: filled with different gases, composed of soft- or hard-shell materials, and ranging in size from nano- to micrometers. These intravascular CAs enable functional analyses, e.g., to acquire organ perfusion in real-time. Molecular analyses are achieved by coupling specific ligands to the bubbles’ shell, which bind to marker molecules in the area of interest. Bubbles can also be loaded with or attached to drugs, peptides or genes and can be destroyed by US pulses to locally release the entrapped agent. Recent studies show that US CAs are also valuable tools in hyperthermia-induced ablation therapy of tumors, or can increase cellular uptake of locally released drugs by enhancing membrane permeability. This review summarizes important steps in the development of US CAs and introduces the current clinical applications of contrast-enhanced US. Additionally, an overview of the recent developments in US probe design for functional and molecular diagnosis as well as for drug delivery is given. PMID:26441654

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

    PubMed Central

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

    2012-01-01

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

  6. Therapeutic potential of HMGB1-targeting agents in sepsis

    PubMed Central

    Wang, Haichao; Zhu, Shu; Zhou, Rongrong; Li, Wei; Sama, Andrew E.

    2008-01-01

    Sepsis refers to a systemic inflammatory response syndrome resulting from a microbial infection. The inflammatory response is partly mediated by innate immune cells (such as macrophages, monocytes and neutrophils), which not only ingest and eliminate invading pathogens but also initiate an inflammatory response upon recognition of pathogen-associated molecular patterns (PAMPs). The prevailing theories of sepsis as a dysregulated inflammatory response, as manifested by excessive release of inflammatory mediators such as tumour necrosis factor and high-mobility group box 1 protein (HMGB1), are supported by extensive studies employing animal models of sepsis. Here we review emerging evidence that support extracellular HMGB1 as a late mediator of experimental sepsis, and discuss the therapeutic potential of several HMGB1-targeting agents (including neutralising antibodies and steroid-like tanshinones) in experimental sepsis. PMID:18980707

  7. Potential Anti-HIV Agents from Marine Resources: An Overview

    PubMed Central

    Vo, Thanh-Sang; Kim, Se-Kwon

    2010-01-01

    Human immunodeficiency virus (HIV) infection causes acquired immune deficiency syndrome (AIDS) and is a global public health issue. Anti-HIV therapy involving chemical drugs has improved the life quality of HIV/AIDS patients. However, emergence of HIV drug resistance, side effects and the necessity for long-term anti-HIV treatment are the main reasons for failure of anti-HIV therapy. Therefore, it is essential to isolate novel anti-HIV therapeutics from natural resources. Recently, a great deal of interest has been expressed regarding marine-derived anti-HIV agents such as phlorotannins, sulfated chitooligosaccharides, sulfated polysaccharides, lectins and bioactive peptides. This contribution presents an overview of anti-HIV therapeutics derived from marine resources and their potential application in HIV therapy. PMID:21339954

  8. Aptamer Oligonucleotides: Novel Potential Therapeutic Agents in Autoimmune Disease.

    PubMed

    Li, Weibin; Lan, Xiaopeng

    2015-08-01

    Aptamers are single-stranded deoxyribonucleic acid or ribonucleic acid oligonucleotides generated in vitro based on affinity for certain target molecules by a process known as Systematic Evolution of Ligands by Exponential Enrichment. Aptamers can bind their target molecules with high specificity and selectivity by means of structure compatibility, stacking of aromatic rings, electrostatic and van der Waals interactions, and hydrogen bonding. With several advantages over monoclonal antibodies and other conventional small-molecule therapeutics, such as high specificity and affinity, negligible batch to batch variation, flexible modification and stability, lack of toxicity and low immunogenicity, aptamers are becoming promising novel diagnostic and therapeutic agents. This review focuses on the development of aptamers as potential therapeutics for autoimmune diseases, including diabetes mellitus, multiple sclerosis, rheumatoid arthritis, myasthenia gravis, and systemic lupus erythematosus.

  9. Synthesis, biological evaluation of chrysin derivatives as potential immunosuppressive agents.

    PubMed

    Lv, Peng-Cheng; Cai, Tian-Tian; Qian, Yong; Sun, Juan; Zhu, Hai-Liang

    2011-01-01

    A series of novel chrysin derivatives was firstly synthesized and evaluated on their immunosuppressive activity in the search for potential immunosuppressive agents. Among them, compounds 5c displayed the most potent immunosuppressive inhibitory activity with IC(50) of 0.78 μM, which was comparable to that of cyclosporin A (IC(50) = 0.06 μM). The preliminary mechanism of compound 5c inhibition effects was also detected by flow cytometry (FCM), and the compound exerted immunosuppressive activity via inducing the apoptosis of activated lymph node cells in a dose dependent manner. Furthermore, the estimated LD(50) (in mg/kg) in vivo of compound 5c is 738.2, which indicated that compound 5c was low toxic. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

  10. Ferrous iron-dependent delivery of therapeutic agents to the malaria parasite

    PubMed Central

    Mahajan, Sumit S; Gut, Jiri; Rosenthal, Philip J; Renslo, Adam R

    2013-01-01

    Background The malaria parasites Plasmodium falciparum and Plasmodium vivax generate significant concentrations of free unbound ferrous iron heme as a side product of hemoglobin degradation. The presence of these chemically reactive forms of iron, rare in healthy cells, presents an opportunity for parasite-selective drug delivery. Accordingly, our group is developing technologies for the targeted delivery of therapeutics to the intra-erythrocytic malaria parasite. These so-called ‘fragmenting hybrids’ employ a 1,2,4-trioxolane ring system as an iron(II)-sensing ‘trigger’ moiety and a ‘traceless’ retro-Michael linker to which a variety of partner drug species may be attached. After ferrous iron-promoted activation in the parasite, the partner drug is released via a β-elimination reaction. Methods In this report, we describe three orthogonal experimental approaches that were explored in order to generate in vitro proof-of-concept for ferrous iron-dependent drug delivery from a prototypical fragmenting hybrid. Conclusion Studies of two fragmenting hybrids by orthogonal approaches confirm that a partner drug species can be delivered to live P. falciparum parasites. A key advantage of this approach is the potential to mask a partner drug’s intrinsic bioactivity prior to release in the parasite. PMID:23234548

  11. Protein transduction domain-containing microemulsions as cutaneous delivery systems for an anticancer agent.

    PubMed

    Pepe, Dominique; McCall, Melissa; Zheng, Haian; Lopes, Luciana B

    2013-05-01

    In this study, we developed cationic microemulsions containing a protein transduction domain (penetratin) for optimizing paclitaxel localization within the skin. Microemulsions were prepared by mixing a surfactant blend (BRIJ:ethanol:propylene glycol 2:1:1, w/w/w) with monocaprylin (oil phase) at 1.3:1 ratio, and adding water at 30% (ME-30), 43% (ME-43), and 50% (ME-50). Electrical conductivity and viscosity measurements indicated that ME-30 is most likely a bicontinuous system, whereas ME-43 and ME-50 are water continuous. Their irritation potential, studied in bioengineered skin equivalents, decreased as aqueous content increased. Because ME-50 was not stable in the presence of paclitaxel (0.5%), ME-43 was selected for penetratin incorporation (0.4%). The microemulsion containing penetratin (ME-P) displayed zeta potential of +5.2 mV, and promoted a 1.8-fold increase in paclitaxel cutaneous (but not transdermal) delivery compared with the plain ME-43, whereas the enhancement promoted by another cationic microemulsion containing phytosphingosine was 1.3-fold. Compared with myvacet oil, ME-P promoted a larger increase on transepidermal water loss (twofold) than the plain or the phytosphingosine-containing microemulsions (1.5-fold), suggesting that penetratin addition increases the barrier-disrupting and penetration-enhancing effects of microemulsions. The ratio Δcutaneous/Δtransdermal delivery promoted by ME-P was the highest among the formulations, suggesting its potential for drug localization within cutaneous tumor lesions.

  12. Chitosan-modified PLGA polymeric nanocarriers with better delivery potential for tamoxifen.

    PubMed

    Thakur, Chanchal Kiran; Thotakura, Nagarani; Kumar, Rajendra; Kumar, Pramod; Singh, Bhupinder; Chitkara, Deepak; Raza, Kaisar

    2016-12-01

    Breast cancer is believed as the second most common cause of cancer-related deaths in women for which tamoxifen is frequently prescribed. Despite many promises, tamoxifen is associated with various challenges like low hydrophilicity, poor bioavailability and dose-dependent toxicity. Therefore, it was envisioned to develop tamoxifen- loaded chitosan-PLGA micelles for potential safe and better delivery of this promising agent. The chitosan-PLGA copolymer was synthesised and characterised by Fourier Transform-Infrared, Ultraviolet-visible and Nuclear Magnetic Resonance spectroscopic techniques. The drug-loaded nanocarrier was characterised for drug-pay load, micrometrics, surface charge and morphological attributes. The developed system was evaluated for in-vitro drug release, haemolytic profile, cellular-uptake, anticancer activity by cytotoxicity assay and dermatokinetic studies. The developed nano-system was able to substantially load the drug and control the drug release. The in-vitro cytotoxicity offered by the system was significantly enhanced vis-a-vis plain drug, and there was no substantial haemolysis. The IC50 values were significantly decreased and the nanocarriers were uptaken by MCF-7 cells, noticeably. The carrier was able to locate the drug in the interiors of rat skin in considerable amounts to that of the conventional product. This approach is promising as it provides a biocompatible and effective option for better delivery of tamoxifen. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Cows' milk fat components as potential anticarcinogenic agents.

    PubMed

    Parodi, P W

    1997-06-01

    The optimum approach to conquering cancer is prevention. Although the human diet contains components which promote cancer, it also contains components with the potential to prevent it. Recent research shows that milk fat contains a number of potential anticarcinogenic components including conjugated linoleic acid, sphingomyelin, butyric acid and ether lipids. Conjugated linoleic acid inhibited proliferation of human malignant melanoma, colorectal, breast and lung cancer cell lines. In animals, it reduced the incidence of chemically induced mouse epidermal tumors, mouse forestomach neoplasia and aberrant crypt foci in the rat colon. In a number of studies, conjugated linoleic acid, at near-physiological concentrations, inhibited mammary tumorigenesis independently of the amount and type of fat in the diet. In vitro studies showed that the milk phospholipid, sphingomyelin, through its biologically active metabolites ceramide and sphingosine, participates in three major antiproliferative pathways influencing oncogenesis, namely, inhibition of cell growth, and induction of differentiation and apoptosis. Mice fed sphingomyelin had fewer colon tumors and aberrant crypt foci than control animals. About one third of all milk triacylglycerols contain one molecule of butyric acid, a potent inhibitor of proliferation and inducer of differentiation and apoptosis in a wide range of neoplastic cell lines. Although butyrate produced by colonic fermentation is considered important for colon cancer protection, an animal study suggests dietary butyrate may inhibit mammary tumorigenesis. The dairy cow also has the ability to extract other potential anticarcinogenic agents such as beta-carotene, beta-ionone and gossypol from its feed and transfer them to milk. Animal studies comparing the tumorigenic potential of milk fat or butter with linoleic acid-rich vegetable oils or margarines are reviewed. They clearly show less tumor development with dairy products.

  14. Potential antifertility agents from plants: a comprehensive review.

    PubMed

    Kumar, Dinesh; Kumar, Ajay; Prakash, Om

    2012-03-06

    Traditional medicines are practiced worldwide for regulation fertility since ancient times. This review provides a comprehensive summary of medicinal flora inhabitating throughout the world regarding their traditional usage by various tribes/ethnic groups for fertility regulation in females. Bibliographic investigation was carried out by analyzing classical text books and peer reviewed papers, consulting worldwide accepted scientific databases from the last six decades. Plants/their parts/extracts traditionally used for abortion, contraception, emmenagogue and sterilization purposes have been considered as antifertility agents. Research status of selected potential plant species has been discussed. Further, compounds isolated from plants with attributed fertility regulating potentials are also classified into three categories: (a) phytoconstituents with anti-implantation activity, (b) phytoconstituents with abortifacient activity and (c) phytoconstituents with contraceptive activity. 577 plant species belonging to 122 families, traditionally used in fertility regulation in females, have been recorded, of which 298 plants have been mentioned as abortifacients (42%), 188 as contraceptives (31%), 149 as emmenagogues (24%), and 17 as sterilizers. Among 122 plant families, fabaceae constitutes 49.2%, asteraceae 40.98%, euphorbiaceae 19.7%, apiaceae 16.4%, poaceae 12.3%, labiateae 11.5%, and others in lesser proportion. Various plant parts used in fertility regulation include leaves (25%), roots (22%), fruits (15%), seeds (12%), stem/stem bark (37%), and flowers (4%). Some active compounds, isolated from about various plant species, have been reported to possess significant antifertility potential. This review clearly indicates that it is time to increase the number of experimental studies to find out novel potential chemical entities from such a vast array of unexploited plants having traditional role in fertility regulation. Also, the mechanisms of action by which

  15. Self-assembled potential bio nanocarriers for drug delivery.

    PubMed

    Akter, Nasima; Radiman, Shahidan; Mohamed, Faizal; Reza, Mohammad Imam Hasan

    2013-07-01

    Self-assembled nanocarriers attract increasing attention due to their wide application in various practical fields; among them, one of the most focused fields is drug delivery. Appropriate selection of surfactant is the basis for preparing a successful nanocarrier. Until now, from phospholipid to synthetic surfactants, many surfactants have been used to explore a suitable drug delivery vehicle for the complex in-vivo environment. Among all, bio surfactants are found to be more suitable due to their bio-origin, less-toxicity, biodegradability, cheaper rate and above all, their versatile molecular structures. This molecular property enables them to self assemble into fascinating structures. Moreover, binding DNA, enhancing pH sensitivity and stability allows novelty over their synthetic counterparts and phospholipid. This review paper focuses on the properties and applications of bio-nano-carriers for drug delivery. Micelle, microemulsion, and vesicle are the three nanocarriers which are discussed herein.

  16. Evaluation of Gd-DTPA-monophytanyl and phytantriol nanoassemblies as potential MRI contrast agents.

    PubMed

    Gupta, Abhishek; de Campo, Liliana; Rehmanjan, Beenish; Willis, Scott A; Waddington, Lynne J; Stait-Gardner, Tim; Kirby, Nigel; Price, William S; Moghaddam, Minoo J

    2015-02-03

    Supramolecular self-assembling amphiphiles have been widely used in drug delivery and diagnostic imaging. In this report, we present the self-assembly of Gd (III) chelated DTPA-monophytanyl (Gd-DTPA-MP) amphiphiles incorporated within phytantriol (PT), an inverse bicontinuous cubic phase forming matrix at various compositions. The dispersed colloidal nanoassemblies were evaluated as potential MRI contrast agents at various magnetic field strengths. The homogeneous incorporation of Gd-DTPA-MP in PT was confirmed by polarized optical microscopy (POM) and synchrotron small-angle X-ray scattering (SAXS) of the bulk phases of the mixtures. The liquid crystalline nanostructures, morphology, and the size distribution of the nanoassemblies were studied by SAXS, cryogenic transmission electron microscopy (cryo-TEM), and dynamic light scattering (DLS). The dispersions with up to 2 mol % of Gd-DTPA-MP in PT retained inverse cubosomal nanoassemblies, whereas the rest of the dispersions transformed to liposomal nanoassemblies. In vitro relaxivity studies were performed on all the dispersions at 0.54, 9.40, and 11.74 T and compared to Magnevist, a commercially available contrast agent. All the dispersions showed much higher relaxivities compared to Magnevist at both low and high magnetic field strengths. Image contrast of the nanoassemblies was also found to be much better than Magnevist at the same Gd concentration at 11.74 T. Moreover, the Gd-DTPA-MP/PT dispersions showed improved relaxivities over the pure Gd-DTPA-MP dispersion at high magnetic fields. These stable colloidal nanoassemblies have high potential to be used as combined delivery matrices for diagnostics and therapeutics.

  17. Analysis of a Delivery Device Conversion for Insulin Aspart: Potential Clinical Impact in Veterans

    PubMed Central

    Greck, Beth D.; Killian, Jancy H.

    2016-01-01

    In Brief Insulin therapies using a wide variety of delivery devices are available to accommodate individual patients’ needs. In this study of veterans with diabetes, converting from insulin aspart delivered with vials and syringes to insulin aspart delivered via a pen device resulted in no significant change in A1C. Although insulin pen delivery devices offer benefits, providers should thoroughly consider all potential reasons for uncontrolled diabetes before modifying a patient’s insulin delivery method. PMID:27092019

  18. Potential of Biological Agents in Decontamination of Agricultural Soil

    PubMed Central

    Javaid, Muhammad Kashif; Ashiq, Mehrban; Tahir, Muhammad

    2016-01-01

    Pesticides are widely used for the control of weeds, diseases, and pests of cultivated plants all over the world, mainly since the period after the Second World War. The use of pesticides is very extensive to control harm of pests all over the globe. Persistent nature of most of the synthetic pesticides causes serious environmental concerns. Decontamination of these hazardous chemicals is very essential. This review paper elaborates the potential of various biological agents in decontamination of agricultural soils. The agricultural crop fields are contaminated by the periodic applications of pesticides. Biodegradation is an ecofriendly, cost-effective, highly efficient approach compared to the physical and chemical methods which are expensive as well as unfriendly towards environment. Biodegradation is sensitive to the concentration levels of hydrogen peroxide and nitrogen along with microbial community, temperature, and pH changes. Experimental work for optimum conditions at lab scale can provide very fruitful results about specific bacterial, fungal strains. This study revealed an upper hand of bioremediation over physicochemical approaches. Further studies should be carried out to understand mechanisms of biotransformation. PMID:27293964

  19. Quercetin and rutin as potential agents antifungal against Cryptococcus spp.

    PubMed

    Oliveira, V M; Carraro, E; Auler, M E; Khalil, N M

    2016-01-01

    Amphotericin B is a fungicidal substance that is treatment of choice for most systemic fungal infections affecting as cryptococcosis the immunocompromised patients. However, severe side effects have limited the utility of this drug. The aim of this study was to evaluate the antifungal effect of the combination of amphotericin B with quercetin or rutin and as a protective of citotoxic effect. The antifungal activity to amphotericin B, quercetin and rutin alone and in combination was determined in Candida sp and Cryptococcus neoformans strains. Cytotoxicity test on erythrocytes was performed by spectrophotometric absorbance of hemoglobin. The amphotericin B MIC was reduced when used in combination with quercetin or rutin to C. neoformans ATCC strain and reduced when combined with rutin to a clinical isolate of C. neoformans. In addition, the combination of quercetin with amphotericin B may reduce the toxicity of amphotericin B to red blood cells. Our results suggest that quercetin and rutin are potential agents to combine with amphotericin B in order to reduce the amphotericin dose to lessen side effects and improve antifungal efficacy.

  20. Honey: A Potential Therapeutic Agent for Managing Diabetic Wounds

    PubMed Central

    Islam, Md. Asiful; Gan, Siew Hua; Khalil, Md. Ibrahim

    2014-01-01

    Diabetic wounds are unlike typical wounds in that they are slower to heal, making treatment with conventional topical medications an uphill process. Among several different alternative therapies, honey is an effective choice because it provides comparatively rapid wound healing. Although honey has been used as an alternative medicine for wound healing since ancient times, the application of honey to diabetic wounds has only recently been revived. Because honey has some unique natural features as a wound healer, it works even more effectively on diabetic wounds than on normal wounds. In addition, honey is known as an “all in one” remedy for diabetic wound healing because it can combat many microorganisms that are involved in the wound process and because it possesses antioxidant activity and controls inflammation. In this review, the potential role of honey's antibacterial activity on diabetic wound-related microorganisms and honey's clinical effectiveness in treating diabetic wounds based on the most recent studies is described. Additionally, ways in which honey can be used as a safer, faster, and effective healing agent for diabetic wounds in comparison with other synthetic medications in terms of microbial resistance and treatment costs are also described to support its traditional claims. PMID:25386217

  1. Novel 'soft' beta-blockers as potential safe antiglaucoma agents.

    PubMed

    Bodor, N; elKoussi, A

    1988-04-01

    A series of novel "soft" beta-blockers was designed and synthesized based on the "inactive metabolite approach". Accordingly, the acidic metabolite of metoprolol was converted into various lipophilic esters. The new compounds were tested for their effect on the intraocular pressure (IOP) of rabbits using the ultra-short acting beta-adrenergic antagonist "Esmolol" as a reference compound. Most of the tested compounds displayed a higher and a more prolonged ocular hypotensive activity than the reference methyl ester. The adamantaneethyl ester 2 emerged as the best potential candidate for ophthalmic use as an antiglaucoma agent. This compound exhibited an effective and long lasting ocular hypotensive activity without local irritation to the eye. At the same time, it showed a very fast rate of hydrolysis in human blood (t1/2 = 7.0 minutes) to the inactive acid metabolite. This makes possible effective separation of the desired ocular activity from unwanted systemic beta-blocking action. Unilateral treatment with 2 produced reduction in the IOP only in the treated eye, consistent with the mechanism proposed.

  2. Marine Diterpenoids as Potential Anti-Inflammatory Agents

    PubMed Central

    González, Yisett; Torres-Mendoza, Daniel; Jones, Gillian E.; Fernandez, Patricia L.

    2015-01-01

    The inflammatory response is a highly regulated process, and its dysregulation can lead to the establishment of chronic inflammation and, in some cases, to death. Inflammation is the cause of several diseases, including rheumatoid arthritis, inflammatory bowel diseases, multiple sclerosis, and asthma. The search for agents inhibiting inflammation is a great challenge as the inflammatory response plays an important role in the defense of the host to infections. Marine invertebrates are exceptional sources of new natural products, and among those diterpenoids secondary metabolites exhibit notable anti-inflammatory properties. Novel anti-inflammatory diterpenoids, exclusively produced by marine organisms, have been identified and synthetic molecules based on those structures have been obtained. The anti-inflammatory activity of marine diterpenoids has been attributed to the inhibition of Nuclear Factor-κB activation and to the modulation of arachidonic acid metabolism. However, more research is necessary to describe the mechanisms of action of these secondary metabolites. This review is a compilation of marine diterpenoids, mainly isolated from corals, which have been described as potential anti-inflammatory molecules. PMID:26538822

  3. Fetal Globin Gene Inducers: Novel Agents & New Potential

    PubMed Central

    Perrine, Susan P.; Castaneda, Serguei A.; Chui, David H.; Faller, Douglas V.; Berenson, Ronald J.; Fucharoen, Suthat

    2013-01-01

    Inducing expression of endogenous fetal globin (γ-globin) gene expression to 60-70% of alpha globin synthesis produces β-thalassemia trait globin synthetic ratios and can reduce anemia to a mild level. Several classes of therapeutics have induced γ-globin expression in beta thalassemia patients and subsequently raised total hemoglobin levels, demonstrating proof-of-concept of the approach. Butyrate treatment eliminated transfusion requirements in formerly transfusion-dependent patients with treatment for as long as 7 years. However, prior generations were not readily applicable for widespread use. Currently, a novel oral dual-action therapeutic sodium 2,2-dimethylbutyrate is in clinical trials, an oral decitabine formulation is under development, and agents with complementary mechanisms of action can be applied in combined regimens. Identification of 3 major genetic trait loci which modulate clinical severity provides avenues for developing tailored regimens. These refinements offer renewed potential to apply fetal globin induction as a treatment approach in patient-friendly regimens that can be used world-wide. PMID:20712788

  4. Marine Diterpenoids as Potential Anti-Inflammatory Agents.

    PubMed

    González, Yisett; Torres-Mendoza, Daniel; Jones, Gillian E; Fernandez, Patricia L

    2015-01-01

    The inflammatory response is a highly regulated process, and its dysregulation can lead to the establishment of chronic inflammation and, in some cases, to death. Inflammation is the cause of several diseases, including rheumatoid arthritis, inflammatory bowel diseases, multiple sclerosis, and asthma. The search for agents inhibiting inflammation is a great challenge as the inflammatory response plays an important role in the defense of the host to infections. Marine invertebrates are exceptional sources of new natural products, and among those diterpenoids secondary metabolites exhibit notable anti-inflammatory properties. Novel anti-inflammatory diterpenoids, exclusively produced by marine organisms, have been identified and synthetic molecules based on those structures have been obtained. The anti-inflammatory activity of marine diterpenoids has been attributed to the inhibition of Nuclear Factor-κB activation and to the modulation of arachidonic acid metabolism. However, more research is necessary to describe the mechanisms of action of these secondary metabolites. This review is a compilation of marine diterpenoids, mainly isolated from corals, which have been described as potential anti-inflammatory molecules.

  5. Astaxanthin: A Potential Therapeutic Agent in Cardiovascular Disease

    PubMed Central

    Fassett, Robert G.; Coombes, Jeff S.

    2011-01-01

    Astaxanthin is a xanthophyll carotenoid present in microalgae, fungi, complex plants, seafood, flamingos and quail. It is an antioxidant with anti-inflammatory properties and as such has potential as a therapeutic agent in atherosclerotic cardiovascular disease. Synthetic forms of astaxanthin have been manufactured. The safety, bioavailability and effects of astaxanthin on oxidative stress and inflammation that have relevance to the pathophysiology of atherosclerotic cardiovascular disease, have been assessed in a small number of clinical studies. No adverse events have been reported and there is evidence of a reduction in biomarkers of oxidative stress and inflammation with astaxanthin administration. Experimental studies in several species using an ischaemia-reperfusion myocardial model demonstrated that astaxanthin protects the myocardium when administered both orally or intravenously prior to the induction of the ischaemic event. At this stage we do not know whether astaxanthin is of benefit when administered after a cardiovascular event and no clinical cardiovascular studies in humans have been completed and/or reported. Cardiovascular clinical trials are warranted based on the physicochemical and antioxidant properties, the safety profile and preliminary experimental cardiovascular studies of astaxanthin. PMID:21556169

  6. Astaxanthin: a potential therapeutic agent in cardiovascular disease.

    PubMed

    Fassett, Robert G; Coombes, Jeff S

    2011-03-21

    Astaxanthin is a xanthophyll carotenoid present in microalgae, fungi, complex plants, seafood, flamingos and quail. It is an antioxidant with anti-inflammatory properties and as such has potential as a therapeutic agent in atherosclerotic cardiovascular disease. Synthetic forms of astaxanthin have been manufactured. The safety, bioavailability and effects of astaxanthin on oxidative stress and inflammation that have relevance to the pathophysiology of atherosclerotic cardiovascular disease, have been assessed in a small number of clinical studies. No adverse events have been reported and there is evidence of a reduction in biomarkers of oxidative stress and inflammation with astaxanthin administration. Experimental studies in several species using an ischaemia-reperfusion myocardial model demonstrated that astaxanthin protects the myocardium when administered both orally or intravenously prior to the induction of the ischaemic event. At this stage we do not know whether astaxanthin is of benefit when administered after a cardiovascular event and no clinical cardiovascular studies in humans have been completed and/or reported. Cardiovascular clinical trials are warranted based on the physicochemical and antioxidant properties, the safety profile and preliminary experimental cardiovascular studies of astaxanthin.

  7. Potential of Biological Agents in Decontamination of Agricultural Soil.

    PubMed

    Javaid, Muhammad Kashif; Ashiq, Mehrban; Tahir, Muhammad

    2016-01-01

    Pesticides are widely used for the control of weeds, diseases, and pests of cultivated plants all over the world, mainly since the period after the Second World War. The use of pesticides is very extensive to control harm of pests all over the globe. Persistent nature of most of the synthetic pesticides causes serious environmental concerns. Decontamination of these hazardous chemicals is very essential. This review paper elaborates the potential of various biological agents in decontamination of agricultural soils. The agricultural crop fields are contaminated by the periodic applications of pesticides. Biodegradation is an ecofriendly, cost-effective, highly efficient approach compared to the physical and chemical methods which are expensive as well as unfriendly towards environment. Biodegradation is sensitive to the concentration levels of hydrogen peroxide and nitrogen along with microbial community, temperature, and pH changes. Experimental work for optimum conditions at lab scale can provide very fruitful results about specific bacterial, fungal strains. This study revealed an upper hand of bioremediation over physicochemical approaches. Further studies should be carried out to understand mechanisms of biotransformation.

  8. Animal Venom Peptides: Potential for New Antimicrobial Agents.

    PubMed

    Primon-Barros, Muriel; José Macedo, Alexandre

    2017-01-01

    Microbial infections affect people worldwide, causing diseases with significant impact on public health, indicating the need for research and development of new antimicrobial agents. Animal venoms represent a vast and largely unexploited source of biologically active molecules with attractive candidates for the development of novel therapeutics. Venoms consist of complex mixtures of molecules, including antimicrobial peptides (AMPs). Since the discovery of AMPs, they have been studied as promising new antimicrobial drugs. Amongst the remarkable sources of AMPs with known antimicrobial activities are ants, bees, centipedes, cone snails, scorpions, snakes, spiders, and wasps. The antimicrobial tests against bacteria, protozoans, fungi and viruses using 170 different peptides isolated directly from crude venoms or cDNA libraries of venom glands are listed and discussed in this review, as well as hemolytic ativity. The potential of venoms as source of new compounds, including AMPs, is extensively discussed. Currently, there are six FDA-approved drugs and many others are undergoing preclinical and clinical trials. The search for antimicrobial "weapons" makes the AMPs from venoms promising candidates. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  9. Wasp Venom Toxins as a Potential Therapeutic Agent.

    PubMed

    Dongol, Yashad; Dhananjaya, Bhadrapara L; Shrestha, Rakesh K; Aryal, Gopi

    2016-01-01

    It is high time now to discover novel drugs due to the increasing rate of drug resistance by the pathogen organisms and target cells as well as the dependence or tolerance of the body towards the drug. As it is obvious that significant numbers of the modern day pharmaceuticals are derived from natural products, it is equally astonishing to accept that venoms of various origins have therapeutic potentials. Wasp venoms are also a rich source of therapeutically important toxins which includes short cationic peptides, kinins, polyamines and polyDNA viruses, to name a few indentified. Wasp venom cationic peptides, namely mastoparan and its analogs, show a very important potency as an antimicrobial and anticancer agents of the future. They have proven to be the better candidates due to their lesser toxic effects and higher selectivity upon chemical modification and charge optimization. They also have superiority over the conventional chemical drugs as the target cells very rarely develop resistance against them because these peptides primarily imparts its effect through biophysical interaction with the target cell membrane which is dependent upon the net charge of the peptide, its hydrophobicity and anionicity and fluidity of the target cell membranes. Besides, the other components of wasp venom such as kinins, polyamines and polyDNA viruses show various pharmacological promise in the treatment of pain, inflammatory disease, and neurodegenerative diseases such as epilepsy and aversion.

  10. Nanoparticles as safe and effective delivery systems of antifungal agents: Achievements and challenges.

    PubMed

    Soliman, Ghareb M

    2017-03-19

    Invasive fungal infections are becoming a major health concern in several groups of patients leading to severe morbidity and mortality. Moreover, cutaneous fungal infections are a major cause of visits to outpatient dermatology clinics. Despite the availability of several effective agents in the antifungal drug arena, their therapeutic outcome is less than optimal due to limitations related to drug physicochemical properties and toxicity. For instance, poor aqueous solubility limits the formulation options and efficacy of several azole antifungal drugs while toxicity limits the benefits of many other drugs. Nanoparticles hold great promise to overcome these limitations due to their ability to enhance drug aqueous solubility, bioavailability and antifungal efficacy. Further, drug incorporation into nanoparticles could greatly reduce its toxicity. Despite these interesting nanoparticle features, there are only few marketed nanoparticle-based antifungal drug formulations. This review sheds light on different classes of nanoparticles used in antifungal drug delivery, such as lipid-based vesicles, polymeric micelles, solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsions and dendrimers with emphasis on their advantages and limitations. Translation of these nanoformulations from the lab to the clinic could be facilitated by focusing the research on overcoming problems related to nanoparticle stability, drug loading and high cost of production and standardization.

  11. Progressive development in experimental models of transungual drug delivery of anti-fungal agents.

    PubMed

    Thatai, P; Tiwary, A K; Sapra, B

    2016-02-01

    Pre-clinical development comprises of different procedures that relate drug discovery in the laboratory for commencement of human clinical trials. Pre-clinical studies can be designed to recognize a lead candidate from a list to develop the procedure for scale-up, to choose the unsurpassed formulation, to determine the frequency, and duration of exposure; and eventually make the foundation of the anticipated clinical trial design. The foremost aim in the pharmaceutical research and industry is the claim of drug product quality throughout a drug's life cycle. The particulars of the pre-clinical development process for different candidates may vary; however, all have some common features. Typically in vitro, in vivo or ex vivo studies are elements of pre-clinical studies. Human pharmacokinetic in vivo studies are often supposed to serve as the 'gold standard' to assess product performance. On the other hand, when this general assumption is revisited, it appears that in vitro studies are occasionally better than in vivo studies in assessing dosage forms. The present review is compendious of different such models or approaches that can be used for designing and evaluation of formulations for nail delivery with special reference to anti-fungal agents.

  12. Engineering of bacteria for the visualization of targeted delivery of a cytolytic anticancer agent.

    PubMed

    Jiang, Sheng-Nan; Park, Seung-Hwan; Lee, Hee Jung; Zheng, Jin Hai; Kim, Hyung-Seok; Bom, Hee-Seung; Hong, Yeongjin; Szardenings, Michael; Shin, Myung Geun; Kim, Sun-Chang; Ntziachristos, Vasilis; Choy, Hyon E; Min, Jung-Joon

    2013-11-01

    A number of recent reports have demonstrated that attenuated Salmonella typhimurium are capable of targeting both primary and metastatic tumors. The use of bacteria as a vehicle for the delivery of anticancer drugs requires a mechanism that precisely regulates and visualizes gene expression to ensure the appropriate timing and location of drug production. To integrate these functions into bacteria, we used a repressor-regulated tetracycline efflux system, in which the expression of a therapeutic gene and an imaging reporter gene were controlled by divergent promoters (tetAP and tetRP) in response to extracellular tetracycline. Attenuated S. typhimurium was transformed with the expression plasmids encoding cytolysin A, a therapeutic gene, and renilla luciferase variant 8, an imaging reporter gene, and administered intravenously to tumor-bearing mice. The engineered Salmonella successfully localized to tumor tissue and gene expression was dependent on the concentration of inducer, indicating the feasibility of peripheral control of bacterial gene expression. The bioluminescence signal permitted the localization of gene expression from the bacteria. The engineered bacteria significantly suppressed both primary and metastatic tumors and prolonged survival in mice. Therefore, engineered bacteria that carry a therapeutic and an imaging reporter gene for targeted anticancer therapy can be designed as a theranostic agent.

  13. Use of eptifibatide as a bridge antiplatelet agent for intrathecal drug delivery system placement.

    PubMed

    Sisk, Joseph; Palma, Michael; Cooper, Christopher; Eltahawy, Ehab; Atallah, Joseph

    2012-01-01

    Use of antiplatelet agents is becoming increasingly common, and their management may require new strategies if neuroaxial techniques are to be employed in patients who will not tolerate discontinuation of antiplatelet therapy. The patient was a 46-year-old man with a past medical history significant for coronary artery disease and who had undergone 14 stents. He developed stent thrombosis (ST) while on clopidogrel. Following the ST, he was subsequently placed on prasugrel. While on prasugrel, the patient presented for an intrathecal drug delivery system (IDDS) trial and placement due to severe peripheral neuropathy unresponsive to several conservative medical treatments. He had previously undergone an unsuccessful spinal cord stimulator trial and received no pain relief. In consultation with his outside cardiologist, the patient received permission to hold his prasugrel for 7 days prior to his intrathecal pump trial. During the trial period's inpatient hospitalization, the patient developed chest pain. In consultation with the cardiology service in our institution, it was decided antiplatelet therapy should be re-instituted. The patient was bridged to his IDDS placement after the trial with intravenous eptifibatide. The eptifibatide drip was administered 6 hours prior to the IDDS implant. Functional platelet count was checked one hour before the IDDS was placed and the pump was placed without incident. The eptifibatide drip was reinstituted one hour after the IDDS implantation. The patient was observed for 24 hours on the eptifibatide drip, transitioned to his home dose of prasugrel, and discharged home. At outpatient follow-up one week later, the patient demonstrated no neurologic or hemorrhagic complications and was satisfied with the pain control provided by the IDDS. Prasugrel is an irreversible platelet inhibitor, which prevents ADP-induced platelet aggregation by binding the P2Y12 receptor. Patients taking prasugrel will have deficient platelet activity until

  14. Enhancement of nose-brain delivery of therapeutic agents for treating neurodegenerative diseases using peppermint oil.

    PubMed

    Vaka, S R Kiran; Murthy, S Narasimha

    2010-09-01

    The nose-brain pathway is a potential route for drug delivery as it bypasses the brain barriers. The main objective of this study was to investigate the efficacy of peppermint oil in enhancing the bioavailability of intranasally administered neurotrophins like nerve growth factor (NGF). The effect of different concentrations of peppermint oil (PO) on the delivery of NGF across bovine olfactory epithelium was studied in vitro using Franz diffusion cells. Trans-olfactory epithelial electrical resistance (TEER) was measured to assess the permeability status of the bovine olfactory epithelium. The bioavailability of intranasally administered formulations in rat hippocampus was studied by carrying out brain microdialysis in male Sprague-Dawley rats. Peppermint oil at concentrations of 0.05, 0.1 and 0.5% v/v enhanced the in vitro transport of NGF by 5, 7 and 8 fold, respectively. In vivo studies employing brain microdialysis in rats demonstrated that intranasal administration of NGF formulation with 0.5% PO enhanced the bioavailability by approximately 8 fold compared to rats administered with NGF alone. The bioavailability of NGF in the brain could be enhanced by intranasal administration of peppermint oil.

  15. Potential applications of boron nitride nanotubes as drug delivery systems.

    PubMed

    Ciofani, Gianni

    2010-08-01

    In recent years, there has been an explosion of research in the 'bio-nano' field, with the discovery and introduction of ever more fascinating materials for applications as drug delivery systems, sensors, transducers, and so on. The author's group, for the first time in the literature, proposed boron nitride nanotubes as a valid alternative to carbon nanotubes and other kinds of inorganic materials, because of their improved chemical properties that theoretically guarantee better stability and compatibility in a biological context. In this paper, the bio-applications of boron nitride nanotubes that have emerged in the literature are summarized, with special attention given to their exploitation as safe drug delivery and targeting carriers. Finally, the possibility of combining their physical and chemical properties is approached, highlighting the features that render these innovative nanovectors unique and exceptional candidates for many bio-applications.

  16. Preactivated hyaluronic acid: A potential mucoadhesive polymer for vaginal delivery.

    PubMed

    Nowak, Jessika; Laffleur, Flavia; Bernkop-Schnürch, Andreas

    2015-01-15

    The objective of this study was to develop mucoadhesive polymeric excipients for vaginal drug delivery systems. Hyaluronic acid was thiolated and subsequently preactivated with 6-mercaptonicotinamide (HA-CYS-MNA) to enhance stability and mucoadhesive properties on vaginal mucosa. After determination of the thiol group content, disintegration studies and in vitro mucoadhesion studies (rotating cylinder and tensile) were performed. Furthermore, swelling behavior and cytotoxicity studies were performed in comparison with corresponding polymers. Both, disintegration and in vitro mucoadhesive studies revealed that modifying HA-CYS with MNA resulted in higher stability (3.6-fold prolonged disintegration time compared to unmodified hyaluronic acid) and prolonged mucoadhesion time. MTT assay and LDH revealed no toxicity for the polymeric excipients and safe for their use. Disintegration and swelling results conducted more pronounced stability of the preactivated thiomers compared to corresponding unmodified ones. According to these results preactivated hyaluronic acid might be a useful tool for vaginal delivery systems.

  17. Transdermal Delivery of Drugs with Microneedles—Potential and Challenges

    PubMed Central

    Ita, Kevin

    2015-01-01

    Transdermal drug delivery offers a number of advantages including improved patient compliance, sustained release, avoidance of gastric irritation, as well as elimination of pre-systemic first-pass effect. However, only few medications can be delivered through the transdermal route in therapeutic amounts. Microneedles can be used to enhance transdermal drug delivery. In this review, different types of microneedles are described and their methods of fabrication highlighted. Microneedles can be fabricated in different forms: hollow, solid, and dissolving. There are also hydrogel-forming microneedles. A special attention is paid to hydrogel-forming microneedles. These are innovative microneedles which do not contain drugs but imbibe interstitial fluid to form continuous conduits between dermal microcirculation and an attached patch-type reservoir. Several microneedles approved by regulatory authorities for clinical use are also examined. The last part of this review discusses concerns and challenges regarding microneedle use. PMID:26131647

  18. Development and characterization of site specific target sensitive liposomes for the delivery of thrombolytic agents.

    PubMed

    Vaidya, Bhuvaneshwar; Nayak, Manasa K; Dash, Debabrata; Agrawal, G P; Vyas, Suresh P

    2011-01-17

    In recent times, search for potent and highly selective thrombolytic agents with minimal side effects has become a major area of research. The aim of the present study was to develop and characterize target sensitive (TS) liposomes encapsulating streptokinase, a thrombolytic agent. The developed TS liposomes were composed of dioleylphophatidyl ethanolamine (DOPE) and dipalmityl-c(RGDfK) (10:1mol/mol). Dipalmityl-c(RGDfK) was synthesized using typical carbodiimide chemistry using palmitic acid and c(RGDfK), while lysine was used as a spacer. Liposomes were of 100-120nm size. In vitro drug release study showed that nearly 40% drug of the entrapped drug was released in 12h in the PBS (pH 7.4), however on incubation with activated platelet about 90% of drug was released within 45min. The results suggested target sensitivity of the liposomes. Further, targeting potential was confirmed using fluorescent microscopy and flow cytometry. Clot lysis study revealed that TS liposomes could not only reduce the clot lysis time but also increase the extent of clot lysis as compared to non-liposomal streptokinase solution. In conclusion, the present liposomal formulation will target the thrombolytic agent to the activated platelets in the thrombus and hence will improve the therapeutic efficacy of the drug.

  19. Formulations for Intranasal Delivery of Pharmacological Agents to Combat Brain Disease: A New Opportunity to Tackle GBM?

    PubMed Central

    van Woensel, Matthias; Wauthoz, Nathalie; Rosière, Rémi; Amighi, Karim; Mathieu, Véronique; Lefranc, Florence; van Gool, Stefaan W.; de Vleeschouwer, Steven

    2013-01-01

    Despite recent advances in tumor imaging and chemoradiotherapy, the median overall survival of patients diagnosed with glioblastoma multiforme does not exceed 15 months. Infiltration of glioma cells into the brain parenchyma, and the blood-brain barrier are important hurdles to further increase the efficacy of classic therapeutic tools. Local administration methods of therapeutic agents, such as convection enhanced delivery and intracerebral injections, are often associated with adverse events. The intranasal pathway has been proposed as a non-invasive alternative route to deliver therapeutics to the brain. This route will bypass the blood-brain barrier and limit systemic side effects. Upon presentation at the nasal cavity, pharmacological agents reach the brain via the olfactory and trigeminal nerves. Recently, formulations have been developed to further enhance this nose-to-brain transport, mainly with the use of nanoparticles. In this review, the focus will be on formulations of pharmacological agents, which increase the nasal permeation of hydrophilic agents to the brain, improve delivery at a constant and slow release rate, protect therapeutics from degradation along the pathway, increase mucoadhesion, and facilitate overall nasal transport. A mounting body of evidence is accumulating that the underexplored intranasal delivery route might represent a major breakthrough to combat glioblastoma. PMID:24202332

  20. Potential of CXCR4/CXCL12 Chemokine Axis in Cancer Drug Delivery

    PubMed Central

    Wang, Yan; Xie, Ying; Oupický, David

    2016-01-01

    This review discusses the potential of CXCR4 chemokine receptor in the design of anticancer and antimetastatic drug delivery systems. The role of CXCR4 in cancer progression and metastasis is discussed in the context of the development of several types of drug delivery strategies. Overview of drug delivery systems targeted to cancers that overexpress CXCR4 is provided, together with the main types of CXCR4-binding ligands used in targeting applications. Drug delivery applications that take advantage of CXCR4 inhibition to achieve enhanced anticancer and antimetastatic activity of combination treatments are also discussed. PMID:27088072

  1. N-succinyl chitosan as buccal penetration enhancer for delivery of herbal agents in treatment of oral mucositis.

    PubMed

    Dhawan, Neha; Kumar, Krishan; Kalia, A N; Arora, Saahil

    2014-01-01

    Oral mucositis is one of the major side effects of cancer chemotherapy (30-76%) and radiotherapy (over 50%). Current palliative treatments of oral mucositis include specialized agents like pelifermin, platelet derived factors etc. or oral hygienic agents which suffered from various drawbacks like systemic side effect, least effect owing to fast wash out of buccal mucosa, patient unfriendly delivery systems, and mere symptomatic relief. In this research work, N-succinyl chitosan gel delivery system of microemulsified eugenol, honey and sodium hyaluronate was prepared to explore their multiple and synergistic effects on various pathological factors of oral mucositis. N-succinyl chitosan was synthesized in our laboratory and loaded with microemulsified eugenol (10% v/v), honey (10% v/v) and sodium hyaluronate (0.2% w/v) to prepare orogel with optimum pH, spreadability, mucoadhesion strength, and viscosity. In vitro eugenol release from N-succinyl chitosan gel after 8 hours in PBS (pH-6.4) was found to be 87.45±0.14%, which was better in comparison to that released from chitosan gel. Ex vivo penetration studies using rat buccal mucosal tissue also suggested better J-efflux of eugenol through N-succinyl chitosan in comparison to chitosan gel with enhancement ratio (ER) of 1.71. The antimicrobial effect of N-succinyl chitosan based orogel against S. aureus and C. albicans efficacy was found to be statistically high in comparison to chitosan based orogel as well as marketed formulation of chlorhexidine (p<0.05). The N-succinyl chitosan orogel in 5-fluoro uracil induced oral mucositis animal (Wistar rats) model showed enhanced survival ratio, weight gain and high tissue regeneration activity than chitosan gel formulation within 15 days. The formulation was successful in elevating the survival and reducing the inflammation in the oral mucosa of animals compared to disease control (p<0.05) and hence suggesting the potential of N-succinyl chitosan orogel in the treatment of

  2. Disulfiram attenuates osteoclast differentiation in vitro: a potential antiresorptive agent.

    PubMed

    Ying, Hua; Qin, An; Cheng, Tak S; Pavlos, Nathan J; Rea, Sarah; Dai, Kerong; Zheng, Ming H

    2015-01-01

    Disulfiram (DSF), a cysteine modifying compound, has long been clinically employed for the treatment of alcohol addiction. Mechanistically, DSF acts as a modulator of MAPK and NF-κB pathways signaling pathways. While these pathways are crucial for osteoclast (OC) differentiation, the potential influence of DSF on OC formation and function has not been directly assessed. Here, we explore the pharmacological effects of DSF on OC differentiation, activity and the modulation of osteoclastogenic signaling cascades. We first analyzed cytotoxicity of DSF on bone marrow monocytes isolated from C57BL/6J mice. Upon the establishment of optimal dosage, we conducted osteoclastogenesis and bone resorption assays in the presence or absence of DSF treatment. Luciferase assays in RAW264.7 cells were used to examine the effects of DSF on major transcription factors activation. Western blot, reverse transcription polymerase chain reaction, intracellular acidification and proton influx assays were employed to further dissect the underlying mechanism. DSF treatment dose-dependently inhibited both mouse and human osteoclastogenesis, especially at early stages of differentiation. This inhibition correlated with a decrease in the expression of key osteoclastic marker genes including CtsK, TRAP, DC-STAMP and Atp6v0d2 as well as a reduction in bone resorption in vitro. Suppression of OC differentiation was found to be due, at least in part, to the blockade of several key receptor activators of nuclear factor kappa-B ligand (RANKL)-signaling pathways including ERK, NF-κB and NFATc1. On the other hand, DSF failed to suppress intracellular acidification and proton influx in mouse and human osteoclasts using acridine orange quenching and microsome-based proton transport assays. Our findings indicate that DSF attenuates OC differentiation via the collective suppression of several key RANKL-mediated signaling cascades, thus making it an attractive agent for the treatment of OC

  3. Disulfiram Attenuates Osteoclast Differentiation In Vitro: A Potential Antiresorptive Agent

    PubMed Central

    Cheng, Tak S.; Pavlos, Nathan J.; Rea, Sarah; Dai, Kerong; Zheng, Ming H.

    2015-01-01

    Disulfiram (DSF), a cysteine modifying compound, has long been clinically employed for the treatment of alcohol addiction. Mechanistically, DSF acts as a modulator of MAPK and NF-κB pathways signaling pathways. While these pathways are crucial for osteoclast (OC) differentiation, the potential influence of DSF on OC formation and function has not been directly assessed. Here, we explore the pharmacological effects of DSF on OC differentiation, activity and the modulation of osteoclastogenic signaling cascades. We first analyzed cytotoxicity of DSF on bone marrow monocytes isolated from C57BL/6J mice. Upon the establishment of optimal dosage, we conducted osteoclastogenesis and bone resorption assays in the presence or absence of DSF treatment. Luciferase assays in RAW264.7 cells were used to examine the effects of DSF on major transcription factors activation. Western blot, reverse transcription polymerase chain reaction, intracellular acidification and proton influx assays were employed to further dissect the underlying mechanism. DSF treatment dose-dependently inhibited both mouse and human osteoclastogenesis, especially at early stages of differentiation. This inhibition correlated with a decrease in the expression of key osteoclastic marker genes including CtsK, TRAP, DC-STAMP and Atp6v0d2 as well as a reduction in bone resorption in vitro. Suppression of OC differentiation was found to be due, at least in part, to the blockade of several key receptor activators of nuclear factor kappa-B ligand (RANKL)-signaling pathways including ERK, NF-κB and NFATc1. On the other hand, DSF failed to suppress intracellular acidification and proton influx in mouse and human osteoclasts using acridine orange quenching and microsome-based proton transport assays. Our findings indicate that DSF attenuates OC differentiation via the collective suppression of several key RANKL-mediated signaling cascades, thus making it an attractive agent for the treatment of OC

  4. Microbubbles as drug-delivery vectors: steering ultrasound contrast agents in arterial flow using the Bjerknes force

    NASA Astrophysics Data System (ADS)

    Aliseda, Alberto; Clark, Alicia

    2012-11-01

    Micron-sized coated microbubbles, commonly referred to as ultrasound contrast agents (UCAs), have been identified as potential targeted drug delivery vectors with applications in cancer chemotherapy and thrombolysis. The Bjerknes force, produced by the fluctuating pressure field created by the ultrasound waves acting on the oscillating bubble with a phase lag induced by the liquid's inertia and viscosity, can be used to direct the microbubbles to specific targeted areas in the circulatory system. While this phenomenon is well understood in a quiescent fluid, we need a better understanding of the dynamics of microbubbles in the complex pulsatile flow found in the human circulatory system. The non-linear interactions of ultrasound volume oscillations and flow-induced stresses are explored via high speed imaging of UCAs under in vitro flow that reproduces conditions in large arteries (relatively high Reynolds and Womersley numbers). This improved understanding will be used to manipulate and steer UCAs with ultrasound, in conjunction with hydrodynamic forces. NSF CAREER, NSF Graduate Research Fellowship.

  5. The Smart Drug Delivery System and Its Clinical Potential

    PubMed Central

    Liu, Dong; Yang, Fang; Xiong, Fei; Gu, Ning

    2016-01-01

    With the unprecedented progresses of biomedical nanotechnology during the past few decades, conventional drug delivery systems (DDSs) have been involved into smart DDSs with stimuli-responsive characteristics. Benefiting from the response to specific internal or external triggers, those well-defined nanoplatforms can increase the drug targeting efficacy, in the meantime, reduce side effects/toxicities of payloads, which are key factors for improving patient compliance. In academic field, variety of smart DDSs have been abundantly demonstrated for various intriguing systems, such as stimuli-responsive polymeric nanoparticles, liposomes, metals/metal oxides, and exosomes. However, these nanoplatforms are lack of standardized manufacturing method, toxicity assessment experience, and clear relevance between the pre-clinical and clinical studies, resulting in the huge difficulties to obtain regulatory and ethics approval. Therefore, such relatively complex stimulus-sensitive nano-DDSs are not currently approved for clinical use. In this review, we highlight the recent advances of smart nanoplatforms for targeting drug delivery. Furthermore, the clinical translation obstacles faced by these smart nanoplatforms have been reviewed and discussed. We also present the future directions and perspectives of stimuli-sensitive DDS in clinical applications. PMID:27375781

  6. The Smart Drug Delivery System and Its Clinical Potential.

    PubMed

    Liu, Dong; Yang, Fang; Xiong, Fei; Gu, Ning

    2016-01-01

    With the unprecedented progresses of biomedical nanotechnology during the past few decades, conventional drug delivery systems (DDSs) have been involved into smart DDSs with stimuli-responsive characteristics. Benefiting from the response to specific internal or external triggers, those well-defined nanoplatforms can increase the drug targeting efficacy, in the meantime, reduce side effects/toxicities of payloads, which are key factors for improving patient compliance. In academic field, variety of smart DDSs have been abundantly demonstrated for various intriguing systems, such as stimuli-responsive polymeric nanoparticles, liposomes, metals/metal oxides, and exosomes. However, these nanoplatforms are lack of standardized manufacturing method, toxicity assessment experience, and clear relevance between the pre-clinical and clinical studies, resulting in the huge difficulties to obtain regulatory and ethics approval. Therefore, such relatively complex stimulus-sensitive nano-DDSs are not currently approved for clinical use. In this review, we highlight the recent advances of smart nanoplatforms for targeting drug delivery. Furthermore, the clinical translation obstacles faced by these smart nanoplatforms have been reviewed and discussed. We also present the future directions and perspectives of stimuli-sensitive DDS in clinical applications.

  7. In vitro delivery of anti-breast cancer agents directly via the mammary papilla (nipple).

    PubMed

    Lee, Lay Ming; Davison, Zoë; Heard, Charles M

    2010-03-15

    The objective of this study was to investigate, in vitro, the plausibility of a novel method for delivering a combination of anti-breast cancer agents to the breast via the mammary papilla (nipple). Mammary papillae were prepared from freshly excised strips of porcine sow breasts by blunt dissection. Permeation studies were performed using all glass Franz diffusion cells in both upright and lateral position, with drugs examined individually and in combination. Donor phase was comprised of equimolar PD98059, LY294002 and tamoxifen; 2.54x10(-4) mol dissolved in 950 microL fish oil (containing approximately 23% (w/v) eicosapentaenoic acid, EPA), 25 microL DMSO and 25 microL 1,8-cineole. Also, 4 or 10% Cabosil M5P (w/v) was added to thicken the formulation. After 6 h, the papillae were recovered, cleaned, centrifuged and extracted thrice with methanol. Pooled extracts were analysed by reversed-phase HPLC. The significance of the papilla orientation was also investigated. When applied singly and laterally, the amount extracted from the porcine breast tissue for PD98059, LY294002 and tamoxifen were 1.83+/-0.30, 10.67+/-1.78 and 0.74+/-0.19x10(-2) micromol g(-1) respectively; applied simultaneously and laterally, 2.03+/-0.14, 4.86+/-0.47 and 0.22+/-0.04x10(-2) micromol g(-1) respectively. With 4% Cabosil formulation, amount extracted for PD98059 and LY294002 were 5.71+/-0.95 and 9.91+/-0.92x10(-2) micromol g(-1) respectively; with 10% formulation, 2.64+/-0.5 and 3.90+/-0.78x10(-2) micromol g(-1) respectively. Tamoxifen was below its limit of detection in both Cabosil M5P formulations. To conclude, localized passive delivery via the mammary papilla is a plausible non-invasive means of delivering anti-breast cancer drugs directly to the breast, in levels that have previously been shown to markedly inhibit the growth of breast cancer cell lines, in vitro. The amounts deliverable may be influenced by differential interactions with the thickening agent and patient orientation.

  8. Buoyancy-generating agents for stomach-specific drug delivery: an overview with special emphasis on floating behavior.

    PubMed

    Ishak, Rania A H

    2015-01-01

    Gastric retentive drug delivery provides a promising technology exhibiting an extended gastric residence and a drug release independent of patient related variables. It is usually useful in improving local gastric treatment as well as overcoming drug-related problems .i.e. drugs having narrow absorption window, short half-life or low intestinal solubility. Buoyancy is considered one of the most promising approaches for gastro-retention of dosage forms. Floating drug delivery systems have a bulk density lower than gastric fluids and thus remain buoyant in the stomach causing an increase in gastric residence time. The buoyancy of these systems is attained by the aid of substances responsible to generate the low density. Various agents with different mechanisms were adopted either gas-generating agents, air entrapping swellable polymers, inherent low density substances, porous excipients, hollow/porous particles inducing preparation techniques or sublimating agents. Therefore, this review gives an exclusive descriptive classification of the different categories of these buoyancy-generating agents while representing the related research works. An overview is also conducted to describe relevant techniques assessing the floating behavior of such dosage forms either in vitro or in vivo. Finally, a collection representing FDA-approved floating pharmaceutical products is adopted with emphasis on the buoyancy-generating agent type used in each product.

  9. Enzyme-triggered, cell penetrating peptide-mediated delivery of anti-tumor agents.

    PubMed

    He, Huining; Sun, Lu; Ye, Junxiao; Liu, Ergang; Chen, Sunhui; Liang, Qiuling; Shin, Meong Cheol; Yang, Victor C

    2016-10-28

    Conventional chemotherapy has little or no specificity for cancer cells, normally resulting in low drug accumulation at the tumor region (inefficacy) and drug-induced severe side effects (toxicity). Nowadays, new strategies have been developed to improve both the targeting ability and cellular drug uptake using active targeting ligands and drug internalization agents, which could recognize and interact with specific receptors overexpressed on tumor cells and then trigger a drug internalization process by transporting the cargos into cells. Among those strategies, enzyme-triggered cell penetrating peptide (CPP)-mediated systems seem to be a feasible approach. The expression level of specific enzymes like proteases, esterases or glycosidases is often higher in tumor cells than in normal tissues, and such concentration gradients can be exploited as a tool for targeted cancer therapy. CPPs are known to be effective in promoting membrane transportation of the drug cargos, rendering a deeper tumor permeation that could further enhance the therapeutic efficacy of the delivered drug. An enzyme-triggered, CPP-mediated system would combine these advantages to yield a system with the enhanced tumor targeting ability and internalization efficiency and so far many systems have been successfully exploited and applied to cancer therapy. In this review, typical enzymes applied in cancer theranostic systems were firstly reviewed, followed by analyzing pros and cons of cell penetrating peptides. Most importantly, different types of applications of enzyme-triggered CPP-mediated systems in tumor imaging were illustrated. Finally, the drug loaded applications, i.e. enzyme-triggered CPP-mediated systems in drug delivery were reviewed. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Eudraginated polymer blends: a potential oral controlled drug delivery system for theophylline.

    PubMed

    Emeje, Martins; John-Africa, Lucy; Isimi, Yetunde; Kunle, Olobayo; Ofoefule, Sabinus

    2012-03-01

    Sustained release (SR) dosage forms enable prolonged and continuous deposition of the drug in the gastrointestinal (GI) tract and improve the bioavailability of medications characterized by a narrow absorption window. In this study, a new strategy is proposed for the development of SR dosage forms for theophylline (TPH). Design of the delivery system was based on a sustained release formulation, with a modified coating technique and swelling features aimed to extend the release time of the drug. Different polymers, such as Carbopol 71G (CP), sodium carboxymethylcellulose (SCMC), ethylcellulose (EC) and their combinations were tried. Prepared matrix tablets were coated with a 5 % (m/m) dispersion of Eudragit (EUD) in order to get the desired sustained release profile over a period of 24 h. Various formulations were evaluated for micromeritic properties, drug concentration and in vitro drug release. It was found that the in vitro drug release rate decreased with increasing the amount of polymer. Coating with EUD resulted in a significant lag phase in the first two hours of dissolution in the acidic pH of simulated gastric fluid (SGF) due to decreased water uptake, and hence decreased driving force for drug release. Release became faster in the alkaline pH of simulated intestinal fluid (SIF) owing to increased solubility of both the coating and matrixing agents. The optimized formulation was subjected to in vivo studies in rabbits and the pharmacokinetic parameters of developed formulations were compared with the commercial (Asmanyl(®)) formulation. Asmanyl(®) tablets showed faster absorption (t(max) 4.0 h) compared to the TPH formulation showing a t(max) value of 8.0 h. The C(max) and AUC values of TPH formulation were significantly (p < 0.05) higher than those for Asmanyl(®), revealing relative bioavailability of about 136.93 %. Our study demonstrated the potential usefulness of eudraginated polymers for the oral delivery of the sparingly soluble drug

  11. Impact of Absorption and Transport on Intelligent Therapeutics and Nano-scale Delivery of Protein Therapeutic Agents

    PubMed Central

    Peppas, Nicholas A.; Carr, Daniel A

    2009-01-01

    The combination of materials design and advances in nanotechnology has led to the development of new therapeutic protein delivery systems. The pulmonary, nasal, buccal and other routes have been investigated as delivery options for protein therapy, but none result in improved patient compliances and patient quality of life as the oral route. For the oral administration of these new systems, an understanding of protein transport is essential because of the dynamic nature of the gastrointestinal tract and the barriers to transport that exist. Models have been developed to describe the transport between the gastrointestinal lumen and the bloodstream, and laboratory techniques like cell culture provide a means to investigate the absorption and transport of many therapeutic agents. Biomaterials, including stimuli-sensitive complexation hydrogels, have been investigated as promising carriers for oral delivery. However, the need to develop models that accurately predict protein blood concentration as a function of the material structure and properties still exists. PMID:20161384

  12. Francisella tularensis as a potential agent of bioterrorism?

    PubMed

    Maurin, Max

    2015-02-01

    Francisella tularensis is a category A bioterrorism agent. It is the etiological agent of tularemia, a zoonotic disease found throughout the northern hemisphere. The intentional spread of F. tularensis aerosols would probably lead to severe and often fatal pneumonia cases, but also secondary cases from contaminated animals and environments. We are not ready to face such a situation. No vaccine is currently available. A few antibiotics are active against F. tularensis, but strains resistant to these antibiotics could be used in the context of bioterrorism. We need new therapeutic strategies to fight against category A bioterrorism agents, including development of new drugs inhibiting F. tularensis growth and/or virulence, or enhancing the host response to infection by this pathogen.

  13. Fibrin nanoconstructs: a novel processing method and their use as controlled delivery agents

    NASA Astrophysics Data System (ADS)

    Praveen, G.; Sreerekha, P. R.; Menon, Deepthy; Nair, Shantikumar V.; Prasad Chennazhi, Krishna

    2012-03-01

    Fibrin nanoconstructs (FNCs) were prepared through a modified water-in-oil emulsification-diffusion route without the use of any surfactants, resulting in a high yield synthesis of fibrin nanotubes (FNTs) and fibrin nanoparticles (FNPs). The fibrin nanoconstructs formed an aligned structure with self-assembled nanotubes with closed heads that eventually formed spherical nanoparticles of size ˜250 nm. The nanotubes were typically ˜700 nm long and 150-300 nm in diameter, with a wall thickness of ˜50 nm and pore diameter of about 150-250 nm. These constructs showed high stability against aggregation indicated by a zeta potential of -44 mV and an excellent temperature stability upto 200 °C. Furthermore, they were found to be enzymatically degradable, thereby precluding any long term toxicity effects. These unique fibrin nanostructures were analyzed for their ability to deliver tacrolimus, an immunosuppressive drug that is used widely to prevent the initial phase of tissue rejection during allogenic transplantation surgeries. Upon conjugation with tacrolimus, a drug encapsulation efficiency of 66% was achieved, with the in vitro release studies in PBS depicting a sustained and complete drug release over a period of one week at the physiological pH of 7.4. At a more acidic pH, the drug release was very slow, suggesting their potential for oral-intestinal drug administration as well. The in vivo drug absorption rates analyzed in Sprague Dawley rats further confirmed the sustained release pattern of tacrolimus for both oral and parenteral delivery routes. The novel fibrin nanoconstructs developed using a green chemistry approach thus proved to be excellent biodegradable nanocarriers for oral as well as parenteral administrations, with remarkable potential also for delivering specific growth factors in tissue engineering scaffolds.

  14. New old challenges in tuberculosis: potentially effective nanotechnologies in drug delivery.

    PubMed

    Sosnik, Alejandro; Carcaboso, Angel M; Glisoni, Romina J; Moretton, Marcela A; Chiappetta, Diego A

    2010-03-18

    Tuberculosis (TB) is the second most deadly infectious disease. Despite potentially curative pharmacotherapies being available for over 50 years, the length of the treatment and the pill burden can hamper patient lifestyle. Thus, low compliance and adherence to administration schedules remain the main reasons for therapeutic failure and contribute to the development of multi-drug-resistant (MDR) strains. Pediatric patients constitute a high risk population. Most of the first-line drugs are not commercially available in pediatric form. The design of novel antibiotics attempts to overcome drug resistance, to shorten the treatment course and to reduce drug interactions with antiretroviral therapies. On the other hand, the existing anti-TB drugs are still effective. Overcoming technological drawbacks of these therapeutic agents as well as improving the effectiveness of the drug by targeting the infection reservoirs remains the central aims of Pharmaceutical Technology. In this framework, nanotechnologies appear as one of the most promising approaches for the development of more effective and compliant medicines. The present review thoroughly overviews the state-of-the-art in the development of nano-based drug delivery systems for encapsulation and release of anti-TB drugs and discusses the challenges that are faced in the development of a more effective, compliant and also affordable TB pharmacotherapy.

  15. High-throughput assay for optimising microbial biological control agent production and delivery

    USDA-ARS?s Scientific Manuscript database

    Lack of technologies to produce and deliver effective biological control agents (BCAs) is a major barrier to their commercialization. A myriad of variables associated with BCA cultivation, formulation, drying, storage, and reconstitution processes complicates agent quality maximization. An efficie...

  16. Mechanical and dynamic characteristics of encapsulated microbubbles coupled by magnetic nanoparticles as multifunctional imaging and drug delivery agents.

    PubMed

    Guo, Gepu; Lu, Lu; Yin, Leilei; Tu, Juan; Guo, Xiasheng; Wu, Junru; Xu, Di; Zhang, Dong

    2014-11-21

    Development of magnetic encapsulated microbubble agents that can integrate multiple diagnostic and therapeutic functions is a key focus in both biomedical engineering and nanotechnology and one which will have far-reaching impact on medical diagnosis and therapies. However, properly designing multifunctional agents that can satisfy particular diagnostic/therapeutic requirements has been recognized as rather challenging, because there is a lack of comprehensive understanding of how the integration of magnetic nanoparticles to microbubble encapsulating shells affects their mechanical properties and dynamic performance in ultrasound imaging and drug delivery. Here, a multifunctional imaging contrast and in-situ gene/drug delivery agent was synthesized by coupling super paramagnetic iron oxide nanoparticles (SPIOs) into albumin-shelled microbubbles. Systematical studies were performed to investigate the SPIO-concentration-dependence of microbubble mechanical properties, acoustic scattering response, inertial cavitation activity and ultrasound-facilitated gene transfection effect. These demonstrated that, with the increasing SPIO concentration, the microbubble mean diameter and shell stiffness increased and ultrasound scattering response and inertial cavitation activity could be significantly enhanced. However, an optimized ultrasound-facilitated vascular endothelial growth factor transfection outcome would be achieved by adopting magnetic albumin-shelled microbubbles with an appropriate SPIO concentration of 114.7 µg ml(-1). The current results would provide helpful guidance for future development of multifunctional agents and further optimization of their diagnostic/therapeutic performance in clinic.

  17. Mechanical and dynamic characteristics of encapsulated microbubbles coupled by magnetic nanoparticles as multifunctional imaging and drug delivery agents

    NASA Astrophysics Data System (ADS)

    Guo, Gepu; Lu, Lu; Yin, Leilei; Tu, Juan; Guo, Xiasheng; Wu, Junru; Xu, Di; Zhang, Dong

    2014-11-01

    Development of magnetic encapsulated microbubble agents that can integrate multiple diagnostic and therapeutic functions is a key focus in both biomedical engineering and nanotechnology and one which will have far-reaching impact on medical diagnosis and therapies. However, properly designing multifunctional agents that can satisfy particular diagnostic/therapeutic requirements has been recognized as rather challenging, because there is a lack of comprehensive understanding of how the integration of magnetic nanoparticles to microbubble encapsulating shells affects their mechanical properties and dynamic performance in ultrasound imaging and drug delivery. Here, a multifunctional imaging contrast and in-situ gene/drug delivery agent was synthesized by coupling super paramagnetic iron oxide nanoparticles (SPIOs) into albumin-shelled microbubbles. Systematical studies were performed to investigate the SPIO-concentration-dependence of microbubble mechanical properties, acoustic scattering response, inertial cavitation activity and ultrasound-facilitated gene transfection effect. These demonstrated that, with the increasing SPIO concentration, the microbubble mean diameter and shell stiffness increased and ultrasound scattering response and inertial cavitation activity could be significantly enhanced. However, an optimized ultrasound-facilitated vascular endothelial growth factor transfection outcome would be achieved by adopting magnetic albumin-shelled microbubbles with an appropriate SPIO concentration of 114.7 µg ml-1. The current results would provide helpful guidance for future development of multifunctional agents and further optimization of their diagnostic/therapeutic performance in clinic.

  18. Liposomes as a potential ocular delivery system of distamycin A.

    PubMed

    Chetoni, Patrizia; Monti, Daniela; Tampucci, Silvia; Matteoli, Barbara; Ceccherini-Nelli, Luca; Subissi, Alessando; Burgalassi, Susi

    2015-08-15

    Liposomes containing Distamycin A (DA) may be clinically useful in the treatment of ocular HSV infections, especially in acyclovir-resistant HSV keratitis. This study evaluated the in vitro and in vivo performance of a topical controlled release liposomal formulation containing DA (DA-Lipo) aimed at reducing the toxicity of the encapsulated active agent and improving drug uptake by ocular tissues. The bioavailability of DA in the tear fluid and the DA uptake into the cornea were increased after instillation of DA-Lipo in rabbits, reaching the DA corneal concentration corresponding to IC50 values against HSV without any sign of transcorneal permeation of drug. DA-Lipo was definitely less cytotoxic then plain DA in rabbit corneal epithelial cells. These results provide new insights into the correlation between the in vitro data and the drug kinetics following ocular applications of liposomal vesicles. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Protein delivery into live cells by incubation with an endosomolytic agent

    PubMed Central

    Erazo-Oliveras, Alfredo; Najjar, Kristina; Dayani, Laila; Wang, Ting-Yi; Johnson, Gregory A.; Pellois, Jean-Philippe

    2014-01-01

    We report on how a dimer of the cell-penetrating peptide TAT, dfTAT, penetrates live cells by escaping from endosomes with a particularly high efficiency. By mediating endosomal leakage, dfTAT also delivers proteins into cultured cells after a simple co-incubation procedure. Cytosolic delivery is achieved in most cells in a culture and only a relatively small amount of material remains trapped inside endosomes. Delivery does not require binding interactions between dfTAT and a protein, multiple molecules can be delivered at once, and delivery can be repeated. Remarkably, dfTAT-mediated delivery does not noticeably impact cell viability, proliferation, or gene expression. This new delivery strategy should be extremely useful for cell-based assays, cellular imaging applications, and the ex vivo manipulation of cells. PMID:24930129

  20. Synthesis, characterization, and cytocompatibility of potential cockle shell aragonite nanocrystals for osteoporosis therapy and hormonal delivery

    PubMed Central

    Jaji, Alhaji Zubair; Bakar, Md Zuki Bin Abu; Mahmud, Rozi; Loqman, Mohamad Yusof; Hezmee, Mohamad Noor Mohamad; Isa, Tijani; Wenliang, Fu; Hammadi, Nahidah Ibrahim

    2017-01-01

    Calcium carbonate is a porous inorganic nanomaterial with huge potential in biomedical applications and controlled drug delivery. This study aimed at evaluating the physicochemical properties and in vitro efficacy and safety of cockle shell aragonite calcium carbonate nanocrystals (ANC) as a potential therapeutic and hormonal delivery vehicle for osteoporosis management. Free and human recombinant parathyroid hormone 1-34 (PTH 1-34)-loaded cockle shell aragonite calcium carbonate nanocrystals (PTH-ANC) were synthesized and evaluated using standard procedures. Transmission electron microscopy and field emission scanning electron microscopy results demonstrated highly homogenized spherical-shaped aragonite nanocrystals of 30±5 nm diameter. PTH-ANC had a zeta potential of −27.6±8.9 mV. The encapsulation efficiency of the formulation was found to be directly proportional to the concentrations of the drug fed. The X-ray diffraction patterns revealed strong crystallizations with no positional change of peaks before and after PTH-ANC synthesis. Fourier transform infrared spectroscopy demonstrated no detectable interactions between micron-sized aragonite and surfactant at molecular level. PTH-ANC formulation was stabilized at pH 7.5, enabling sustained slow release of PTH 1-34 for 168 h (1 week). A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cytocompatibility assay in Human Foetal Osteoblast Cell Line hFOB 1.19 showed that ANC can safely support osteoblast proliferation up to 48 h whereas PTH-ANC can safely support the proliferation at 72 h and beyond due to the sustained slow release of PTH 1-34. It was concluded that due to its biogenic nature, ANC is a cytocompatible antiosteoporotic agent. It doubles as a nanocarrier for the enhancement of efficacy and safety of the bone anabolic PTH 1-34. ANC is expected to reduce the cost, dosage, and dose frequency associated with the use of PTH 1-34 management of primary and secondary forms of osteoporosis

  1. Synthesis, characterization, and cytocompatibility of potential cockle shell aragonite nanocrystals for osteoporosis therapy and hormonal delivery.

    PubMed

    Jaji, Alhaji Zubair; Bakar, Md Zuki Bin Abu; Mahmud, Rozi; Loqman, Mohamad Yusof; Hezmee, Mohamad Noor Mohamad; Isa, Tijani; Wenliang, Fu; Hammadi, Nahidah Ibrahim

    2017-01-01

    Calcium carbonate is a porous inorganic nanomaterial with huge potential in biomedical applications and controlled drug delivery. This study aimed at evaluating the physicochemical properties and in vitro efficacy and safety of cockle shell aragonite calcium carbonate nanocrystals (ANC) as a potential therapeutic and hormonal delivery vehicle for osteoporosis management. Free and human recombinant parathyroid hormone 1-34 (PTH 1-34)-loaded cockle shell aragonite calcium carbonate nanocrystals (PTH-ANC) were synthesized and evaluated using standard procedures. Transmission electron microscopy and field emission scanning electron microscopy results demonstrated highly homogenized spherical-shaped aragonite nanocrystals of 30±5 nm diameter. PTH-ANC had a zeta potential of -27.6±8.9 mV. The encapsulation efficiency of the formulation was found to be directly proportional to the concentrations of the drug fed. The X-ray diffraction patterns revealed strong crystallizations with no positional change of peaks before and after PTH-ANC synthesis. Fourier transform infrared spectroscopy demonstrated no detectable interactions between micron-sized aragonite and surfactant at molecular level. PTH-ANC formulation was stabilized at pH 7.5, enabling sustained slow release of PTH 1-34 for 168 h (1 week). A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cytocompatibility assay in Human Foetal Osteoblast Cell Line hFOB 1.19 showed that ANC can safely support osteoblast proliferation up to 48 h whereas PTH-ANC can safely support the proliferation at 72 h and beyond due to the sustained slow release of PTH 1-34. It was concluded that due to its biogenic nature, ANC is a cytocompatible antiosteoporotic agent. It doubles as a nanocarrier for the enhancement of efficacy and safety of the bone anabolic PTH 1-34. ANC is expected to reduce the cost, dosage, and dose frequency associated with the use of PTH 1-34 management of primary and secondary forms of osteoporosis.

  2. Chitosan/TPP Nanoparticles as a Gene Delivery Agent For Tumor Suppressant P53

    NASA Astrophysics Data System (ADS)

    Liu, Gaojun

    In the last decade, non-viral polymeric vectors have become more attractive than their viral counterparts due to their nontoxicity and good biocompatibility. However, one of the major drawbacks is the low transfection efficiency when compared to viruses. In this work, a naturally cationic polysaccharide, chitosan, was cross-linked with negatively charged tripolyphosphate (TPP) to synthesize chitosan/TPP nanoparticles (CNPs) for delivery of plasmid DNA (pDNA). Particle size and zeta potential were characterized for CNPs with chitosan-TPP mass ratios of 4:1 and 6:1 (w/w) using benchtop dynamic light scattering. And both potentiometric titration method and FTIR spectrometer were applied to measure the degree of deacetylation of chitosan. Release kinetics of a model protein (bovine serum albumin, BSA) showed a steady release that reached 7% after 6 days. Besides that, we also assessed the in vitro transfection efficiency of the CNP-pDNA system using fluorescence microscopy, as well as the effect of tumor suppressant p53. Later the release kinetics and encapsulation efficiency of plasmid DNA bound to the CNPs will be investigated. Additionally, we will try to improve the gene transfection efficiency in both MC3T3-E1 and osteosarcoma cells by applying Sonicator 740 therapeutic ultrasound. Key words: gene therapy, non-viral gene vector, chitosan/TPP nanoparticles, ionic gelation, p53.

  3. Methylselenocysteine - a Promising Antiangiogenic Agent for Overcoming Drug Delivery Barriers in Solid Malignancies for Therapeutic Synergy with Anticancer Drugs

    PubMed Central

    Bhattacharya, Arup

    2011-01-01

    Introduction Despite progress, chemotherapeutic response in solid malignancies has remained limited. While initial results of the use of antiangiogenic agents in combination chemotherapy indicated an enhanced therapeutic response, recent data indicates that the surviving cancer is not only able to surmount therapy, but is actually able to adapt a more aggressive metastatic phenotype. Thus, selecting an antiangiogenic agent that is less likely to lead to tumor resurgence is a key to future therapeutic success of antiangiogenic agents, in a combinatorial setting. Areas covered Against the broad spectrum of currently used antiangiogenic agents in the clinic, the putative benefits of the use of organo selenium (Se) compounds, such as methylselenocysteine (MSC), are discussed in this reiew. Expert opinion MSC, being part of the mammalian physiology, is a well tolerated, versatile and economical antiangiogenic agent. It down regulates multiple key upstream tumor survival markers, and enhances tumor drug delivery, at a given systemic dose of an anticancer agent, while protecting normal tissue from cytotoxic adverse effects. Further clinical trials, especially in poorly differentiated cancers, are warranted. PMID:21473705

  4. Lipid complexes with cationic peptides and OAKs; their role in antimicrobial action and in the delivery of antimicrobial agents.

    PubMed

    Epand, Raquel F; Mor, Amram; Epand, Richard M

    2011-07-01

    Antimicrobial agents are toxic to bacteria by a variety of mechanisms. One mechanism that is very dependent on the lipid composition of the bacterial membrane is the clustering of anionic lipid by cationic antimicrobial agents. Certain species of oligo-acyl-lysine (OAK) antimicrobial agents are particularly effective in clustering anionic lipids in mixtures mimicking the composition of bacterial membranes. The clustering of anionic lipids by certain cationic antimicrobial agents contributes to the anti-bacterial action of these agents. Bacterial membrane lipids are a determining factor, resulting in some species of bacteria being more susceptible than others. In addition, lipids can be used to increase the effectiveness of antimicrobial agents when administered in vivo. Therefore, we review some of the structures in which lipid mixtures can assemble, to more effectively be utilized as antimicrobial delivery systems. We describe in more detail the complexes formed between mixtures of lipids mimicking bacterial membranes and an OAK and their usefulness in synergizing with antibiotics to overcome bacterial multidrug resistance.

  5. Synthesis of Potential Prophylactic Agents against Cyanide Intoxication

    DTIC Science & Technology

    1993-04-12

    compiles th« synthetic procedures described in reports submitted for quarters 9-12 of this contract. We have also colligated structures of all...tingle example of ihn compound class was submitted for biological evaluation this report period, and the physical properties of this agent (1) are...condensation of propiophenone »ith diethyl oxalate (Eq. II) The physical properties of these compounds are summarized in Table 2. a cr, 3 F 4 OCH3 5 CH3

  6. Analogues of [(triethylsilyl)ethynyl]estradiol as potential antifertility agents.

    PubMed

    Peters, R H; Crowe, D F; Avery, M A; Chong, W K; Tanabe, M

    1988-03-01

    Various 17 alpha-ethynylsteroids were prepared and derivatized as the corresponding triethylsilyl compounds 2-35, which were examined for a ratio of antifertility to estrogenic activity that would be more beneficial than that of the presently used agent. Among the triethylsilyl compounds evaluated, only 23 displayed this desired ratio, although two other compounds without the triethylsilyl moiety, 18 and 26, shared similar characteristics.

  7. Antioxidants: potential antiviral agents for Japanese encephalitis virus infection.

    PubMed

    Zhang, Yu; Wang, Zehua; Chen, Huan; Chen, Zongtao; Tian, Yanping

    2014-07-01

    Japanese encephalitis (JE) is prevalent throughout eastern and southern Asia and the Pacific Rim. It is caused by the JE virus (JEV), which belongs to the family Flaviviridae. Despite the importance of JE, little is known about its pathogenesis. The role of oxidative stress in the pathogenesis of viral infections has led to increased interest in its role in JEV infections. This review focuses mainly on the role of oxidative stress in the pathogenesis of JEV infection and the antiviral effect of antioxidant agents in inhibiting JEV production. First, this review summarizes the pathogenesis of JE. The pathological changes include neuronal death, astrocyte activation, and microglial proliferation. Second, the relationship between oxidative stress and JEV infection is explored. JEV infection induces the generation of oxidants and exhausts the supply of antioxidants, which activates specific signaling pathways. Finally, the therapeutic efficacy of a variety of antioxidants as antiviral agents, including minocycline, arctigenin, fenofibrate, and curcumin, was studied. In conclusion, antioxidants are likely to be developed into antiviral agents for the treatment of JE. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. Nanomaterials as Non-viral siRNA Delivery Agents for Cancer Therapy

    PubMed Central

    Singh, Sanjay

    2013-01-01

    Gene therapy has been recently shown as a promising tool for cancer treatment as nanotechnology-based safe and effective delivery methods are developed. Generally, genes are wrapped up in extremely tiny nanoparticles which could be taken up easily by cancer cells, not to their healthy neighboring cells. Several nanoparticle systems have been investigated primarily to address the problems involved in other methods of gene delivery and observed improved anticancer efficacy suggesting that nanomedicine provides novel opportunities to safely deliver genes, thus treat cancer. In this review, various nanoparticle types and related strategies, used in gene delivery for cancer treatment, have been discussed. PMID:23878788

  9. Isolation of carbon nanohorn assemblies and their potential for intracellular delivery

    NASA Astrophysics Data System (ADS)

    Fan, Xiaobin; Tan, Juan; Zhang, Guoliang; Zhang, Fengbao

    2007-05-01

    Attributed to its distinctive dahlia-flowerlike structure and already desirable size (usually <100 nm), carbon nanohorn assemblies (CNHs), a new member of the fullerene family, are a potential vehicle for intracellular delivery. This paper shows that isolated CNHs and nanoscale CNH agglomerates can be successfully isolated by a copolymer (Gum Arabic) through steric stabilization. In vitro study shows that the modified CNHs are nontoxic and may be used as a promising vehicle for intracellular delivery.

  10. DNA electroporation of multi-agent vaccines conferring protection against select agent challenge: TriGrid delivery system.

    PubMed

    Keane-Myers, Andrea M; Bell, Matt; Hannaman, Drew; Albrecht, Mark

    2014-01-01

    Effective multi-agent/multivalent vaccines that confer protection against more than one disease are highly desirable to the patient and to health-care professionals. Electroporation of DNA vaccines, whereby tissues injected with DNA are subjected to localized electrical currents, is an ideal platform technology that achieves protective immune responses to multivalent vaccination. Here, we describe an electroporation-based immunization technique capable of administering a cocktail of DNA vaccinations in vivo. Immune response measurements, including protection from pathogen challenge and induction of antigen-specific antibody responses and cell-mediated immune responses, are also discussed.

  11. MR-Guided Delivery of Hydrophilic Molecular Imaging Agents Across the Blood-Brain Barrier Through Focused Ultrasound

    PubMed Central

    Airan, Raag D.; Foss, Catherine A.; Ellens, Nicholas P. K.; Wang, Yuchuan; Mease, Ronnie C.; Farahani, Keyvan; Pomper, Martin G.

    2016-01-01

    Purpose A wide variety of hydrophilic imaging and therapeutic agents are unable to gain access to the central nervous system (CNS) due to the blood-brain barrier (BBB). In particular, unless a particular transporter exists that may transport the agent across the BBB, most agents that are larger than 500 Da or that are hydrophilic will be excluded by the BBB. Glutamate carboxypeptidase II (GCPII), also known as the prostate-specific membrane antigen (PSMA) in the periphery, has been implicated in various neuropsychiatric conditions. As all agents that target GCPII are hydrophilic and thereby excluded from the CNS, we used GCPII as a platform for demonstrating our MR-guided focused ultrasound (MRgFUS) technique for delivery of GCPII/PSMA-specific imaging agents to the brain. Procedures Female rats underwent MRgFUS-mediated opening of the BBB. After opening of the BBB, either a radio- or fluorescently labeled ureido-based ligand for GCPII/PSMA was administered intravenously. Brain uptake was assessed for 2-(3-{1-carboxy-5-[(6-[18F]fluoropyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid ([18F]DCFPyL) and YC-27, two compounds known to bind GCPII/PSMA with high affinity, using positron emission tomography (PET) and near-infrared fluorescence (NIRF) imaging, respectively. Specificity of ligand binding to GCPII/PSMA in the brain was determined with co-administration of a molar excess of ZJ-43, a compound of the same chemical class but different structure from either [18F]DCFPyL or YC-27, which competes for GCPII/PSMA binding. Results Dynamic PET imaging using [18F]DCFPyL demonstrated that target uptake reached a plateau by ~1 h after radiotracer administration, with target/background ratios continuing to increase throughout the course of imaging, from a ratio of ~4:1 at 45 min to ~7:1 by 80 min. NIRF imaging likewise demonstrated delivery of YC-27 to the brain, with clear visualization of tracer in the brain at 24 h. Tissue uptake of both ligands was greatly

  12. Formulation development of smart gel periodontal drug delivery system for local delivery of chemotherapeutic agents with application of experimental design.

    PubMed

    Dabhi, Mahesh R; Nagori, Stavan A; Gohel, Mukesh C; Parikh, Rajesh K; Sheth, Navin R

    2010-01-01

    Smart gel periodontal drug delivery systems (SGPDDS) containing gellan gum (0.1-0.8% w/v), lutrol F127 (14, 16, and 18% w/v), and ornidazole (1% w/v) were designed for the treatment of periodontal diseases. Each formulation was characterized in terms of in vitro gelling capacity, viscosity, rheology, content uniformity, in vitro drug release, and syringeability. In vitro gelation time and the nature of the gel formed in simulated saliva for prepared formulations showed polymeric concentration dependency. Drug release data from all formulations was fitted to different kinetic models and the Korsemeyer-Peppas model was the best fit model. Drug release was significantly decreased as the concentration of each polymer component was increased. Increasing the concentration of each polymeric component significantly increased viscosity, syringeability, and time for 50%, 70%, and 90% drug release. In conclusion, the formulations described offer a wide range of physical and drug release characteristics. The formulation containing 0.8% w/v of gellan gum and 16% w/v of lutrol F127 exhibited superior physical characteristics.

  13. Ionic liquids as potential enhancers for transdermal drug delivery.

    PubMed

    Monti, Daniela; Egiziano, Emanuele; Burgalassi, Susi; Chetoni, Patrizia; Chiappe, Cinzia; Sanzone, Angelo; Tampucci, Silvia

    2017-01-10

    The aim of this study was to verify the effect of several cyclic onium based ionic liquids (ILs), including mono- and dicationic derivatives of 1,4-diazabicyclo[2.2.2]octane (DABCO), a dialkyl morpholinium salt and a Brønsted acidic IL, as enhancers of the in vitro transdermal permeation and skin retention of diltiazem through and into hairless rat skin. The drug was used as both the hydrochloride salt (DZHCl) and the free base (DZB) to highlight the relationship between the enhancement effect and the physico-chemical characteristics of the active agent. Permeation tests were carried out using Gummer-type diffusion cells and excised rat skin with a 0.005M aqueous solution of diltiazem hydrochloride or diltiazem free base with and without the addition of 1% w/w ionic liquids. At the end of the permeation experiments with diltiazem hydrochloride, a suitable extraction procedure allowed for the determination of the drug content retained in the skin. Depending on the ionic liquid structure, a significant enhancement in diltiazem hydrochloride levels in the receiving phase was observed, and the transdermal permeation of the diltiazem free base was markedly increased by treatment with all of the ionic liquids. N-dodecyldabco bromide was the best enhancer for both salified and free base drug forms, even though it showed a certain toxicity. On the other hand, N-methyl-N-decylmorpholinium bromide showed a good balance between enhancer activity and cytotoxicity. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Vendors and Delivery: An Analysis of Selected Publishers, Publisher/Agents, Distributors, and Wholesalers

    ERIC Educational Resources Information Center

    Lincoln, Robert

    1978-01-01

    By using computer-stored data, acquisitions librarians can have access to vendor, book, and trade information. Tables compiled from such data show delivery times on orders from each Canadian vendor surveyed by publisher type and year. (JAB)

  15. Microtubule-Stabilizing Agents as Potential Therapeutics for Neurodegenerative Disease

    PubMed Central

    Brunden, Kurt R.; Trojanowski, John Q.; Smith, Amos B.; Lee, Virginia M.-Y.; Ballatore, Carlo

    2014-01-01

    Microtubules (MTs)1, cytoskeletal elements found in all mammalian cells, play a significant role in cell structure and in cell division. They are especially critical in the proper functioning of post-mitotic central nervous system neurons, where MTs serve as the structures on which key cellular constituents are trafficked in axonal projections. MTs are stabilized in axons by the MT-associated protein tau, and in several neurodegenerative diseases, including Alzheimer’s disease, frontotemporal lobar degeneration, and Parkinson’s disease, tau function appears to be compromised due to the protein dissociating from MTs and depositing into insoluble inclusions referred to as neurofibrillary tangles. This loss of tau function is believed to result in alterations of MT structure and function, resulting in aberrant axonal transport that likely contributes to the neurodegenerative process. There is also evidence of axonal transport deficiencies in other neurodegenerative diseases, including amyotrophic lateral sclerosis and Huntington’s disease, which may result, at least in part, from MT alterations. Accordingly, a possible therapeutic strategy for such neurodegenerative conditions is to treat with MT-stabilizing agents, such as those that have been used in the treatment of cancer. Here, we review evidence of axonal transport and MT deficiencies in a number of neurodegenerative diseases, and summarize the various classes of known MT-stabilizing agents. Finally, we highlight the growing evidence that small molecule MT-stabilizing agents provide benefit in animal models of neurodegenerative disease and discuss the desired features of such molecules for the treatment of these central nervous system disorders. PMID:24433963

  16. Microtubule-stabilizing agents as potential therapeutics for neurodegenerative disease.

    PubMed

    Brunden, Kurt R; Trojanowski, John Q; Smith, Amos B; Lee, Virginia M-Y; Ballatore, Carlo

    2014-09-15

    Microtubules (MTs), cytoskeletal elements found in all mammalian cells, play a significant role in cell structure and in cell division. They are especially critical in the proper functioning of post-mitotic central nervous system neurons, where MTs serve as the structures on which key cellular constituents are trafficked in axonal projections. MTs are stabilized in axons by the MT-associated protein tau, and in several neurodegenerative diseases, including Alzheimer's disease, frontotemporal lobar degeneration, and Parkinson's disease, tau function appears to be compromised due to the protein dissociating from MTs and depositing into insoluble inclusions referred to as neurofibrillary tangles. This loss of tau function is believed to result in alterations of MT structure and function, resulting in aberrant axonal transport that likely contributes to the neurodegenerative process. There is also evidence of axonal transport deficiencies in other neurodegenerative diseases, including amyotrophic lateral sclerosis and Huntington's disease, which may result, at least in part, from MT alterations. Accordingly, a possible therapeutic strategy for such neurodegenerative conditions is to treat with MT-stabilizing agents, such as those that have been used in the treatment of cancer. Here, we review evidence of axonal transport and MT deficiencies in a number of neurodegenerative diseases, and summarize the various classes of known MT-stabilizing agents. Finally, we highlight the growing evidence that small molecule MT-stabilizing agents provide benefit in animal models of neurodegenerative disease and discuss the desired features of such molecules for the treatment of these central nervous system disorders. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Photosensitive liposomes as potential drug delivery vehicles for photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Morgan, Christopher G.; Mitchell, A. C.; Chowdhary, R. K.

    1991-11-01

    Light-sensitive liposomes incorporating a photochromic phospholipid (Bis-Azo PC) have been developed which exhibit light-activated release of entrapped contents and intervesicular fusion. The trapping and light-induced release of inorganic ions, fluorescent market dyes, and the antitumor drug methotrexate have been demonstrated. These results are discussed together with some of the potential therapeutic applications of light-sensitive liposomes.

  18. Monocarboxylate Transporter 1 Inhibitors as Potential Anticancer Agents

    PubMed Central

    2015-01-01

    Potent monocarboxylate transporter 1 inhibitors (MCT1) have been developed based on α-cyano-4-hydroxycinnamic acid template. Structure–activity relationship studies demonstrate that the introduction of p-N, N-dialkyl/diaryl, and o-methoxy groups into cyanocinnamic acid has maximal MCT1 inhibitory activity. Systemic toxicity studies in healthy ICR mice with few potent MCT1 inhibitors indicate normal body weight gains in treated animals. In vivo tumor growth inhibition studies in colorectal adenocarcinoma (WiDr cell line) in nude mice xenograft models establish that compound 27 exhibits single agent activity in inhibiting the tumor growth. PMID:26005533

  19. Monocarboxylate transporter 1 inhibitors as potential anticancer agents.

    PubMed

    Gurrapu, Shirisha; Jonnalagadda, Sravan K; Alam, Mohammad A; Nelson, Grady L; Sneve, Mary G; Drewes, Lester R; Mereddy, Venkatram R

    2015-05-14

    Potent monocarboxylate transporter 1 inhibitors (MCT1) have been developed based on α-cyano-4-hydroxycinnamic acid template. Structure-activity relationship studies demonstrate that the introduction of p-N, N-dialkyl/diaryl, and o-methoxy groups into cyanocinnamic acid has maximal MCT1 inhibitory activity. Systemic toxicity studies in healthy ICR mice with few potent MCT1 inhibitors indicate normal body weight gains in treated animals. In vivo tumor growth inhibition studies in colorectal adenocarcinoma (WiDr cell line) in nude mice xenograft models establish that compound 27 exhibits single agent activity in inhibiting the tumor growth.

  20. Non-peptidyl insulin mimetics as a potential antidiabetic agent.

    PubMed

    Nankar, Rakesh P; Doble, Mukesh

    2013-08-01

    Insulin has an important role in the maintenance of blood sugar. It is the only available therapeutic agent for the treatment of type 1 diabetes mellitus and there is a dire need for an oral substitute. Different categories of compounds including mono and di substituted benzoquinones, vanadium based compounds and natural products have been reported to cause insulin-like effects either by increasing phosphorylation of insulin receptor (IR) or inhibiting the protein tyrosine phosphatases. This review summarizes the development of various insulin mimetics with special emphasis on their structure-activity relationships and various biological actions they produce.

  1. Investigation of Vietnamese plants for potential anticancer agents

    PubMed Central

    Pérez, Lynette Bueno; Still, Patrick C.; Naman, C. Benjamin; Ren, Yulin; Pan, Li; Chai, Hee-Byung; Carcache de Blanco, Esperanza J.; Ninh, Tran Ngoc; Van Thanh, Bui; Swanson, Steven M.; Soejarto, Djaja D.

    2014-01-01

    Higher plants continue to afford humankind with many new drugs, for a variety of disease types. In this review, recent phytochemical and biological progress is presented for part of a collaborative multi-institutional project directed towards the discovery of new antitumor agents. The specific focus is on bioactive natural products isolated and characterized structurally from tropical plants collected in Vietnam. The plant collection, identification, and processing steps are described, and the natural products isolated from these species are summarized with their biological activities. PMID:25395897

  2. Cervical ripening agent dinoprostone for delivery induction in late pregnancy mothers: experiences of 685 cases.

    PubMed

    Liang, C; Xu, D; He, J

    2015-01-01

    The failure of labor induction often requires following cesarean section and suffering of patients. Cervical ripening is therefore critical in clinical care of pregnant mothers. The present study demonstrated the use of dinoprostone in cervical ripening for delivery induction in 685 cases of pregnancy mothers. The authors conclude that dinoprostone is a very useful and safe drug for delivery induction. The combined use of oxytocin and careful monitoring of all body symptoms are important for the clinical safety.

  3. Handheld Delivery System for Modified Boron-Type Fire Extinguishment Agent

    DTIC Science & Technology

    1993-11-01

    TMB reduces this reaction; however, during storage the agent must still be isolated from any moisture source. The white precipitate is oily and gummy to...final design was goverened by the characteristics of the agent itself. Since Boralon will form a white, gummy percipitate when exposed to atmospheric...MIL-F-2261A Fire Extinguishing Agent, Liquid, Boron-Type, for Metal Fires MIL-B-26195 Box, Wood, Cleated, Skidded, Load Bearing Base 37 MIL-F-XXXX

  4. Pyrazoles as potential anti-angiogenesis agents: a contemporary overview

    PubMed Central

    Kasiotis, Konstantinos M.; Tzanetou, Evangelia N.; Haroutounian, Serkos A.

    2014-01-01

    Angiogenesis is a mulit-step process by which new blood vessels are formed from preexisting vasculature. It is a key rate limiting factor in tumor growth since new blood vessels are necessary to increase tumor size. In this context it has been shown that anti-angiogenic factors can be used in cancer therapy. Among the plethora of heterocyclic compounds administered as anti-angiogenesis agents, pyrazoles constitute one of the bottlenecks of this category. Currently, several pyrazole based compounds are administered or are in Phase II and III trials and new targets emerge. It is highly possible that the advent of the next two decades will lead to the discovery and use of additional pyrazoles whose anti-angiogenic profile will position them in the forefront of the battle of various malignancies. The present review is an attempt to focus on those pyrazoles that arise as anti-angiogenesis agents commenting both on the chemistry and bioactivity that these exhibit aiming to contribute to the perspectives that they hold for future research. PMID:25250310

  5. Ginsenoside Rd as a potential neuroprotective agent prevents trimethyltin injury

    PubMed Central

    Hou, Jingang; Xue, Jianjie; Lee, Mira; Sung, Changkeun

    2017-01-01

    Trimethyltin (TMT) is a potent neurotoxicant that affects various regions within the central nervous system, including the neocortex, cerebellum, and hippocampus. In the present study, ginsenoside Rd was investigated as a candidate neuroprotective agent in a primary hippocampal neuron culture and mouse models. TMT induced neurotoxicity in a seven-day primary hippocampal neuron culture in a dose-dependent manner (2.5–10 µM). However, pre-treatment with 20 µg/ml ginsenoside Rd for 24 h reversed the toxic action. ICR mice were administered a single injection of 2 mg/kg body weight TMT. Apparent tremor seizure and impaired passive avoidance tests demonstrated significant differences when compared with a saline treated control group. Nissl staining was performed to evaluate the neuronal loss in the hippocampus. In addition, immunostaining of glial fibrillary acidic protein characterized the features of astroglial activation. These results demonstrated that TMT markedly induced Cornu Ammonis 1 subregion neuronal loss and reactive astrocytes in the hippocampus, indicating disrupted hippocampal function. Notably, ginsenoside Rd attenuated the tremor seizures and cognitive decline in behavioral tests. Additionally, significantly reduced neuronal loss (P=0.018) and active astroglials (P=0.003) were observed in the ginsenoside Rd treated group. Ginsenoside Rd prevented TMT-induced cell apoptosis via regulation of B-cell lymphoma 2 (Bcl-2), bcl-2-like protein 4 and caspase-3. These results demonstrate that ginsenoside may be developed as a neuroprotective agent to prevent TMT-induced neurotoxicity. PMID:28413642

  6. Synthetic antiferromagnetic nanoparticles as potential contrast agents in MRI.

    PubMed

    Van Roosbroeck, Ruben; Van Roy, Willem; Stakenborg, Tim; Trekker, Jesse; D'Hollander, Antoine; Dresselaers, Tom; Himmelreich, Uwe; Lammertyn, Jeroen; Lagae, Liesbet

    2014-03-25

    We present the top-down synthesis of a novel type of MRI T2 contrast agent with great control over size and shape using a colloidal lithography technique. The resulting synthetic antiferromagnetic nanoparticles (SAF-NPs) yield improved relaxivities compared to superparamagnetic iron oxide alternatives (SPIONs). For T2 weighted imaging, the outer sphere relaxation theory has shown that the sensitivity of a T2 contrast agent is dependent on the particle size with an optimal size that exceeds the superparamagnetic limit of SPIONs. With the use of the interlayer exchange coupling effect, the SAF-NPs presented here do not suffer from this limit. Adjusting the outer sphere relaxation theory for spherical particles to SAF-NPs, we show both theoretically and experimentally that the SAF-NP size can be optimized to reach the r2 maximum. With measured r2 values up to 355 s(-1) mM(-1), our SAF-NPs show better performance than commercial alternatives and are competitive with the state-of-the-art. This performance is confirmed in an in vitro MRI study on SKOV3 cells.

  7. Pyrazoles as potential anti-angiogenesis agents: A contemporary overview

    NASA Astrophysics Data System (ADS)

    Kasiotis, Konstantinos; Tzanetou, Evangelia; Haroutounian, Serkos

    2014-09-01

    Angiogenesis is a mulit-step process by which new blood vessels are formed from preexisting vasculature. It is a key rate limiting factor in tumor growth since new blood vessels are necessary to increase tumor size. In this context it has been shown that anti-angiogenic factors can be used in cancer therapy. Among the plethora of heterocyclic compounds administered as anti-angiogenesis agents, pyrazoles constitute one of the bottlenecks of this category. Currently several pyrazole based compounds are administered or are in Phase II and III trials and new targets emerge. It is highly possible that the advent of the next two decades will lead to the discovery and use of additional pyrazoles whose anti-angiogenic profile will position them in the forefront of the battle of various malignancies. The present review is an attempt to focus on those pyrazoles that arise as anti-angiogenesis agents commenting both on the chemistry and bioactivity that these exhibit aiming to contribute to the perspectives that they hold for future research.

  8. Mesoporous silica nanoparticles with organo-bridged silsesquioxane framework as innovative platforms for bioimaging and therapeutic agent delivery.

    PubMed

    Du, Xin; Li, Xiaoyu; Xiong, Lin; Zhang, Xueji; Kleitz, Freddy; Qiao, Shi Zhang

    2016-06-01

    Mesoporous silica material with organo-bridged silsesquioxane frameworks is a kind of synergistic combination of inorganic silica, mesopores and organics, resulting in some novel or enhanced physicochemical and biocompatible properties compared with conventional mesoporous silica materials with pure Si-O composition. With the rapid development of nanotechnology, monodispersed nanoscale periodic mesoporous organosilica nanoparticles (PMO NPs) and organo-bridged mesoporous silica nanoparticles (MSNs) with various organic groups and structures have recently been synthesized from 100%, or less, bridged organosilica precursors, respectively. Since then, these materials have been employed as carrier platforms to construct bioimaging and/or therapeutic agent delivery nanosystems for nano-biomedical application, and they demonstrate some unique and/or enhanced properties and performances. This review article provides a comprehensive overview of the controlled synthesis of PMO NPs and organo-bridged MSNs, physicochemical and biocompatible properties, and their nano-biomedical application as bioimaging agent and/or therapeutic agent delivery system. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Superparamagnetic bifunctional bisphosphonates nanoparticles: a potential MRI contrast agent for osteoporosis therapy and diagnostic.

    PubMed

    Lalatonne, Y; Monteil, M; Jouni, H; Serfaty, J M; Sainte-Catherine, O; Lièvre, N; Kusmia, S; Weinmann, P; Lecouvey, M; Motte, L

    2010-06-15

    A bone targeting nanosystem is reported here which combined magnetic contrast agent for Magnetic Resonance Imaging (MRI) and a therapeutic agent (bisphosphonates) into one drug delivery system. This new targeting nanoplatform consists of superparamagnetic γFe(2)O(3) nanoparticles conjugated to 1,5-dihydroxy-1,5,5-tris-phosphono-pentyl-phosphonic acid (di-HMBPs) molecules with a bisphosphonate function at the outer of the nanoparticle surface for bone targeting. The as-synthesized nanoparticles were evaluated as a specific MRI contrast agent by adsorption study onto hydroxyapatite and MRI measurment. The strong adsorption of the bisphosphonates nanoparticles to hydroxyapatite and their use as MRI T2(∗) contrast agent were demonstrated. Cellular tests performed on human osteosarcoma cells (MG63) show that γFe(2)O(3)@di-HMBP hybrid nanomaterial has no citoxity effect in cell viability and may act as a diagnostic and therapeutic system.

  10. Superparamagnetic Bifunctional Bisphosphonates Nanoparticles: A Potential MRI Contrast Agent for Osteoporosis Therapy and Diagnostic

    PubMed Central

    Lalatonne, Y.; Monteil, M.; Jouni, H.; Serfaty, J. M.; Sainte-Catherine, O.; Lièvre, N.; Kusmia, S.; Weinmann, P.; Lecouvey, M.; Motte, L.

    2010-01-01

    A bone targeting nanosystem is reported here which combined magnetic contrast agent for Magnetic Resonance Imaging (MRI) and a therapeutic agent (bisphosphonates) into one drug delivery system. This new targeting nanoplatform consists of superparamagnetic γFe2O3 nanoparticles conjugated to 1,5-dihydroxy-1,5,5-tris-phosphono-pentyl-phosphonic acid (di-HMBPs) molecules with a bisphosphonate function at the outer of the nanoparticle surface for bone targeting. The as-synthesized nanoparticles were evaluated as a specific MRI contrast agent by adsorption study onto hydroxyapatite and MRI measurment. The strong adsorption of the bisphosphonates nanoparticles to hydroxyapatite and their use as MRI T2∗ contrast agent were demonstrated. Cellular tests performed on human osteosarcoma cells (MG63) show that γFe2O3@di-HMBP hybrid nanomaterial has no citoxity effect in cell viability and may act as a diagnostic and therapeutic system. PMID:20981332

  11. Targeted delivery of 5-fluorouracil to cholangiocarcinoma cells using folic acid as a targeting agent.

    PubMed

    Ngernyuang, Nipaporn; Seubwai, Wunchana; Daduang, Sakda; Boonsiri, Patcharee; Limpaiboon, Temduang; Daduang, Jureerut

    2016-03-01

    There are limits to the standard treatment for cholangiocarcinoma (CCA) including drug resistance and side effects. The objective of this study was to develop a new technique for carrying drugs by conjugation with gold nanoparticles and using folic acid as a targeting agent in order to increase drug sensitivity. Gold nanoparticles (AuNPs) were functionalized with 5-fluorouracil (5FU) and folic acid (FA) using polyethylene glycol (PEG) shell as a linker (AuNPs-PEG-5FU-FA). Its cytotoxicity was tested in CCA cell lines (M139 and M213) which express folic acid receptor (FA receptor). The results showed that AuNPs-PEG-5FU-FA increased the cytotoxic effects in the M139 and M213 cells by 4.76% and 7.95%, respectively compared to those treated with free 5FU+FA. It is found that the cytotoxicity of the AuNPs-PEG-5FU-FA correlates with FA receptor expression suggested the use of FA as a targeted therapy. The mechanism of cytotoxicity was mediated via mitochondrial apoptotic pathway as determined by apoptosis array. In conclusion, our findings shed some light on the use of gold nanoparticles for conjugation with potential compounds and FA as targeted therapy which contribute to the improvement of anti-cancer drug efficacy. In vivo study should be warranted for its effectiveness of stability, biosafety and side effect reduction.

  12. Therapeutic Potential of Hydrazones as Anti-Inflammatory Agents

    PubMed Central

    Bala, Suman; Sharma, Neha; Saini, Vipin

    2014-01-01

    Hydrazones are a special class of organic compounds in the Schiff base family. Hydrazones constitute a versatile compound of organic class having basic structure (R1R2C=NNR3R4). The active centers of hydrazone, that is, carbon and nitrogen, are mainly responsible for the physical and chemical properties of the hydrazones and, due to the reactivity toward electrophiles and nucleophiles, hydrazones are used for the synthesis of organic compound such as heterocyclic compounds with a variety of biological activities. Hydrazones and their derivatives are known to exhibit a wide range of interesting biological activities like antioxidant, anti-inflammatory, anticonvulsant, analgesic, antimicrobial, anticancer, antiprotozoal, antioxidant, antiparasitic, antiplatelet, cardioprotective, anthelmintic, antidiabetic, antitubercular, trypanocidal, anti-HIV, and so forth. The present review summarizes the efficiency of hydrazones as potent anti-inflammatory agents. PMID:25383223

  13. Ag+ complexes as potential therapeutic agents in medicine and pharmacy.

    PubMed

    Hecel, Aleksandra; Kolkowska, Paulina; Krzywoszynska, Karolina; Szebesczyk, Agnieszka; Rowinska-Zyrek, Magdalena; Kozlowski, Henryk

    2017-09-20

    Silver is a non-essential element, with promising antimicrobial and anticancer properties. This work is a detailed summary of the newest findings on the bioinorganic chemistry of silver, with a special focus on the applications of Ag+ complexes and nanoparticles. The coordination chemistry of silver is given a reasonable amount of attention, summarizing the most common silver binding sites and giving examples of such binding motifs in biologically important proteins. Possible applications of this metal and its complexes in medicine, in particular as antibacterial and antifungal agents and in cancer therapy is discussed in detail. The most recent data on silver nanoparticles are also summarized. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  14. Potential radiosensitizing agents. 5. 2-Substituted benzimidazole derivatives

    SciTech Connect

    Gupta, R.P.; Larroquette, C.A.; Agrawal, K.C.

    1982-11-01

    A series of 2-substituted benzimidazoles and their derivatives have been synthesized and tested for their ability to selectively sensitize hypoxic Chinese hamster cells (V-79) toward the lethal effect of ionizing radiation. These compounds were prepared by reacting the 2-substituted benzimidazoles with 1,2-epoxy-3-methoxypropane in the presence of potassium carbonate. Reaction of the 2-nitro and 2-methylfonyl analogue with the epoxide also yielded a cyclized material, which was confirmed to be a benzimidazo(2,1-b)oxazole. In an attempt to increase the electron affinity, 5- or 6-nitro-2-substituted-benzimidazoles were also synthesized and then reacted with the epoxide to yield the corresponding 1-substituted derivatives. The results of the biological tests for the radiosensitizing activity of these agents against Chinese hamster cells (V-79) in culture indicated that the 2-nitro-substituted analogues were the most effective sensitizers in this series.

  15. Delivery of therapeutic radioisotopes using nanoparticle platforms: potential benefit in systemic radiation therapy

    PubMed Central

    Zhang, Longjiang; Chen, Hongwei; Wang, Liya; Liu, Tian; Yeh, Julie; Lu, Guangming; Yang, Lily; Mao, Hui

    2010-01-01

    Radiation therapy is an effective cancer treatment option in conjunction with chemotherapy and surgery. Emerging individualized internal and systemic radiation treatment promises significant improvement in efficacy and reduction of normal tissue damage; however, it requires cancer cell targeting platforms for efficient delivery of radiation sources. With recent advances in nanoscience and nanotechnology, there is great interest in developing nanomaterials as multifunctional carriers to deliver therapeutic radioisotopes for tumor targeted radiation therapy, to monitor their delivery and tumor response to the treatment. This paper provides an overview on developing nanoparticles for carrying and delivering therapeutic radioisotopes for systemic radiation treatment. Topics discussed in the review include: selecting nanoparticles and radiotherapy isotopes, strategies for targeting nanoparticles to cancers, together with challenges and potential solutions for the in vivo delivery of nanoparticles. Some examples of using nanoparticle platforms for the delivery of therapeutic radioisotopes in preclinical studies of cancer treatment are also presented. PMID:24198480

  16. Enteric MRI contrast agents: comparative study of five potential agents in humans.

    PubMed

    Tart, R P; Li, K C; Storm, B L; Rolfes, R J; Ang, P G

    1991-01-01

    We compared the effectiveness of 1 mM Geritol, 12% corn oil emulsion, Kaolin-pectin, single contrast oral barium sulfate, and effervescent granules as enteric magnetic resonance imaging (MRI) contrast agents. Five volunteers were recruited. Each volunteer ingested for examinations, separated by at least one week, either 500 ml of each of the liquid preparations or two packets of the CO2 granules (producing 400 ml of CO2 per packet). Abdominal MR images were then obtained using a 1.5 T Magnetom imager and SE 550/22, SE 2000/45/90 and FISP 40/18/40 degrees pulse sequences. The oil emulsions were best tolerated. Barium sulfate caused the greatest amount of nausea, followed by Geritol and Kaolin-pectin. With FISP 40/18/40 degrees, 60%-80% of the small bowel was well delineated using oil emulsion, Kaolin-pectin, or barium sulfate. We conclude that oil emulsion was by far the best enteric MR contrast agent in our study. Good delineation of the small bowel and pancreas can be achieved using oil emulsion and gradient echo pulse sequences. The lack of side-effects and the excellent taste make it highly acceptable to human subjects.

  17. Structure-function investigations of DNA condensing agents with application to gene delivery

    NASA Astrophysics Data System (ADS)

    Evans, Heather Marie

    Lipid-based systems are notoriously poor for gene delivery, and their use has been primarily empirical. In order to improve these systems, it is imperative to obtain a greater understanding of molecular interactions between DNA and positively charged molecules. A variety of cationic molecules have been studied with DNA, in an attempt to correlate structural properties of these assemblies (using x-ray diffraction) with their efficiency as DNA carriers for gene delivery (using a luciferase assay). Several systems have been studied, some of which use the same charged amine moieties presented in three distinct morphologies: the multivalent salts spermine and spermidine, dendrimers, and dendrimeric lipids. The dendrimers somewhat approximate the properties of histories, cylindrical proteins that condense intracellular DNA. Structural studies of histone and DNA have also been conducted in order to better understand these interactions and their possible relevance to the gene delivery pathway. In addition, empirical evidence suggests that for successful in vivo gene delivery, cholesterol should be used as a helper lipid. The delivery efficiency and structural behavior of cholesterol and other sterol molecules have been studied in ternary lipid mixtures.

  18. Sublingual Delivery of Frovatriptan: An Indication of Potential Alternative Route

    PubMed Central

    Verma, Surajpal; Prasad, Shyam Baboo

    2014-01-01

    Frovatriptan, a 5-HT1B and 5-HT1D receptor agonist, is used for the treatment of acute migraine attack. This molecule is classified into second line therapy because of its slow onset of action (peak response obtained after 4 hours of administration) and low bioavailability (25%). Moreover, its therapy is the most costly among all triptans. Attempt has been made in present work to suggest a way out to fasten its onset of action and to enhance its bioavailability. Prepared tablets were evaluated by physicochemical tests, in vitro permeation studies, ex vivo permeation studies, and histopathological studies. Suitable mathematical calculations were performed to calculate the minimum amount of bioavailability that could be enhanced. Tablets containing chitosan (5% w/w) were found to give optimum results. Prepared tablets can double the bioavailability of frovatriptan and can initiate its response within 10 minutes of its administration. Suggestive alternative has the potential to increase the efficacy of frovatriptan for treating acute migraine attack. PMID:27433492

  19. Sublingual Delivery of Frovatriptan: An Indication of Potential Alternative Route.

    PubMed

    Verma, Hitesh; Verma, Surajpal; Prasad, Shyam Baboo; Singh, Harmanpreet

    2014-01-01

    Frovatriptan, a 5-HT1B and 5-HT1D receptor agonist, is used for the treatment of acute migraine attack. This molecule is classified into second line therapy because of its slow onset of action (peak response obtained after 4 hours of administration) and low bioavailability (25%). Moreover, its therapy is the most costly among all triptans. Attempt has been made in present work to suggest a way out to fasten its onset of action and to enhance its bioavailability. Prepared tablets were evaluated by physicochemical tests, in vitro permeation studies, ex vivo permeation studies, and histopathological studies. Suitable mathematical calculations were performed to calculate the minimum amount of bioavailability that could be enhanced. Tablets containing chitosan (5% w/w) were found to give optimum results. Prepared tablets can double the bioavailability of frovatriptan and can initiate its response within 10 minutes of its administration. Suggestive alternative has the potential to increase the efficacy of frovatriptan for treating acute migraine attack.

  20. Engineering Design and Molecular Dynamics of Mucoadhesive Drug Delivery Systems as Targeting Agents

    PubMed Central

    Serra, Laura; Doménech, Josep; Peppas, Nicholas

    2009-01-01

    The goal of this critical review is to provide a critical analysis of the chain dynamics responsible for the action of micro- and nanoparticles of mucoadhesive biomaterials. The objective of using bioadhesive controlled drug delivery devices is to prolong their residence at a specific site of delivery, thus enhancing the drug absorption process. These mucoadhesive devices can protect the drug during the absorption process in addition to protecting it on its route to the delivery site. The major emphasis of recent research on mucoadhesive biomaterials has been on the use of adhesion promoters, which would enhance the adhesion between synthetic polymers and mucus. The use of adhesion promoters such as linear or tethered polymer chains is a natural result of the diffusional characteristics of adhesion. Mucoadhesion depends largely on the structure of the synthetic polymer gels used in controlled release applications. PMID:18976706

  1. Neem components as potential agents for cancer prevention and treatment

    PubMed Central

    Hao, Fang; Kumar, Sandeep; Yadav, Neelu; Chandra, Dhyan

    2016-01-01

    Azadirachta indica, also known as neem, is commonly found in many semi-tropical and tropical countries including India, Pakistan, and Bangladesh. The components extracted from neem plant have been used in traditional medicine for the cure of multiple diseases including cancer for centuries. The extracts of seeds, leaves, flowers, and fruits of neem have consistently shown chemopreventive and antitumor effects in different types of cancer. Azadirachtin and nimbolide are among the few bioactive components in neem that have been studied extensively, but research on a great number of additional bioactive components is warranted. The key anticancer effects of neem components on malignant cells include inhibition of cell proliferation, induction of cell death, suppression of cancer angiogenesis, restoration of cellular reduction/oxidation (redox) balance, and enhancement of the host immune responses against tumor cells. While the underlying mechanisms of these effects are mostly unclear, the suppression of NF-κB signaling pathway is, at least partially, involved in the anticancer functions of neem components. Importantly, the anti-proliferative and apoptosis-inducing effects of neem components are tumor selective as the effects on normal cells are significantly weaker. In addition, neem extracts sensitize cancer cells to immunotherapy and radiotherapy, and enhance the efficacy of certain cancer chemotherapeutic agents. This review summarizes the current updates on the anticancer effects of neem components and their possible impact on managing cancer incidence and treatment. PMID:25016141

  2. Novel Oxadiazole Thioglycosides as Potential Anti-Acinetobacter Agents

    PubMed Central

    Akbari Dilmaghani, Karim; Nasuhi Pur, Fazel; Mahammad pour, Majid; Mahammad nejad, Jafar

    2016-01-01

    The glycosylation of 1,3,4-oxadiazole-2-thiones has been performed with peracetylated β-pyranosyl bromide in the presence of potassium carbonate. Deprotection of acetylated thioglycosides was necessary for increasing their antibacterial effects. The structures of nucleosides were confirmed by 1H NMR, 13C NMR and HRMS. The anomeric protons of nucleosides c1–4 were assigned to the doublet, confirming the β-configuration. The synthesized compounds were tested for their antimicrobial activity against Acinetobacter calcoaceticus (Gram-negetive) strain in-vitro in comparison with Ampicillin as a reference drug which is normally used for treating such infections. The synthetic compounds showed different inhibition zones against tested bacterial strain. Thioglycoside derivatives of 1,3,4-oxadiazole-2-thiones (c set) were more active against Acinetobacter calcoaceticus ATCC 23055 than “parent” 1,3,4-oxadiazole-2-thiones (a set), confirming the relation between glyco-conjugation and increasing of antiproliferative activity of antibiotic agents. The best result belonged to nucleoside bearing 2-furyl moiety in its heterocyclic nucleus (c4). The existence of m-PhNO2 group as Ar in structures of a set and their corresponding sugar derivatives decreased the antibacterial activity of them in comparison with the rest of synthetic compounds. PMID:28243273

  3. Thymol and eugenol derivatives as potential antileishmanial agents.

    PubMed

    de Morais, Selene Maia; Vila-Nova, Nadja Soares; Bevilaqua, Claudia Maria Leal; Rondon, Fernanda Cristina; Lobo, Carlos Henrique; de Alencar Araripe Noronha Moura, Arlindo; Sales, Antônia Débora; Rodrigues, Ana Paula Ribeiro; de Figuereido, José Ricardo; Campello, Claudio Cabral; Wilson, Mary E; de Andrade, Heitor Franco

    2014-11-01

    In Northeastern Brazil visceral leishmaniasis is endemic with lethal cases among humans and dogs. Treatment is toxic and 5-10% of humans die despite treatment. The aim of this work was to survey natural active compounds to find new molecules with high activity and low toxicity against Leishmania infantum chagasi. The compounds thymol and eugenol were chosen to be starting compounds to synthesize acetyl and benzoyl derivatives and to test their antileishmanial activity in vitro and in vivo against L. i. chagasi. A screening assay using luciferase-expressing promastigotes was used to measure the growth inhibition of promastigotes, and an ELISA in situ was performed to evaluate the growth inhibition of amastigote. For the in vivo assay, thymol and eugenol derivatives were given IP to BALB/c mice at 100mg/kg/day for 30 days. The thymol derivatives demonstrated the greater activity than the eugenol derivatives, and benzoyl-thymol was the best inhibitor (8.67 ± 0.28 μg/mL). All compounds demonstrated similar activity against amastigotes, and acetyl-thymol was more active than thymol and the positive control drug amphotericin B. Immunohistochemistry demonstrated the presence of Leishmania amastigote only in the spleen but not the liver of mice treated with acetyl-thymol. Thus, these synthesized derivatives demonstrated anti-leishmanial activity both in vitro and in vivo. These may constitute useful compounds to generate new agents for treatment of leishmaniasis.

  4. Thymol and eugenol derivatives as potential antileishmanial agents

    PubMed Central

    de Morais, Selene Maia; Vila-Nova, Nadja Soares; Bevilaqua, Claudia Maria Leal; Rondon, Fernanda Cristina; Lobo, Carlos Henrique; de Alencar Araripe Noronha Moura, Arlindo; Sales, Antônia Débora; Rodrigues, Ana Paula Ribeiro; de Figuereido, José Ricardo; Campello, Claudio Cabral; Wilson, Mary E.; de Andrade, Heitor Franco

    2016-01-01

    In Northeastern Brazil visceral leishmaniasis is endemic with lethal cases among humans and dogs. Treatment is toxic and 5–10% of humans die despite treatment. The aim of this work was to survey natural active compounds to find new molecules with high activity and low toxicity against Leishmania infantum chagasi. The compounds thymol and eugenol were chosen to be starting compounds to synthesize acetyl and benzoyl derivatives and to test their antileishmanial activity in vitro and in vivo against L. i. chagasi. A screening assay using luciferase-expressing promastigotes was used to measure the growth inhibition of promastigotes, and an ELISA in situ was performed to evaluate the growth inhibition of amastigote. For the in vivo assay, thymol and eugenol derivatives were given IP to BALB/c mice at 100 mg/kg/day for 30 days. The thymol derivatives demonstrated the greater activity than the eugenol derivatives, and benzoyl- thymol was the best inhibitor (8.67 ± 0.28 μg/mL). All compounds demonstrated similar activity against amastigotes, and acetyl-thymol was more active than thymol and the positive control drug amphotericin B. Immunohistochemistry demonstrated the presence of Leishmania amastigote only in the spleen but not the liver of mice treated with acetyl-thymol. Thus, these synthesized derivatives demonstrated anti-leishmanial activity both in vitro and in vivo. These may constitute useful compounds to generate new agents for treatment of leishmaniasis. PMID:25281268

  5. Potential serotonergic agents for the treatment of schizophrenia.

    PubMed

    Garay, Ricardo P; Bourin, Michel; de Paillette, Evelyne; Samalin, Ludovic; Hameg, Ahcène; Llorca, Pierre-Michel

    2016-01-01

    For the last 30 years, drugs targeting serotonin receptors (5-HTR) have been intensively investigated in schizophrenia. New drugs targeting 5-HTRs are under development in patients with schizophrenia. In this review, the authors describe the recent clinical trials for schizophrenia with selective serotonergic agents and provide an opinion on how the investigated drugs can help to fulfil current treatment needs. Clinical trials were found in US and EU clinical trial registries and in the medical literature. Relevant 5-HTR antagonists active in animal models of schizophrenia were also analysed. Antipsychotics reduce positive symptoms of schizophrenia (delusions, hallucinations and disordered thought), but have undesirable side effects. Moreover, satisfactory treatment of negative symptoms (apathy, poverty of speech, lack of interest in social interactions) and cognitive dysfunction is currently not available. The selective 5-HT2CR full agonist vabicaserin showed antipsychotic efficacy with fewer side effects than olanzapine. Adjunctive pimavanserin (a selective 5-HT2AR inverse agonist) facilitated antipsychotic dose and side-effect reductions. Selective 5-HT3R antagonists (ondansetron, tropisetron and granisetron) showed positive results on negative symptoms and/or cognitive impairments in phase II trials. Adjunctive ondansetron has now entered a phase III trial for such indications. Finally, 5-HTA5R and 5-HT7R antagonists have shown procognitive actions in animal models of schizophrenia. These novel serotonergic drugs seem promising for improving the current treatment of schizophrenia.

  6. Cotinine: a potential new therapeutic agent against Alzheimer's disease.

    PubMed

    Echeverria, Valentina; Zeitlin, Ross

    2012-07-01

    Tobacco smoking has been correlated with a lower incidence of Alzheimer's disease (AD). This negative correlation has been attributed to nicotine's properties. However, the undesired side-effects of nicotine and the absence of clear evidence of positive effects of this drug on the cognitive abilities of AD patients have decreased the enthusiasm for its therapeutic use. In this review, we discuss evidence showing that cotinine, the main metabolite of nicotine, has many of the beneficial effects but none of the negative side-effects of its precursor. Cotinine has been shown to be neuroprotective, to improve memory in primates as well as to prevent memory loss, and to lower amyloid-beta (Aβ)) burden in AD mice. In AD, cotinine's positive effect on memory is associated with the inhibition of Aβ aggregation, the stimulation of pro-survival factors such as Akt, and the inhibition of pro-apoptotic factors such as glycogen synthase kinase 3 beta (GSK3β). Because stimulation of the α7 nicotinic acetylcholine receptors (α7nAChRs) positively modulates these factors and memory, the involvement of these receptors in cotinine's effects are discussed. Because of its beneficial effects on brain function, good safety profile, and nonaddictive properties, cotinine may represent a new therapeutic agent against AD.

  7. Calcium fructoborate--potential anti-inflammatory agent.

    PubMed

    Scorei, Romulus Ion; Rotaru, Petre

    2011-12-01

    Calcium fructoborate is a boron-based nutritional supplement. Its chemical structure is similar to one of the natural forms of boron such as bis-manitol, bis-sorbitol, bis-fructose, and bis-sucrose borate complexes found in edible plants. In vitro studies revealed that calcium fructoborate is a superoxide ion scavenger and anti-inflammatory agent. It may influence macrophage production of inflammatory mediators, can be beneficial for the suppression of cytokine production, and inhibits progression of endotoxin-associated diseases, as well as the boric acid and other boron sources. The mechanisms by which calcium fructoborate exerts its beneficial anti-inflammatory effects are not entirely clear, but some of its molecular biological in vitro activities are understood: inhibition of the superoxide within the cell; inhibition of the interleukin-1β, interleukin-6, and nitric oxide release in the culture media; and increase of the tumor necrosis factor-α production. Also, calcium fructoborate has no effects on lipopolysaccharide-induced cyclooxygenase-2 protein express. The studies on animals and humans with a dose range of 1-7 mg calcium fructoborate (0.025-0.175 mg elemental boron)/kg body weight/day exhibited a good anti-inflammatory activity, and it also seemed to have negligible adverse effect on humans.

  8. Influence of potentially remineralizing agents on bleached enamel microhardness.

    PubMed

    Borges, Alessandra Bühler; Samezima, Leticia Yumi; Fonseca, Léila Pereira; Yui, Karen Cristina Kazue; Borges, Alexandre Luiz Souto; Torres, Carlos Rocha Gomes

    2009-01-01

    This study investigated the effect of the addition of calcium and fluoride into a 35% hydrogen peroxide gel on enamel surface and subsurface microhardness. Twenty extracted human third molars were sectioned to obtain enamel fragments and they were divided into four groups (n = 20) according to the bleaching treatment. Group 1 received no bleaching procedure (control). Group 2 was treated with a 35% hydrogen peroxide gel (Total Bleach), Groups 3 and 4 were bleached with Total Bleach modified by the addition of sodium fluoride and calcium chloride, respectively. The microhardness of the enamel surface was assessed using a Vickers microdurometer immediately after the bleaching treatment. The specimens were sectioned in the central portion, polished and evaluated to determine the microhardness of the enamel subsurface to a depth of 125 microm, with an interval of 25 microm between measures. There were significant differences among the groups. In terms of surface microhardness, the bleached group exhibited the lowest means, and the calcium-modified bleached group exhibited the highest means. Regarding subsurface microhardness, there were no significant differences among the groups for the depth and interaction factors. The bleached group exhibited the lowest means, and the calcium-modified bleached group presented the highest means. It was concluded that the bleaching treatment with 35% hydrogen peroxide significantly reduced the surface and subsurface microhardness of the enamel, and the addition of fluoride and calcium in the bleaching agent increased the microhardness means of the bleached enamel.

  9. Neem components as potential agents for cancer prevention and treatment.

    PubMed

    Hao, Fang; Kumar, Sandeep; Yadav, Neelu; Chandra, Dhyan

    2014-08-01

    Azadirachta indica, also known as neem, is commonly found in many semi-tropical and tropical countries including India, Pakistan, and Bangladesh. The components extracted from neem plant have been used in traditional medicine for the cure of multiple diseases including cancer for centuries. The extracts of seeds, leaves, flowers, and fruits of neem have consistently shown chemopreventive and antitumor effects in different types of cancer. Azadirachtin and nimbolide are among the few bioactive components in neem that have been studied extensively, but research on a great number of additional bioactive components is warranted. The key anticancer effects of neem components on malignant cells include inhibition of cell proliferation, induction of cell death, suppression of cancer angiogenesis, restoration of cellular reduction/oxidation (redox) balance, and enhancement of the host immune responses against tumor cells. While the underlying mechanisms of these effects are mostly unclear, the suppression of NF-κB signaling pathway is, at least partially, involved in the anticancer functions of neem components. Importantly, the anti-proliferative and apoptosis-inducing effects of neem components are tumor selective as the effects on normal cells are significantly weaker. In addition, neem extracts sensitize cancer cells to immunotherapy and radiotherapy, and enhance the efficacy of certain cancer chemotherapeutic agents. This review summarizes the current updates on the anticancer effects of neem components and their possible impact on managing cancer incidence and treatment.

  10. A Nitric Oxide-Releasing Heparin Conjugate for Delivery of a Combined Antiplatelet/Anticoagulant Agent

    PubMed Central

    2015-01-01

    Heparin is a widely used anticoagulant due to its ability to inhibit key components in the coagulation cascade such as Factor Xa and thrombin (Factor IIa). Its potential to preferentially bind to antithrombin (ATIII) results in a conformational change and activation that leads to the prevention of fibrin formation from fibrinogen and ultimately obstructs a hemostatic plug from forming. Nitric oxide (NO) exhibits potent antiplatelet activity attributed to its capacity to increase the amount of cyclic guanosine monophosphate (cGMP) within platelets, which decreases the Ca2+ concentration required for platelet activation. Currently there is no single agent that combines the functions of both antiplatelet and anticoagulant (anti-Xa and anti-IIa) activities to effectively block both the extrinsic and the intrinsic coagulation pathways. The research reported herein demonstrates the ability to combine the physiological capabilities of both heparin and NO into one functional compound via use of a spermine derivative of heparin, thus enabling formation of a novel diazeniumdiolate (NONOate). The heparin–spermine NONOate has a half-life of 85 min at 25 °C (pH 7.4). The heparin backbone of the conjugate maintains its anticoagulant activity as demonstrated via an anti-Xa assay, providing an anticoagulant conversion of 3.6 μg/mL of the heparin–spermine–NONO conjugate being equivalent to 2.5 μg/mL (0.50 IU/mL) of underivatized heparin in terms of anti-Xa activity. Using standard platelet aggregometry, it is shown that the functionality of the NO release portion of the heparin conjugate prevents (nearly 100%) platelet aggregation in the presence of adenosine diphosphate (ADP, platelet agonist). PMID:24423090

  11. Fabrication of Highly Uniform Nanoparticles from Recombinant Silk-Elastinlike Protein Polymers for Therapeutic Agent Delivery

    PubMed Central

    Anumolu, Rajasekhar; Gustafson, Joshua A.; Magda, Jules J.; Cappello, Joseph; Ghandehari, Hamidreza; Pease, Leonard F.

    2011-01-01

    Here we generate silk-elastinlike protein (SELP) polymeric nanoparticles and demonstrate precise control over their dimensions using an electrospray differential mobility analyzer (ES-DMA). Electrospray produces droplets encompassing several polymer strands. Evaporation ensues, leading polymer strands to accumulate at the droplet interface forming a hollow nanoparticle. The resulting nanoparticle size distributions which govern particle yield, depend on buffer concentration to the −1/3 power, polymer concentration to the 1/3 power, and ratio of silk to elastin blocks. Three recombinantly tuned ratios of silk to elastin blocks, 8:16, 4:8, and 4:16, respectively named SELP-815K, SELP-47K, and SELP-415K, are employed with the latter ratio resulting in a thinner shell and larger diameter for the nanoparticles than the former. The DMA narrows the size distribution by electrostatically classifying the aerosolized nanoparticles. These highly uniform nanoparticles have variations of 1.2 nm and 1.4 nm for 24.0 nm and 36.0 nm particles, respectively. Transmission electron microscopy reveals the nanoparticles to be faceted, as a buckling instability releases compression energy arising from evaporation after the shell has formed by bending it. A thermodynamic equilibrium exists between compression and bending energies, where the facet length is 1/2 the particle diameter, in agreement with experiments. Rod-like particles also formed from polymer stabilized filaments when the viscous length exceeds the jet radius at higher solution viscosities. The unusual uniformity in composition and dimension indicates the potential of these nanoparticles to deliver bioactive and imaging agents. PMID:21696150

  12. Lactic acid bacteria: reviewing the potential of a promising delivery live vector for biomedical purposes.

    PubMed

    Cano-Garrido, Olivia; Seras-Franzoso, Joaquin; Garcia-Fruitós, Elena

    2015-09-16

    Lactic acid bacteria (LAB) have a long history of safe exploitation by humans, being used for centuries in food production and preservation and as probiotic agents to promote human health. Interestingly, some species of these Gram-positive bacteria, which are generally recognized as safe organisms by the US Food and Drug Administration (FDA), are able to survive through the gastrointestinal tract (GIT), being capable to reach and colonize the intestine, where they play an important role. Besides, during the last decades, an important effort has been done for the development of tools to use LAB as microbial cell factories for the production of proteins of interest. Given the need to develop effective strategies for the delivery of prophylactic and therapeutic molecules, LAB have appeared as an appealing option for the oral, intranasal and vaginal delivery of such molecules. So far, these genetically modified organisms have been successfully used as vehicles for delivering functional proteins to mucosal tissues in the treatment of many different pathologies including GIT related pathologies, diabetes, cancer and viral infections, among others. Interestingly, the administration of such microorganisms would suppose a significant decrease in the production cost of the treatments agents since being live organisms, such vectors would be able to autonomously amplify and produce and deliver the protein of interest. In this context, this review aims to provide an overview of the use of LAB engineered as a promising alternative as well as a safety delivery platform of recombinant proteins for the treatment of a wide range of diseases.

  13. THE SYNTHESIS OF POTENTIAL ANTI-RADIATION AGENTS

    DTIC Science & Technology

    potentially capable of carrying it into nu leic acids, was completed. Since replacement of the sulfur of cysteamine with selenium does not destroy...products (2-aminoselenazolines and 2-selenoethylguanidines) were prepared. The bis Bunte salt of bis(2-mercaptoethyl)amine the doublearmed analog of cysteamine was synthesized. (Author)

  14. From naturally-occurring neurotoxic agents to CNS shuttles for drug delivery.

    PubMed

    Soddu, Elena; Rassu, Giovanna; Giunchedi, Paolo; Sarmento, Bruno; Gavini, Elisabetta

    2015-07-10

    Central nervous system (CNS) diseases are hard to diagnose and therapeutically target due to the blood brain barrier (BBB), which prevents most drugs from reaching their sites of action within the CNS. Brain drug delivery systems were conceived to bypass the BBB and were derived from anatomical and functional analysis of the BBB; this analysis led researchers to take advantage of brain endothelial membrane physiology to allow drug access across the BBB. Both receptors and carriers can be used to transport endogenous and exogenous substances into the CNS. Combining a drug with substances that take advantage of these internalization mechanisms is a widely exploited strategy for drug delivery because it is an indirect method that overcomes the BBB in a non-invasive way and is therefore less dangerous and costly than invasive methods. Neurotoxins, among other naturally-occurring substances, may be used as drug carriers to specifically target the CNS. This review covers the current delivery systems that take advantage of the non-toxic components of neurotoxins to overcome the BBB and reach the CNS. We hope to give insights to researchers toward developing new delivery systems that exploit the positive features of substances usually regarded as natural hazards.

  15. Cellular and vascular effects of the photodynamic agent temocene are modulated by the delivery vehicle

    PubMed Central

    García-Díaz, María; Kawakubo, Masayoshi; Mroz, Pawel; Sagristà, M. Lluïsa; Mora, Margarita; Nonell, Santi; Hamblin, Michael R.

    2012-01-01

    The effects of the drug delivery system on the PDT activity, localization, and tumor accumulation of the novel photosensitizer temocene (the porphycene analogue of temoporfin or m-tetrahydroxyphenyl chlorin) were investigated against the P815 tumor, both in vitro and in DBA/2 tumor bearing mice. Temocene was administered either free (dissolved in PEG400/EtOH mixture), or encapsulated in Cremophor EL micelles or in DPPC/DMPG liposomes, chosen as model delivery vehicles. The maximum cell accumulation and photodynamic activity in vitro was achieved with the free photosensitizer, while temocene in Cremophor micelles hardly entered the cells. Notwithstanding, the micellar formulation showed the best in vivo response when used in a vascular regimen (short drug light interval), whereas liposomes were found to be an efficient drug delivery system for a tumor cell targeting strategy (long drug-light interval). PEG/EtOH formulation was discarded for further in vivo experiments as it provoked lethal toxic effects caused by photosensitizer aggregation. These results demonstrate that drug delivery systems modulate the vascular and cellular outcomes of photodynamic treatments with temocene. PMID:22841794

  16. Cellular and vascular effects of the photodynamic agent temocene are modulated by the delivery vehicle.

    PubMed

    García-Díaz, María; Kawakubo, Masayoshi; Mroz, Pawel; Sagristà, M Lluïsa; Mora, Margarita; Nonell, Santi; Hamblin, Michael R

    2012-09-10

    The effects of the drug delivery system on the PDT activity, localization, and tumor accumulation of the novel photosensitizer temocene (the porphycene analogue of temoporfin or m-tetrahydroxyphenyl chlorin) were investigated against the P815 tumor, both in vitro and in DBA/2 tumor bearing mice. Temocene was administered either free (dissolved in PEG(400)/EtOH mixture), or encapsulated in Cremophor EL micelles or in DPPC/DMPG liposomes, chosen as model delivery vehicles. The maximum cell accumulation and photodynamic activity in vitro was achieved with the free photosensitizer, while temocene in Cremophor micelles hardly entered the cells. Notwithstanding, the micellar formulation showed the best in vivo response when used in a vascular regimen (short drug light interval), whereas liposomes were found to be an efficient drug delivery system for a tumor cell targeting strategy (long drug-light interval). PEG/EtOH formulation was discarded for further in vivo experiments as it provoked lethal toxic effects caused by photosensitizer aggregation. These results demonstrate that drug delivery systems modulate the vascular and cellular outcomes of photodynamic treatments with temocene. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. Repositioning of chlorambucil as a potential anti-schistosomal agent.

    PubMed

    Eissa, Maha M; Mossallam, Shereen F; Amer, Eglal I; Younis, Layla K; Rashed, Hoda A

    2017-02-01

    As parasites and cancer cells share many lifestyle and behavioral resemblances, repositioning of anti-cancerous agents as anti-parasitic is quite trendy, especially those sharing the same therapeutic targets. Therefore, the current study investigated the in vitro efficacy of ascending concentrations of chlorambucil (0.5-20μg/ml) against adult Schistosoma mansoni worms, over 72h. Additionally, its in vivo effects against the different developmental stages of the worm were assessed, after an oral dose of 2.5mg/kg/day for five successive days, through evaluating the worm load reduction and worms' morphological alterations and oogram changes. In addition to tissue egg count, a histopathological study of the liver was conducted. In vitro, chlorambucil demonstrated noticeable anti-schistosomal effects in the form of progressive reductions of the worms' viability in a dose dependent manner. Complete worm death was achieved at 72h incubation with 5μg/ml drug concentration. In vivo, chlorambucil induced a significant reduction in the total worm load against all developmental stages. Its highest impact was evident against the juvenile stage, where it induced 75.8% total worm load reduction, and 89.2% and 86.7% intestinal and hepatic egg counts reduction, respectively, along with ogram alterations. Besides, it induced significant shortening of both male and female worms and promoted an amelioration of hepatic histopathology. Results show that chlorambucil possesses favorable in vitro and in vivo anti-schistosomal activity. The highest in vivo efficacy was against the juvenile stage of S. mansoni, significantly superior to praziquantel, with extended potency to the adult stage. Further studies are recommended for chlorambucil target verification and to enhance its therapeutic efficacy. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. The toxicology of bioregulators as potential agents of bioterrorism.

    PubMed

    Bokan, Slavko

    2005-06-01

    Bioregulators or modulators are biochemical compounds such as peptides, that occur naturally in organisms. Advances in biotechnology create the potential for the misuse of peptide bioregulators in offensive biological weapons programmes. Bioregulators are a new class of weapons that can damage the nervous system, alter mood, trigger psychological changes and kill. Over the last twenty years, neuroscience has produced an explosion of knowledge about receptor systems in the nerve cells that are of critical importance in receiving chemical transmitter substances released by other nerve cells. Bioregulators are closely related to substances normally found in the body that regulates normal biological processes. The potential military or terrorist use of bioregulators is similar to that of toxins. Together with increased research into toxins, the bioregulators have also been studied and synthesized. This paper presents a review of bioregulators that could be used in terrorist or other hostile activities.

  19. Strategies for ocular siRNA delivery: Potential and limitations of non-viral nanocarriers.

    PubMed

    Thakur, Ajit; Fitzpatrick, Scott; Zaman, Abeyat; Kugathasan, Kapilan; Muirhead, Ben; Hortelano, Gonzalo; Sheardown, Heather

    2012-06-11

    Controlling gene expression via small interfering RNA (siRNA) has opened the doors to a plethora of therapeutic possibilities, with many currently in the pipelines of drug development for various ocular diseases. Despite the potential of siRNA technologies, barriers to intracellular delivery significantly limit their clinical efficacy. However, recent progress in the field of drug delivery strongly suggests that targeted manipulation of gene expression via siRNA delivered through nanocarriers can have an enormous impact on improving therapeutic outcomes for ophthalmic applications. Particularly, synthetic nanocarriers have demonstrated their suitability as a customizable multifunctional platform for the targeted intracellular delivery of siRNA and other hydrophilic and hydrophobic drugs in ocular applications. We predict that synthetic nanocarriers will simultaneously increase drug bioavailability, while reducing side effects and the need for repeated intraocular injections. This review will discuss the recent advances in ocular siRNA delivery via non-viral nanocarriers and the potential and limitations of various strategies for the development of a 'universal' siRNA delivery system for clinical applications.

  20. Strategies for ocular siRNA delivery: Potential and limitations of non-viral nanocarriers

    PubMed Central

    2012-01-01

    Controlling gene expression via small interfering RNA (siRNA) has opened the doors to a plethora of therapeutic possibilities, with many currently in the pipelines of drug development for various ocular diseases. Despite the potential of siRNA technologies, barriers to intracellular delivery significantly limit their clinical efficacy. However, recent progress in the field of drug delivery strongly suggests that targeted manipulation of gene expression via siRNA delivered through nanocarriers can have an enormous impact on improving therapeutic outcomes for ophthalmic applications. Particularly, synthetic nanocarriers have demonstrated their suitability as a customizable multifunctional platform for the targeted intracellular delivery of siRNA and other hydrophilic and hydrophobic drugs in ocular applications. We predict that synthetic nanocarriers will simultaneously increase drug bioavailability, while reducing side effects and the need for repeated intraocular injections. This review will discuss the recent advances in ocular siRNA delivery via non-viral nanocarriers and the potential and limitations of various strategies for the development of a ‘universal’ siRNA delivery system for clinical applications. PMID:22686441

  1. Synthesis of genistein 2,3-anhydroglycoconjugates -- potential antiproliferative agents.

    PubMed

    Goj, Katarzyna; Rusin, Aleksandra; Szeja, Wiesław; Kitel, Radosław; Komor, Roman; Grynkiewicz, Grzegorz

    2012-01-01

    The title compounds, variously protected 2.3-anhydrosugars linked with genistein through an alkyl chain, were synthesized in a sequence of reactions. First step involved Ferrier rearragement of 3,4-di-O-acetyl-L-rhamnal with 3-bromopropanol to obtain 2,3-unsaturated bromoalkylglycosides. The next step was epoxidation with m-CPBA and finally these compounds were connected with genistein in reaction of 7-O-genistein tetra-butylamonium salt with 2,3-anhydro bromoalkylglycosides. Obtained glycoconjugates differ in orientation of an oxirane ring and the protecting group in a sugar moiety. All compounds were tested in vitro for antiproliferative potential in cancer cells.

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

    PubMed

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

    2015-07-21

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

  3. Handheld delivery system for modified boron-type fire extinguishment agent

    NASA Astrophysics Data System (ADS)

    Lee, Michael E.; Tapscott, Robert E.

    1993-11-01

    A handheld, portable extinguisher was developed for Boralon, a modified Boron-type Class D fire extinguishing agent. The development of this unit progressed through the design, prototype, and final product stages. Two prototypes were designed as valved, stored-pressure types using Boralon compatible materials in critical areas exposed to the agent. The units were tested at an operating pressure of 200 lbf/sq in and an agent capacity of 2 to 3 gallons to determine the optimum application rate, throw range and throw pattern. The most favorable unit was tested for reliability. The information obtained in the prototype testing was developed further into a final design. This design specified a stored-pressure type that was sealed with a frangible plug or splined rupture disk and was activated by depressing the handle and removing the seal. Further requirements of a fill ratio of 75 percent agent to 25 percent pressure head at 200 lbf/sq in and an agent fill capacity of at least 2 gallons were also specified. Two manufactured units were found that met the criteria. An extinguisher with a frangible plug seal was successfully tested against 30- and 50-pound magnesium fires. Both the frangible plug and splined rupture disk designs satisfy the final design requirements of the handheld Boralon extinguisher. Both types are recommended for use in the Draft Military Specification for this unit.

  4. Potential Antiviral Agents from Marine Fungi: An Overview.

    PubMed

    Moghadamtousi, Soheil Zorofchian; Nikzad, Sonia; Kadir, Habsah Abdul; Abubakar, Sazaly; Zandi, Keivan

    2015-07-22

    Biodiversity of the marine world is only partially subjected to detailed scientific scrutiny in comparison to terrestrial life. Life in the marine world depends heavily on marine fungi scavenging the oceans of lifeless plants and animals and entering them into the nutrient cycle by. Approximately 150 to 200 new compounds, including alkaloids, sesquiterpenes, polyketides, and aromatic compounds, are identified from marine fungi annually. In recent years, numerous investigations demonstrated the tremendous potential of marine fungi as a promising source to develop new antivirals against different important viruses, including herpes simplex viruses, the human immunodeficiency virus, and the influenza virus. Various genera of marine fungi such as Aspergillus, Penicillium, Cladosporium, and Fusarium were subjected to compound isolation and antiviral studies, which led to an illustration of the strong antiviral activity of a variety of marine fungi-derived compounds. The present review strives to summarize all available knowledge on active compounds isolated from marine fungi with antiviral activity.

  5. Potential Antiosteoporotic Agents from Plants: A Comprehensive Review

    PubMed Central

    Jia, Min; Nie, Yan; Cao, Da-Peng; Xue, Yun-Yun; Wang, Jie-Si; Zhao, Lu; Rahman, Khalid; Zhang, Qiao-Yan; Qin, Lu-Ping

    2012-01-01

    Osteoporosis is a major health hazard and is a disease of old age; it is a silent epidemic affecting more than 200 million people worldwide in recent years. Based on a large number of chemical and pharmacological research many plants and their compounds have been shown to possess antiosteoporosis activity. This paper reviews the medicinal plants displaying antiosteoporosis properties including their origin, active constituents, and pharmacological data. The plants reported here are the ones which are commonly used in traditional medical systems and have demonstrated clinical effectiveness against osteoporosis. Although many plants have the potential to prevent and treat osteoporosis, so far, only a fraction of these plants have been thoroughly investigated for their physiological and pharmacological properties including their mechanism of action. An attempt should be made to highlight plant species with possible antiosteoporosis properties and they should be investigated further to help with future drug development for treating this disease. PMID:23365596

  6. Nutraceuticals as potential therapeutic agents for colon cancer: a review.

    PubMed

    Kuppusamy, Palaniselvam; Yusoff, Mashitah M; Maniam, Gaanty Pragas; Ichwan, Solachuddin Jauhari Arief; Soundharrajan, Ilavenil; Govindan, Natanamurugaraj

    2014-06-01

    Colon cancer is a world-wide health problem and the second-most dangerous type of cancer, affecting both men and women. The modern diet and lifestyles, with high meat consumption and excessive alcohol use, along with limited physical activity has led to an increasing mortality rate for colon cancer worldwide. As a result, there is a need to develop novel and environmentally benign drug therapies for colon cancer. Currently, nutraceuticals play an increasingly important role in the treatment of various chronic diseases such as colon cancer, diabetes and Alzheimer׳s disease. Nutraceuticals are derived from various natural sources such as medicinal plants, marine organisms, vegetables and fruits. Nutraceuticals have shown the potential to reduce the risk of colon cancer and slow its progression. These dietary substances target different molecular aspects of colon cancer development. Accordingly, this review briefly discusses the medicinal importance of nutraceuticals and their ability to reduce the risk of colorectal carcinogenesis.

  7. Melatonin as a Potential Agent in the Treatment of Sarcopenia

    PubMed Central

    Coto-Montes, Ana; Boga, Jose A.; Tan, Dun X.; Reiter, Russel J.

    2016-01-01

    Considering the increased speed at which the world population is aging, sarcopenia could become an epidemic in this century. This condition currently has no means of prevention or treatment. Melatonin is a highly effective and ubiquitously acting antioxidant and free radical scavenger that is normally produced in all organisms. This molecule has been implicated in a huge number of biological processes, from anticonvulsant properties in children to protective effects on the lung in chronic obstructive pulmonary disease. In this review, we summarize the data which suggest that melatonin may be beneficial in attenuating, reducing or preventing each of the symptoms that characterize sarcopenia. The findings are not limited to sarcopenia, but also apply to osteoporosis-related sarcopenia and to age-related neuromuscular junction dysfunction. Since melatonin has a high safety profile and is drastically reduced in advanced age, its potential utility in the treatment of sarcopenic patients and related dysfunctions should be considered. PMID:27783055

  8. Nutraceuticals as potential therapeutic agents for colon cancer: a review

    PubMed Central

    Kuppusamy, Palaniselvam; Yusoff, Mashitah M.; Maniam, Gaanty Pragas; Ichwan, Solachuddin Jauhari Arief; Soundharrajan, Ilavenil; Govindan, Natanamurugaraj

    2014-01-01

    Colon cancer is a world-wide health problem and the second-most dangerous type of cancer, affecting both men and women. The modern diet and lifestyles, with high meat consumption and excessive alcohol use, along with limited physical activity has led to an increasing mortality rate for colon cancer worldwide. As a result, there is a need to develop novel and environmentally benign drug therapies for colon cancer. Currently, nutraceuticals play an increasingly important role in the treatment of various chronic diseases such as colon cancer, diabetes and Alzheimer׳s disease. Nutraceuticals are derived from various natural sources such as medicinal plants, marine organisms, vegetables and fruits. Nutraceuticals have shown the potential to reduce the risk of colon cancer and slow its progression. These dietary substances target different molecular aspects of colon cancer development. Accordingly, this review briefly discusses the medicinal importance of nutraceuticals and their ability to reduce the risk of colorectal carcinogenesis. PMID:26579381

  9. Marine fish-derived bioactive peptides as potential antihypertensive agents.

    PubMed

    Kim, Se-Kwon; Ngo, Dai-Hung; Vo, Thanh-Sang

    2012-01-01

    Hypertension is the most widespread risk factor for many serious cardiovascular diseases. Angiotensin-converting enzyme (ACE) plays a crucial role in cardiovascular physiological regulation by converting angiotensin I to a potent vasoconstrictor, angiotensin II. Hence, the inhibition of ACE is a key target for antihypertensive activity. Recently, potent antihypertensive peptides have been purified widely by enzymatic hydrolysis of muscle protein, skin collagen, and gelatin of many different kinds of marine fishes. Marine fish-derived bioactive peptides can be developed as antihypertensive components in functional foods or nutraceuticals. This contribution presents an overview of the ACE inhibitory peptides derived from marine fishes and discusses their future prospects to be used as potential drug candidates for preventing and treating high blood pressure. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Pyrimidine derivatives as potential agents acting on central nervous system.

    PubMed

    Kumar, Sanjiv; Deep, Aakash; Narasimhan, Balasubramanian

    2015-01-01

    Pyrimidine and its derivatives are present in many of the bioactive aromatic compounds that are of wide interest because of their diverse biological and clinical applications. The utility of pyrimidines as synthon for various biologically active compounds has given impetus to these studies. The review article aims to review the work reported on pharmacological activities of central nervous system (CNS) such as anticonvulsant and antidepressant, which created interest among researchers to synthesize variety of pyrimidine and their derivatives. The present study shows, objective of the work can be summarized as pyrimidine derivative constitute an important class of compounds for new drug development. These observations have been given novel idea for the development of new pyrimidine derivative that possess varied biological activities. This article aims to review the recent works on pyrimidine moiety together with the biological potential during the past year.

  11. Melatonin as a Potential Agent in the Treatment of Sarcopenia.

    PubMed

    Coto-Montes, Ana; Boga, Jose A; Tan, Dun X; Reiter, Russel J

    2016-10-24

    Considering the increased speed at which the world population is aging, sarcopenia could become an epidemic in this century. This condition currently has no means of prevention or treatment. Melatonin is a highly effective and ubiquitously acting antioxidant and free radical scavenger that is normally produced in all organisms. This molecule has been implicated in a huge number of biological processes, from anticonvulsant properties in children to protective effects on the lung in chronic obstructive pulmonary disease. In this review, we summarize the data which suggest that melatonin may be beneficial in attenuating, reducing or preventing each of the symptoms that characterize sarcopenia. The findings are not limited to sarcopenia, but also apply to osteoporosis-related sarcopenia and to age-related neuromuscular junction dysfunction. Since melatonin has a high safety profile and is drastically reduced in advanced age, its potential utility in the treatment of sarcopenic patients and related dysfunctions should be considered.

  12. Potential Antiviral Agents from Marine Fungi: An Overview

    PubMed Central

    Zorofchian Moghadamtousi, Soheil; Nikzad, Sonia; Abdul Kadir, Habsah; Abubakar, Sazaly; Zandi, Keivan

    2015-01-01

    Biodiversity of the marine world is only partially subjected to detailed scientific scrutiny in comparison to terrestrial life. Life in the marine world depends heavily on marine fungi scavenging the oceans of lifeless plants and animals and entering them into the nutrient cycle by. Approximately 150 to 200 new compounds, including alkaloids, sesquiterpenes, polyketides, and aromatic compounds, are identified from marine fungi annually. In recent years, numerous investigations demonstrated the tremendous potential of marine fungi as a promising source to develop new antivirals against different important viruses, including herpes simplex viruses, the human immunodeficiency virus, and the influenza virus. Various genera of marine fungi such as Aspergillus, Penicillium, Cladosporium, and Fusarium were subjected to compound isolation and antiviral studies, which led to an illustration of the strong antiviral activity of a variety of marine fungi-derived compounds. The present review strives to summarize all available knowledge on active compounds isolated from marine fungi with antiviral activity. PMID:26204947

  13. A review of ceramide analogs as potential anticancer agents

    PubMed Central

    Liu, Jiawang; Beckman, Barbara S.; Foroozesh, Maryam

    2014-01-01

    Summary Ceramide serves as a central mediator in sphingolipid metabolism and signaling pathways, regulating many fundamental cellular responses. It is referred to as a “tumor suppressor lipid”, since it powerfully potentiates signaling events which drive apoptosis, cell cycle arrest, and autophagic responses. In the typical cancer cell, ceramide levels and signaling are usually suppressed by over-expression of ceramide-metabolizing enzymes or down-regulation of ceramide-generating enzymes. However, chemotherapeutic drugs as well as radiotherapy increase intracellular ceramide levels while exogenously treating cancer cells with short-chain ceramides leads to anti-cancer effects. All evidence currently points to the fact that the up-regulation of ceramide level is a promising anti-cancer target. In this review, we exhibited a full scroll of anti-cancer ceramide analogs as down-stream receptor agonists and ceramide metabolizing enzyme inhibitors. PMID:23919551

  14. Morphine as a Potential Oxidative Stress-Causing Agent.

    PubMed

    Skrabalova, Jitka; Drastichova, Zdenka; Novotny, Jiri

    2013-11-01

    Morphine exhibits important pharmacological effects for which it has been used in medical practice for quite a long time. However, it has a high addictive potential and can be abused. Long-term use of this drug can be connected with some pathological consequences including neurotoxicity and neuronal dysfunction, hepatotoxicity, kidney dysfunction, oxidative stress and apoptosis. Therefore, most studies examining the impact of morphine have been aimed at determining the effects induced by chronic morphine exposure in the brain, liver, cardiovascular system and macrophages. It appears that different tissues may respond to morphine diversely and are distinctly susceptible to oxidative stress and subsequent oxidative damage of biomolecules. Importantly, production of reactive oxygen/nitrogen species induced by morphine, which have been observed under different experimental conditions, can contribute to some pathological processes, degenerative diseases and organ dysfunctions occurring in morphine abusers or morphine-treated patients. This review attempts to provide insights into the possible relationship between morphine actions and oxidative stress.

  15. In vitro and in vivo iontophoretic transdermal delivery of an anti-parkinsonian agent.

    PubMed

    Vemulapalli, V; Yang, Y; Siddoju, S; Conjeevaram, R; Teunissen, H; Myers, T; Banga, A K

    2011-11-25

    To objective of this work was to study the feasibility of iontophoretic delivery of SLV 318 (7-(4-benzyl-1-piperazinyl)-2(3H)-benzoxazolone methanesulfonate) across hairless rat skin in vitro and in vivo. The effect of counter-ions and temperature were investigated for optimizing SLV 318 solubility. The effect of electrode efficiency and total current applied on the delivery of SLV 318 were studied using Franz diffusion cells and samples were analyzed using HPLC. Delivery increased with increasing concentration. For current-time combinations, electrode had to be replaced every 9h. Passive, iontophoretic (0.1 mA/cm(2) for 1h) and intravenous studies were performed in vivo. Blood samples collected were analyzed using LC-MS/MS. SLV 318 had higher solubility with NaCl (75 mM) as a counter-ion at 25°C than with other counter-ions tested. In vivo iontophoresis significantly enhanced the permeation and also reduced its lag time (P<0.05). The C(max) of SLV 318 during 1h iontophoresis was 6.56 ± 0.68 ng/mL at 1.31 ± 0.29 h (T(max)) as compared to 2.96 ± 0.29 ng/mL at 25.32 ± 0.67 h (T(max)) by 24h passive permeation. The in vitro and in vivo data has shown the feasibility to enhance delivery of SLV 318 by iontophoresis.

  16. Co-delivery of siRNA and therapeutic agents using nanocarriers to overcome cancer resistance.

    PubMed

    Creixell, Mar; Peppas, Nicholas A

    2012-08-01

    There are two main mechanisms by which cells become multidrug resistant (MDR): by increasing drug efflux pumps on the cell membrane and by increasing anti-apoptotic pathways. The use of nanotechnology to develop nanodelivery systems has allowed researchers to overcome limitations of antineoplastic drugs by increasing the solubility of the drug and decreasing the toxicity to healthy tissues. By encapsulating drugs into nanoparticles that bypass the efflux pumps, drug efflux is reduced, hence increasing the intracellular concentration of the drug. siRNA has the ability to disrupt cellular pathways by knocking down genes, opening the door to down regulating anti-apoptotic pathways. The use of nanocarriers to deliver siRNA, prevents both renal clearance and RNase degradation by protecting siRNA chains, increasing their half life in blood. It has been suggested that co-delivering drugs and siRNA together in the same delivery system would be more effective in overcoming resistance of cancer cells than co-treatment of cancer cells with delivery systems carrying either siRNA or drugs. In this study we discuss the progress of nanoscale co-delivery systems in overcoming multidrug cancer resistance.

  17. The potentials of nanotechnology-based drug delivery system for treatment of ovarian cancer.

    PubMed

    Gidwani, Bina; Vyas, Amber

    2015-01-01

    Ovarian cancer is one of the leading causes for death of women. Every year the percentage of mortality rate is increasing day by day. Various chemotherapeutic agents are used to increase the survival rate of patients with ovarian cancer, but the available conventional dosage forms/marketed preparations are associated with several limitations. The use of nanotechnology in drug delivery contributes to their small size (10-100 nm), which improves the circulation and enables superior accumulation of therapeutic drugs at the tumor sites. In future, the use of nanotechnology will enable passive targeting and further improvements can be made using targeting moieties.

  18. Natural products as a source of potential cancer chemotherapeutic and chemopreventive agents.

    PubMed

    Cassady, J M; Baird, W M; Chang, C J

    1990-01-01

    Recent advances in the chemistry of novel bioactive natural products are reported. This research is directed to the exploration of plants with confirmed activity in bioassays designed to detect potential cancer chemotherapeutic and chemopreventive agents. Structural work and chemical studies are reported for several cytotoxic agents from the plants Annona densicoma, Annona reticulata, Claopodium crispifolium, Polytrichum obioense, and Psorospermum febrifugum. Studies are also reported based on development of a mammalian cell culture benzo[a]pyrene metabolism assay for the detection of potential anticarcinogenic agents from natural products. In this study a number of isoflavonoids and flavonoids with antimutagenic activity have been discovered.

  19. Aminosugar derivatives as potential anti-human immunodeficiency virus agents.

    PubMed Central

    Karpas, A; Fleet, G W; Dwek, R A; Petursson, S; Namgoong, S K; Ramsden, N G; Jacob, G S; Rademacher, T W

    1988-01-01

    Recent data suggest that aminosugar derivatives which inhibit glycoprotein processing have potential anti-human immunodeficiency virus (HIV) activity. These inhibitory effects may be due to disruption of cell fusion and subsequent cell-cell transmission of the acquired immunodeficiency syndrome (AIDS) virus. Free virus particles able to bind CD4-positive cells are still produced in the presence of these compounds with only partial reduction of infectivity. We now report a method to score in parallel both the degree of antiviral activity and the effect on cell division of aminosugar derivatives. We find that (i) the compounds 1,4-dideoxy-1,4-imino-L-arabinitol and N-(5-carboxymethyl-1-pentyl)-1,5-imino-L-fucitol partially inhibit the cytopathic effect (giant cell formation, etc.) of HIV and yield of infectious virus; (ii) the compounds N-methyldeoxynojirimycin and N-ethyldeoxynojirimycin reduce the yield of infectious HIV by an order of four and three logarithms, respectively; and (iii) one compound, N-butyldeoxynojirimycin, of the 47 compounds previously screened reduces infectious viral particles by a logarithmic order greater than five at noncytotoxic concentrations. In addition, long-term growth of infected cells in the presence of N-butyldeoxynojirimycin gradually decreases the proportion of infected cells, leading to eventual elimination of HIV from culture. This result suggests that replication is associated with cytolysis. The ability to break the cycle of replication and reinfection has important implications in the chemotherapy of AIDS. PMID:3264071

  20. Remineralizing potential of various agents on dental erosion

    PubMed Central

    Somani, Rani; Jaidka, Shipra; Singh, Deepti Jawa; Arora, Vanika

    2014-01-01

    Aim The purpose of this study is to compare the effect of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP, Tooth Mousse) containing and casein phosphopeptide-amorphous calcium phosphate with fluoride (CPP-ACPF, Tooth Mousse Plus) containing pastes on dental erosion. Materials and methods Thirty permanent non-carious premolars indicated for orthodontic extraction were included in this study and were sectioned in mesiodistal direction vertically. After immersion in the carbonated drink for 14 min, samples were treated with various remineralizing pastes which were CPP-ACP containing paste (Tooth Mousse) and CPP-ACPF containing paste (Tooth Mousse Plus) according to the manufacturer's instructions. Vickers Microhardness was recorded at baseline, after exposure to erosive drink and after treatment with remineralizing pastes. Data obtained was statistically analysed using Student t-test with a level of significance set at p < 0.05. Results CPP-ACP (Tooth Mousse) and CPP-ACP with fluoride (Tooth Mousse Plus) resulted in 30.52% and 38.98% increase in post-erosion microhardness values respectively. The remineralizing potential of CPP-ACP with fluoride containing paste (Tooth Mousse Plus) was significantly better than that of CPP-ACP containing paste (Tooth Mousse) (p < 0.05). Conclusion Casein phosphopeptide-amorphous calcium phosphate with fluoride (CPP-ACPF, Tooth Mousse Plus) can be recommended to be used in preventing erosive tooth wear from acidic beverages. PMID:25737926

  1. Investigation of Stilbenoids as Potential Therapeutic Agents for Rotavirus Gastroenteritis.

    PubMed

    Ball, Judith M; Medina-Bolivar, Fabricio; Defrates, Katelyn; Hambleton, Emily; Hurlburt, Megan E; Fang, Lingling; Yang, Tianhong; Nopo-Olazabal, Luis; Atwill, Richard L; Ghai, Pooja; Parr, Rebecca D

    2015-01-01

    Rotavirus (RV) infections cause severe diarrhea in infants and young children worldwide. Vaccines are available but cost prohibitive for many countries and only reduce severe symptoms. Vaccinated infants continue to shed infectious particles, and studies show decreased efficacy of the RV vaccines in tropical and subtropical countries where they are needed most. Continuing surveillance for new RV strains, assessment of vaccine efficacy, and development of cost effective antiviral drugs remain an important aspect of RV studies. This study was to determine the efficacy of antioxidant and anti-inflammatory stilbenoids to inhibit RV replication. Peanut (A. hypogaea) hairy root cultures were induced to produce stilbenoids, which were purified by high performance countercurrent chromatography (HPCCC) and analyzed by HPLC. HT29.f8 cells were infected with RV in the presence stilbenoids. Cell viability counts showed no cytotoxic effects on HT29.f8 cells. Viral infectivity titers were calculated and comparatively assessed to determine the effects of stilbenoid treatments. Two stilbenoids, trans-arachidin-1 and trans-arachidin-3, show a significant decrease in RV infectivity titers. Western blot analyses performed on the infected cell lysates complemented the infectivity titrations and indicated a significant decrease in viral replication. These studies show the therapeutic potential of the stilbenoids against RV replication.

  2. Potential New Agents for the Management of Hyperkalemia.

    PubMed

    Packham, David K; Kosiborod, Mikhail

    2016-02-01

    Hyperkalemia is a common electrolyte disturbance with multiple potential etiologies. It is usually observed in the setting of reduced renal function. Mild to moderate hyperkalemia is usually asymptomatic, but is associated with poor prognosis. When severe, hyperkalemia may cause serious acute cardiac arrhythmias and conduction abnormalities, and may result in sudden death. The rising prevalence of conditions associated with hyperkalemia (heart failure, chronic kidney disease, and diabetes) and broad use of renin-angiotensin-aldosterone system (RAAS) inhibitors and mineralocorticoid receptor antagonists (MRAs), which improve patient outcomes but increase the risk of hyperkalemia, have led to a significant rise in hyperkalemia-related hospitalizations and deaths. Current non-invasive therapies for hyperkalemia either do not remove excess potassium or have poor efficacy and tolerability. There is a clear need for safer, more effective potassium-lowering therapies suitable for both acute and chronic settings. Patiromer sorbitex calcium and sodium zirconium cyclosilicate (ZS-9) are two new potassium-lowering compounds currently in development. Although they have not yet been approved by the US FDA, both have demonstrated efficacy and safety in recent trials. Patiromer sorbitex calcium is a polymer resin and sorbitol complex that binds potassium in exchange for calcium; ZS-9, a non-absorbed, highly selective inorganic cation exchanger, traps potassium in exchange for sodium and hydrogen. This review discusses the merits of both novel drugs and how they may help optimize the future management of patients with hyperkalemia.

  3. Potential dermal wound healing agent in Blechnum orientale Linn

    PubMed Central

    2011-01-01

    Background Blechnum orientale Linn. (Blechnaceae) is used ethnomedicinally to treat wounds, boils, blisters or abscesses and sores, stomach pain and urinary bladder complaints. The aim of the study was to validate the ethnotherapeutic claim and to evaluate the effects of B. orientale water extract on wound healing activity. Methods Water extract of B. orientale was used. Excision wound healing activity was examined on Sprague-Dawley rats, dressed with 1% and 2% of the water extract. Control groups were dressed with the base cream (vehicle group, negative control) and 10% povidone-iodine (positive control) respectively. Healing was assessed based on contraction of wound size, mean epithelisation time, hydroxyproline content and histopathological examinations. Statistical analyses were performed using one way ANOVA followed by Tukey HSD test. Results Wound healing study revealed significant reduction in wound size and mean epithelisation time, and higher collagen synthesis in the 2% extract-treated group compared to the vehicle group. These findings were supported by histolopathological examinations of healed wound sections which showed greater tissue regeneration, more fibroblasts and angiogenesis in the 2% extract-treated group. Conclusions The ethnotherapeutic use of this fern is validated. The water extract of B. orientale is a potential candidate for the treatment of dermal wounds. Synergistic effects of both strong antioxidant and antibacterial activities in the extract are deduced to have accelerated the wound repair at the proliferative phase of the healing process. PMID:21835039

  4. Curcumin: a potential neuroprotective agent in Parkinson's disease.

    PubMed

    Mythri, R B; Bharath, M M Srinivas

    2012-01-01

    Parkinson's disease (PD) is an age-associated neurodegenerative disease clinically characterized as a movement disorder. The motor symptoms in PD arise due to selective degeneration of dopaminergic neurons in the substantia nigra of the ventral midbrain thereby depleting the dopamine levels in the striatum. Most of the current pharmacotherapeutic approaches in PD are aimed at replenishing the striatal dopamine. Although these drugs provide symptomatic relief during early PD, many patients develop motor complications with long-term treatment. Further, PD medications do not effectively tackle tremor, postural instability and cognitive deficits. Most importantly, most of these drugs do not exhibit neuroprotective effects in patients. Consequently, novel therapies involving natural antioxidants and plant products/molecules with neuroprotective properties are being exploited for adjunctive therapy. Curcumin is a polyphenol and an active component of turmeric (Curcuma longa), a dietary spice used in Indian cuisine and medicine. Curcumin exhibits antioxidant, anti-inflammatory and anti-cancer properties, crosses the blood-brain barrier and is neuroprotective in neurological disorders. Several studies in different experimental models of PD strongly support the clinical application of curcumin in PD. The current review explores the therapeutic potential of curcumin in PD.

  5. Morphine as a Potential Oxidative Stress-Causing Agent

    PubMed Central

    Skrabalova, Jitka; Drastichova, Zdenka; Novotny, Jiri

    2013-01-01

    Morphine exhibits important pharmacological effects for which it has been used in medical practice for quite a long time. However, it has a high addictive potential and can be abused. Long-term use of this drug can be connected with some pathological consequences including neurotoxicity and neuronal dysfunction, hepatotoxicity, kidney dysfunction, oxidative stress and apoptosis. Therefore, most studies examining the impact of morphine have been aimed at determining the effects induced by chronic morphine exposure in the brain, liver, cardiovascular system and macrophages. It appears that different tissues may respond to morphine diversely and are distinctly susceptible to oxidative stress and subsequent oxidative damage of biomolecules. Importantly, production of reactive oxygen/nitrogen species induced by morphine, which have been observed under different experimental conditions, can contribute to some pathological processes, degenerative diseases and organ dysfunctions occurring in morphine abusers or morphine-treated patients. This review attempts to provide insights into the possible relationship between morphine actions and oxidative stress. PMID:24376392

  6. Carbon nanotubes as delivery systems for respiratory disease: do the dangers outweigh the potential benefits?

    PubMed

    Bonner, James C

    2011-12-01

    Nanoparticle drug-delivery systems offer the potential for improved efficacy of treatment, and yet there are also potential risks associated with these novel therapeutic strategies. An attractive property of carbon nanotubes (CNTs) is that the tube- or fiber-like structure allows for extensive functionalization and loading of cargo. However, a large body of evidence indicates that CNTs may have adverse effects if used in drug delivery as they have been shown to cause pulmonary fibrosis and exacerbate lung disease in rodents with pre-existing lung diseases. Major factors that cause these toxic effects are the high aspect ratio, durability and residual metal content that generate reactive oxygen species. Therefore, careful consideration should be given to the possibility that lung inflammation or fibrosis could be significant side effects caused by a CNT-based drug-delivery system, thereby outweighing any potential beneficial effects of therapeutic treatment. However, functionalization of CNTs to modulate aspect ratio, biodegradability and to remove residual metals could allow for safe design of CNTs for use in drug delivery in certain circumstances.

  7. Water-soluble platinum phthalocyanines as potential antitumor agents.

    PubMed

    Bologna, Giuseppina; Lanuti, Paola; D'Ambrosio, Primiano; Tonucci, Lucia; Pierdomenico, Laura; D'Emilio, Carlo; Celli, Nicola; Marchisio, Marco; d'Alessandro, Nicola; Santavenere, Eugenio; Bressan, Mario; Miscia, Sebastiano

    2014-06-01

    Breast cancer represents the second cause of death in the European female population. The lack of specific therapies together with its high invasive potential are the major problems associated to such a tumor. In the last three decades platinum-based drugs have been considered essential constituents of many therapeutic strategies, even though with side effects and frequent generation of drug resistance. These drugs have been the guide for the research, in last years, of novel platinum and ruthenium based compounds, able to overcome these limitations. In this work, ruthenium and platinum based phthalocyanines were synthesized through conventional techniques and their antiproliferative and/or cytotoxic actions were tested. Normal mammary gland (MCF10A) and several models of mammarian carcinoma at different degrees of invasiveness (BT474, MCF-7 and MDA-MB-231) were used. Cells were treated with different concentrations (5-100 μM) of the above reported compounds, to evaluate toxic concentration and to underline possible dose-response effects. The study included growth curves made by trypan blue exclusion test and scratch assay to study cellular motility and its possible negative modulation by phthalocyanine. Moreover, we investigated cell cycle and apoptosis through flow cytometry and AMNIS Image Stream cytometer. Among all the tested drugs, tetrasulfonated phthalocyanine of platinum resulted to be the molecule with the best cytostatic action on neoplastic cell lines at the concentration of 30 μM. Interestingly, platinum tetrasulfophtalocyanine, at low doses, had no antiproliferative effects on normal cells. Therefore, such platinum complex, appears to be a promising drug for mammarian carcinoma treatment.

  8. Delivery methods for site-specific nucleases: Achieving the full potential of therapeutic gene editing.

    PubMed

    Liu, Jia; Shui, Sai-Lan

    2016-12-28

    The advent of site-specific nucleases, particularly CRISPR/Cas9, provides researchers with the unprecedented ability to manipulate genomic sequences. These nucleases are used to create model cell lines, engineer metabolic pathways, produce transgenic animals and plants, perform genome-wide functional screen and, most importantly, treat human diseases that are difficult to tackle by traditional medications. Considerable efforts have been devoted to improving the efficiency and specificity of nucleases for clinical applications. However, safe and efficient delivery methods remain the major obstacle for therapeutic gene editing. In this review, we summarize the recent progress on nuclease delivery methods, highlight their impact on the outcomes of gene editing and discuss the potential of different delivery approaches for therapeutic gene editing.

  9. Role of sodium tungstate as a potential antiplatelet agent.

    PubMed

    Fernández-Ruiz, Rebeca; Pino, Marc; Hurtado, Begoña; García de Frutos, Pablo; Caballo, Carolina; Escolar, Ginés; Gomis, Ramón; Diaz-Ricart, Maribel

    2015-01-01

    Platelet inhibition is a key strategy in the management of atherothrombosis. However, the large variability in response to current strategies leads to the search for alternative inhibitors. The antiplatelet effect of the inorganic salt sodium tungstate (Na2O4W), a protein tyrosine phosphatase 1B (PTP1B) inhibitor, has been investigated in this study. Wild-type (WT) and PTP1B knockout (PTP1B(-/-)) mice were treated for 1 week with Na2O4W to study platelet function with the platelet function analyzer PFA-100, a cone-and-plate analyzer, a flat perfusion chamber, and thrombus formation in vivo. Human blood aliquots were incubated with Na2O4W for 1 hour to measure platelet function using the PFA-100 and the annular perfusion chamber. Aggregometry and thromboelastometry were also performed. In WT mice, Na2O4W treatment prolonged closure times in the PFA-100 and decreased the surface covered (%SC) by platelets on collagen. Thrombi formed in a thrombosis mice model were smaller in animals treated with Na2O4W (4.6±0.7 mg vs 8.9±0.7 mg; P<0.001). Results with Na2O4W were similar to those in untreated PTP1B(-)/(-) mice (5.0±0.3 mg). Treatment of the PTP1B(-)/(-) mice with Na2O4W modified only slightly this response. In human blood, a dose-dependent effect was observed. At 200 μM, closure times in the PFA-100 were prolonged. On denuded vessels, %SC and thrombi formation (%T) decreased with Na2O4W. Neither the aggregating response nor the viscoelastic clot properties were affected. Na2O4W decreases consistently the hemostatic capacity of platelets, inhibiting their adhesive and cohesive properties under flow conditions in mice and in human blood, resulting in smaller thrombi. Although Na2O4W may be acting on platelet PTP1B, other potential targets should not be disregarded.

  10. Role of sodium tungstate as a potential antiplatelet agent

    PubMed Central

    Fernández-Ruiz, Rebeca; Pino, Marc; Hurtado, Begoña; García de Frutos, Pablo; Caballo, Carolina; Escolar, Ginés; Gomis, Ramón; Diaz-Ricart, Maribel

    2015-01-01

    Purpose Platelet inhibition is a key strategy in the management of atherothrombosis. However, the large variability in response to current strategies leads to the search for alternative inhibitors. The antiplatelet effect of the inorganic salt sodium tungstate (Na2O4W), a protein tyrosine phosphatase 1B (PTP1B) inhibitor, has been investigated in this study. Methods Wild-type (WT) and PTP1B knockout (PTP1B−/−) mice were treated for 1 week with Na2O4W to study platelet function with the platelet function analyzer PFA-100, a cone-and-plate analyzer, a flat perfusion chamber, and thrombus formation in vivo. Human blood aliquots were incubated with Na2O4W for 1 hour to measure platelet function using the PFA-100 and the annular perfusion chamber. Aggregometry and thromboelastometry were also performed. Results In WT mice, Na2O4W treatment prolonged closure times in the PFA-100 and decreased the surface covered (%SC) by platelets on collagen. Thrombi formed in a thrombosis mice model were smaller in animals treated with Na2O4W (4.6±0.7 mg vs 8.9±0.7 mg; P<0.001). Results with Na2O4W were similar to those in untreated PTP1B−/− mice (5.0±0.3 mg). Treatment of the PTP1B−/− mice with Na2O4W modified only slightly this response. In human blood, a dose-dependent effect was observed. At 200 μM, closure times in the PFA-100 were prolonged. On denuded vessels, %SC and thrombi formation (%T) decreased with Na2O4W. Neither the aggregating response nor the viscoelastic clot properties were affected. Conclusion Na2O4W decreases consistently the hemostatic capacity of platelets, inhibiting their adhesive and cohesive properties under flow conditions in mice and in human blood, resulting in smaller thrombi. Although Na2O4W may be acting on platelet PTP1B, other potential targets should not be disregarded. PMID:26060394

  11. β-Nitrostyrenes as Potential Anti-leishmanial Agents

    PubMed Central

    Shafi, Syed; Afrin, Farhat; Islamuddin, Mohammad; Chouhan, Garima; Ali, Intzar; Naaz, Faatima; Sharma, Kalicharan; Zaman, Mohammad S.

    2016-01-01

    Development of new therapeutic approach to treat leishmaniasis has become a priority. In the present study, the antileishmanial effect of β-nitrostyrenes was investigated against in vitro promastigotes and amastigotes. A series of β-nitrostyrenes have been synthesized by using Henry reaction and were evaluated for their antimicrobial activities by broth microdilution assay and in vitro antileishmanial activities against Leishmania donovani promastigotes by following standard guidelines. The most active compounds were futher evaluated for their in vitro antileishmanial activities against intracellular amastigotes. Among the tested β-nitrostyrenes, compounds 7, 8, 9, 12, and 17 exhibited potential activities (MICs range, 0.25–8 μg/mL) against clinically significant human pathogenic fungi. However, the microbactericidal concentrations (MBCs) and the microfungicidal concentrations (MFCs) were found to be either similar or only two-fold greater than the MICs. Anti-leishmanial results demonstrated that compounds 9, 12, 14, and 18 were found to be most active among the tested samples and exhibited 50% inhibitory concentration (IC50) by 23.40 ± 0.71, 37.83 ± 3.74, 40.50 ± 1.47, 55.66 ± 2.84 nM against L. donovani promastigotes and 30.5 ± 3.42, 21.46 ± 0.96, 26.43 ± 2.71, and 61.63 ± 8.02 nM respectively against intracellular L. donovani promastigotes amastigotes respectively which are comparable with standard AmB (19.60 ± 1.71 nM against promastigotes and 27.83 ± 3.26 nM against amastigotes). Compounds 9, 12, 14, and 18 were found to have potent in vitro leishmanicidal activity against L. donovani and found to be non-toxic against mammalian macrophages even at a concentration of 25 μM. Nitric oxide (NO) estimation studies reveals that these compounds are moderately inducing NO levels. PMID:27635124

  12. Nanofiber-based delivery of bioactive agents and stem cells to bone sites

    PubMed Central

    Zhang, Zhanpeng; Hu, Jiang; Ma, Peter X.

    2012-01-01

    Biodegradable nanofibers are important scaffolding materials for bone regeneration. In this paper, the basic concepts and recent advances of self-assembly, electrospinning and thermally induced phase separation techniques that are widely used to generate nanofibrous scaffolds are reviewed. In addition, surface functionalization and bioactive factor delivery within these nanofibrous scaffolds to enhance bone regeneration are also discussed. Moreover, recent progresses in applying these nanofiber-based scaffolds to deliver stem cells for bone regeneration are presented. Along with the significant advances, challenges and obstacles in the field as well as the future perspective are discussed. PMID:22579758

  13. Not so secret agents: Event-related potentials to semantic roles in visual event comprehension.

    PubMed

    Cohn, Neil; Paczynski, Martin; Kutas, Marta

    2017-09-09

    Research across domains has suggested that agents, the doers of actions, have a processing advantage over patients, the receivers of actions. We hypothesized that agents as "event builders" for discrete actions (e.g., throwing a ball, punching) build on cues embedded in their preparatory postures (e.g., reaching back an arm to throw or punch) that lead to (predictable) culminating actions, and that these cues afford frontloading of event structure processing. To test this hypothesis, we compared event-related brain potentials (ERPs) to averbal comic panels depicting preparatory agents (ex. reaching back an arm to punch) that cued specific actions with those to non-preparatory agents (ex. arm to the side) and patients that did not cue any specific actions. We also compared subsequent completed action panels (ex. agent punching patient) across conditions, where we expected an inverse pattern of ERPs indexing the differential costs of processing completed actions asa function of preparatory cues. Preparatory agents evoked a greater frontal positivity (600-900ms) relative to non-preparatory agents and patients, while subsequent completed actions panels following non-preparatory agents elicited a smaller frontal positivity (600-900ms). These results suggest that preparatory (vs. non-) postures may differentially impact the processing of agents and subsequent actions in real time. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Delivery

    PubMed Central

    Miller, Thomas A

    2013-01-01

    Enthusiasm greeted the development of synthetic organic insecticides in the mid-twentieth century, only to see this give way to dismay and eventually scepticism and outright opposition by some. Regardless of how anyone feels about this issue, insecticides and other pesticides have become indispensable, which creates something of a dilemma. Possibly as a result of the shift in public attitude towards insecticides, genetic engineering of microbes was first met with scepticism and caution among scientists. Later, the development of genetically modified crop plants was met with an attitude that hardened into both acceptance and hard-core resistance. Transgenic insects, which came along at the dawn of the twenty-first century, encountered an entrenched opposition. Those of us responsible for studying the protection of crops have been affected more or less by these protagonist and antagonistic positions, and the experiences have often left one thoughtfully mystified as decisions are made by non-participants. Most of the issues boil down to concerns over delivery mechanisms. © 2013 Society of Chemical Industry PMID:23852646

  15. Potential new approaches for the development of brain imaging agents for single-photon applications

    SciTech Connect

    Knapp, F.F. Jr.; Srivastava, P.C.

    1984-01-01

    This paper describes new strategies for the brain-specific delivery of radionuclides that can be used to evaluate regional cerebral perfusion by single photon imaging techniques. A description of several examples of interesting new strategies that have recently been reported is presented. A new approach at this institution for the brain-specific delivery of radioiodinated iodophenylalkyl-substituted dihyronicotinamide systems is described which shows good brain uptake and retention in preliminary studies in rats. Following transport into the brain these agents appear to undergo facile intracerebral oxidation to the quaternized analogues which do not recross the intact blood-brain barrier and so are effectively trapped in the brain. 49 refs., 9 figs., 1 tab.

  16. Modular Nanotransporters for Targeted Intracellular Delivery of Drugs: Folate Receptors as Potential Targets

    PubMed Central

    Slastnikova, Tatiana A.; Rosenkranz, Andrey A.; Zalutsky, Michael R.; Sobolev, Alexander S.

    2015-01-01

    The review is devoted to a subcellular drug delivery system, modular nanotransporters (MNT) that can penetrate into target cells and deliver a therapeutic into their subcellular compartments, particularly into the nucleus. The therapeutics which need such type of delivery belong to two groups: (i) those that exert their effect only when delivered into a certain cell compartment (like DNA delivered into the nucleus); and (ii) those drugs that are capable of exerting their effect in different parts of the cells, however there can be found a cell compartment that is the most sensitive to their effect. A particular interest attract such cytotoxic agents as Auger electron emitters which are known to be ineffective outside the cell nucleus, whereas they possess high cytotoxicity in the vicinity of nuclear DNA through the induction of non-reparable double-strand DNA breaks. The review discusses main approaches permitting to choose internalizable receptors permitting both recognition of target cells and penetration into them. Special interest attract folate receptors which become accessible to blood circulating therapeutics after malignant transformation or on activated macrophages which makes them an attractive target for both several oncological and inflammatory diseases, like atherosclerosis. In vitro and in vivo experiments demonstrated that MNT is a promising platform for targeted delivery of different therapeutics into the nuclei of target cells. PMID:25312738

  17. Biological activity of N(4)-boronated derivatives of 2'-deoxycytidine, potential agents for boron-neutron capture therapy.

    PubMed

    Nizioł, Joanna; Uram, Łukasz; Szuster, Magdalena; Sekuła, Justyna; Ruman, Tomasz

    2015-10-01

    Boron-neutron capture therapy (BNCT) is a binary anticancer therapy that requires boron compound for nuclear reaction during which high energy alpha particles and lithium nuclei are formed. Unnatural, boron-containing nucleoside with hydrophobic pinacol moiety was investigated as a potential BNCT boron delivery agent. Biological properties of this compound are presented for the first time and prove that boron nucleoside has low cytotoxicity and that observed apoptotic effects suggest alteration of important functions of cancer cells. Mass spectrometry analysis of DNA from cancer cells proved that boron nucleoside is inserted into nucleic acids as a functional nucleotide derivative. NMR studies present very high degree of similarity of natural dG-dC base pair with dG-boron nucleoside system. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Synthetic Ni3S2/Ni hybrid architectures as potential contrast agents in MRI

    NASA Astrophysics Data System (ADS)

    Ma, J.; Chen, K.

    2016-04-01

    Traditional magnetic resonance imaging (MRI) contrast agents mainly include superparamagnetic (SPM) iron oxide nanoparticle as T 2 contrast agent for liver and paramagnetic Gd (III)-chelate as T 1 contrast agent for all organs. In this work, weak ferromagnetic kale-like and SPM cabbage-like Ni3S2@Ni hybrid architectures were synthesized and evaluated as potential T 1 MRI contrast agents. Their relatively small r 2/r 1 ratios of 2.59 and 2.38, and high r 1 values of 11.27 and 4.89 mmol-1 L s-1 (for the kale-like and cabbage-like Ni3S2@Ni, respectively) will shed some light on the development of new-type MRI contrast agents.

  19. Synthesis and evaluation of degradable polyurea block copolymers as siRNA delivery agents.

    PubMed

    Cass, Peter; Knower, Warren; Hinton, Tracey; Shi, Shuning; Grusche, Felix; Tizard, Mark; Gunatillake, Pathiraja

    2013-09-01

    Chain extension by diisocyanate condensation provides a versatile and convenient means for preparing block copolymers. We have utilized this chemistry to prepare reducible multiblock polycations for siRNA delivery. This approach, an alternative to oxidative coupling, was suitable for preparing multiblock polycations with defined molecular weight and architecture. The polymer, PEG-b-multi-(polyhexylurea-co-oligo-L-lysine)-b-PEG, was capable of electrostatically condensing siRNA to form nano-sized polyplexes across a broad compositional range. We demonstrated that the polyplexes enter the cells via endocytosis and interact with the endosome membrane leading to destabilization and hence endosome escape. Another feature of these polymers is their multiple intra-chain disulfide linkages. This enables weakening of the polyplex via chain scission within the cytosol's reductive environment. In addition to the controlled preparation of the polymer, the polyplexes were capable of delivering siRNA in vitro to silence greater than 50% green fluorescent protein expression with negligible toxicity.

  20. pH-sensitive membrane peptides (pHLIPs) as a novel class of delivery agents

    PubMed Central

    Andreev, Oleg A.; Engelman, Donald M.; Reshetnyak, Yana K.

    2015-01-01

    Here we review a novel class of delivery vehicles based on pH-sensitive, moderately polar membrane peptides, which we call pH (Low) Insertion Peptides (pHLIPs), that target cells located in the acidic environment found in many diseased tissues, including tumors. SpecificAcidity targeting by pHLIPs is achieved as a result of helix formation and transmembrane insertion. In contrast to the earlier technologies based on cell-penetrating peptides, pHLIPs act as monomeric membrane-inserting peptides that translocate one terminus across a membrane into the cytoplasm, while the other terminus remains in the extracellular space, locating the peptide in the membrane lipid bilayer. Therefore,This geometry gives pHLIP has a dual delivery capability: it can tether cargo molecules or nanoparticles to the surfaces of cells in diseased tissues and/or it can move a cell-impermeable cargo molecule across the membrane into the cytoplasm. The source of energy for moving polar molecules attached to pHLIP through the hydrophobic layer of a membrane bilayer is the membrane-associated folding of the polypeptide. A drop in pH leads to the protonation of negatively charged residues (Asp or Glu), which enhances peptide hydrophobicity, increasing the affinity of the peptide for the lipid bilayer and triggering peptide folding and subsequent membrane insertion. The process is accompanied by the release of energy that can be utilized to move cell-impermeable cargo across a membrane. That the mechanism is now understood, and that targeting of tumors in mice has been shown, suggest a number of future applications of the pHLIP technology in the diagnosis and treatment of disease. PMID:20939768

  1. Natural resins and bioactive natural products thereof as potential antimicrobial agents.

    PubMed

    Termentzi, Aikaterini; Fokialakis, Nikolas; Skaltsounis, Alexios Leandros

    2011-01-01

    Natural products and their derivatives have historically been invaluable as a source of therapeutic agents and have contributed to the discovery of antimicrobial agents. However, today with the development of drug-resistant strains, new scaffolds and new sources of bioactive compounds are needed. To this end, plant derived natural resins are reviewed for their potential application as antimicrobial agents. Natural gums, extracts of the whole resins, as well as specific extracts, fractions, essential oils and isolated compounds from the above resins are discussed in terms of their antifungal, antibacterial, and antiprotozoal activity.

  2. Synthesis of amino Derivatives of Dithio Acids as Potential Radiation Protective Agents

    DTIC Science & Technology

    1984-08-01

    ation Management S SI ____ K> AD Synthesis of Amino Derivatives of Dithio Acids as Potential Radiation Protective Agents * 0 Annual Report "TIi: o DTIC...Sftcuntiy Clatuftcatio") Synthesis of Amino Derivatives of Dithio Acids as PotentitI- Radiation Protective Agents 12l PERISONAL. Ak.TI4OR(S) * William...methyl- picoline derivatives was accomplished. Use of N-mthyl-2,6-dimethylpyridine also allowed the synthesis of a bis(dithioacetic acid) function not

  3. The role of potential agents in making spatial perspective taking social

    PubMed Central

    Clements-Stephens, Amy M.; Vasiljevic, Katarina; Murray, Alexandra J.; Shelton, Amy L.

    2013-01-01

    A striking relationship between visual spatial perspective taking (VSPT) and social skills has been demonstrated for perspective-taking tasks in which the target of the imagined or inferred perspective is a potential agent, suggesting that the presence of a potential agent may create a social context for the seemingly spatial task of imagining a novel visual perspective. In a series of studies, we set out to investigate how and when a target might be viewed as sufficiently agent-like to incur a social influence on VSPT performance. By varying the perceptual and conceptual features that defined the targets as potential agents, we find that even something as simple as suggesting animacy for a simple wooden block may be sufficient. More critically, we found that experience with one potential agent influenced the performance with subsequent targets, either by inducing or eliminating the influence of social skills on VSPT performance. These carryover effects suggest that the relationship between social skills and VSPT performance is mediated by a complex relationship that includes the task, the target, and the context in which that target is perceived. These findings highlight potential problems that arise when identifying a task as belonging exclusively to a single cognitive domain and stress instead the highly interactive nature of cognitive domains and their susceptibility to cross-domain individual differences. PMID:24046735

  4. Preparation of thermo-responsive graft copolymer by using a novel macro-RAFT agent and its application for drug delivery.

    PubMed

    Song, Cunfeng; Yu, Shirong; Liu, Cheng; Deng, Yuanming; Xu, Yiting; Chen, Xiaoling; Dai, Lizong

    2016-05-01

    A methodology to prepare thermo-responsive graft copolymer by using a novel macro-RAFT agent was proposed. The macro-RAFT agent with pendant dithioester (ZC(S)SR) was facilely prepared via the combination of RAFT polymerization and esterification reaction. By means of ZC(S)SR-initiated RAFT polymerization, the thermo-responsive graft copolymer consisting of poly(methyl methacrylate-co-hydroxylethyl methacrylate) (P(MMA-co-HEMA)) backbone and hydrophilic poly(N-isopropylacrylamide) (PNIPAAm) side chains was constructed through the "grafting from" approach. The chemical compositions and molecular weight distributions of the synthesized polymers were respectively characterized by (1)H nuclear magnetic resonance ((1)H NMR) and gel permeation chromatography (GPC). Self-assembly behavior of the amphiphilic graft copolymers (P(MMA-co-HEMA)-g-PNIPAAm) was studied by transmission electron microscopy (TEM), dynamic light scattering (DLS) and spectrofluorimeter. The critical micelle concentration (CMC) value was 0.052 mg mL(-1). These micelles have thermo-responsibility and a low critical solution temperature (LCST) of 33.5°C. Further investigation indicated that the guest molecule release property of these micelles, which can be well described by a first-order kinetic model, was significantly affected by temperature. Besides, the micelles exhibited excellent biocompatibility and cellular uptake property. Hence, these micelles are considered to have potential application in controlled drug delivery.

  5. Long-term stability, biocompatibility and oral delivery potential of risperidone-loaded solid lipid nanoparticles.

    PubMed

    Silva, A C; Kumar, A; Wild, W; Ferreira, D; Santos, D; Forbes, B

    2012-10-15

    A solid lipid nanoparticles (SLN) formulation to improve the oral delivery of risperidone (RISP), a poorly water-soluble drug, was designed and tested. Initially, lipid-RISP solubility was screened to select the best lipid for SLN preparation. Compritol(®)-based formulations were chosen and their long-term stability was assessed over two years of storage (at 25 °C and 4 °C) by means of particle size, polydispersity index (PI), zeta potential (ZP) and encapsulation efficiency (EE) measurements. SLN shape was observed by transmission electron microscopy (TEM) at the beginning and end of the study. The oxidative potential (OP) of the SLN was measured and their biocompatibility with Caco-2 cells was evaluated using the (4,5-dimethylthiazol-2-yl)2,5-dyphenyl-tetrazolium bromide (MTT) assay. In vitro drug release and transport studies were performed to predict the in vivo release profile and to evaluate the drug delivery potential of the SLN formulations, respectively. The RISP-loaded SLN systems were stable and had high EE and similar shape to the placebo formulations before and after storage. Classical Fickian diffusion was identified as the release mechanism for RISP from the SLN formulation. Biocompatibility and dose-dependent RISP transport across Caco-2 cells were observed for the prepared SLN formulations. The viability of SLN as formulations for oral delivery of poorly water-soluble drugs such as RISP was illustrated.

  6. Exposure of hospital operating room personnel to potentially harmful environmental agents

    SciTech Connect

    Sass-Kortsak, A.M.; Purdham, J.T.; Bozek, P.R.; Murphy, J.H. )

    1992-03-01

    Epidemiologic studies of risk to reproductive health arising from the operating room environment have been inconclusive and lack quantitative exposure information. This study was undertaken to quantify exposure of operating room (OR) personnel to anesthetic agents, x-radiation, methyl methacrylate, and ethylene oxide and to determine how exposure varies with different operating room factors. Exposures of anesthetists and nurses to these agents were determined in selected operating rooms over three consecutive days. Each subject was asked to wear an x-radiation dosimeter for 1 month. Exposure to anesthetic agents was found to be influenced by the age of the OR facility, type of surgical service, number of procedures carried out during the day, type of anesthetic circuitry, and method of anesthesia delivery. Anesthetists were found to have significantly greater exposures than OR nurses. Exposure of OR personnel to ethylene oxide, methyl methacrylate, and x-radiation were well within existing standards. Exposure of anesthetists and nurses to anesthetic agents, at times, was in excess of Ontario exposure guidelines, despite improvements in the control of anesthetic pollution.

  7. Potential role of naturally derived polyphenols and their nanotechnology delivery in cancer.

    PubMed

    Khushnud, Tasnima; Mousa, Shaker A

    2013-09-01

    Polyphenols are natural compounds found in plants, fruits, chocolate, and beverages such as tea and wine. To date, the majority of polyphenol research shows them to have anticancer activity in cell lines and animal models. Some human clinical trials also indicate possible anticancer benefits are associated with polyphenols. A problem with polyphenols is their short half-life and low bioavailability; thus the use of nanoparticles to enhance their delivery is a new research field. A Pubmed search was conducted to find in vitro, in vivo, and human clinical trials done within the past 10 years involving the use of polyphenols against different cancer types, and for studies done within the past 5 years on the use of nanoparticles to enhance polyphenol delivery. Based on the studies found, it is observed that polyphenols may be a potential alternative or additive therapy against cancer, and the use of nanoparticles to enhance their delivery to tumors is a promising approach. However, further human clinical trials are necessary to better understand the use of polyphenols as well as their nanoparticle-mediated delivery.

  8. Sodium dependent multivitamin transporter (SMVT): a potential target for drug delivery.

    PubMed

    Vadlapudi, Aswani Dutt; Vadlapatla, Ramya Krishna; Mitra, Ashim K

    2012-06-01

    Sodium dependent multivitamin transporter (SMVT; product of the SLC5A6 gene) is an important transmembrane protein responsible for translocation of vitamins and other essential cofactors such as biotin, pantothenic acid and lipoic acid. Hydropathy plot (Kyte-Dolittle algorithm) revealed that human SMVT protein consists of 635 amino acids and 12 transmembrane domains with both amino and carboxyl termini oriented towards the cytoplasm. SMVT is expressed in various tissues such as placenta, intestine, brain, liver, lung, kidney, cornea, retina and heart. This transporter displays broad substrate specificity and excellent capacity for utilization in drug delivery. Drug absorption is often limited by the presence of physiological (epithelial tight junctions), biochemical (efflux transporters and enzymatic degradation) and chemical (size, lipophilicity, molecular weight, charge etc.) barriers. These barriers may cause many potential therapeutics to be dropped from the preliminary screening portfolio and subsequent entry into the market. Transporter targeted delivery has become a powerful approach to deliver drugs to target tissues because of the ability of the transporter to translocate the drug to intracellular organelles at a higher rate. This review highlights studies employing SMVT transporter as a target for drug delivery to improve bioavailability and investigate the feasibility of developing SMVT targeted drug delivery systems.

  9. Sodium Dependent Multivitamin Transporter (SMVT): A Potential Target for Drug Delivery

    PubMed Central

    Vadlapudi, Aswani Dutt; Vadlapatla, Ramya Krishna; Mitra, Ashim K.

    2015-01-01

    Sodium dependent multivitamin transporter (SMVT; product of the SLC5A6 gene) is an important transmembrane protein responsible for translocation of vitamins and other essential cofactors such as biotin, pantothenic acid and lipoic acid. Hydropathy plot (Kyte-Dolittle algorithm) revealed that human SMVT protein consists of 635 amino acids and 12 transmembrane domains with both amino and carboxyl termini oriented towards the cytoplasm. SMVT is expressed in various tissues such as placenta, intestine, brain, liver, lung, kidney, cornea, retina and heart. This transporter displays broad substrate specificity and excellent capacity for utilization in drug delivery. Drug absorption is often limited by the presence of physiological (epithelial tight junctions), biochemical (efflux transporters and enzymatic degradation) and chemical (size, lipophilicity, molecular weight, charge, etc.) barriers. These barriers may cause many potential therapeutics to be dropped from the preliminary screening portfolio and subsequent entry into the market. Transporter targeted delivery has become a powerful approach to deliver drugs to target tissues because of the ability of the transporter to translocate the drug to intracellular organelles at a higher rate. This review highlights studies employing SMVT transporter as a target for drug delivery to improve bioavailability and investigate the feasibility of developing SMVT targeted drug delivery systems. PMID:22420308

  10. PHB-Based Gels as Delivery Agents of Chemotherapeutics for the Effective Shrinkage of Tumors.

    PubMed

    Wu, Yun-Long; Wang, Han; Qiu, Ying-Kun; Liow, Sing Shy; Li, Zibiao; Loh, Xian Jun

    2016-10-01

    Injectable thermogel to deliver chemotherapeutics in a minimally invasive manner and to achieve their long term sustained release at tumor sites to minimize side effects is attractive for chemotherapy and precision medicine, but its rational design remains a challenge. In this work, a copolymer with natural biodegradable poly[(R)-3-hydroxybutyrate] (PHB), hydrophilic poly(ethylene glycol), and temperature sensitive poly(propylene glycol) blocks linked by urethane linkages is designed to show thermogelling characteristics which are beneficial for minimally invasive injection and safe degradation. This thermogelling polymer possesses in vitro biocompatibility with very low cyto-toxicity in HEK293 cells. Furthermore, it is able to form the gel to achieve the controllable release of paclitaxel (PTX) and doxorubicin (DOX) by adjusting polymer concentrations. A rodent model of hepatocarcinoma has been performed to demonstrate the in vivo applications of this PHB-based thermogel. The drug-loaded thermogel has been intratumorally injected and both PTX-loaded and DOX-loaded thermogel have significantly slowed down tumor growth. This work represents the first time that injectable PHB thermogels have possessed good controllable release effect of chemotherapeutics against the in vivo model of tumors and will benefit various applications, including on-demand drug delivery and personalized medicine.

  11. Targeted sustained delivery of antineoplastic agent with multicomponent polylactide stereocomplex micelle.

    PubMed

    Shen, Kexin; Li, Di; Guan, Jingjing; Ding, Jianxun; Wang, Zhongtang; Gu, Jingkai; Liu, Tongjun; Chen, Xuesi

    2017-04-01

    A c(RGDfC)-decorated polylactide stereocomplex micelle (cRGD-SCM) was prepared through the stereocomplex and hydrophobic interactions among 4-arm poly(ethylene glycol)-block-poly(D-lactide) (4-arm PEG-b-PDLA), methoxy poly(ethylene glycol)-block-poly(L-lactide) (mPEG-b-PLLA), and c(RGDfC)-poly(ethylene glycol)-block-poly(L-lactide) (cRGD-PEG-b-PLLA) for targeted treatment of αvβ3 integrin-positive C26 colon cancer. Doxorubicin (DOX), a model antitumor drug, was loaded into cRGD-SCM with a diameter of approximately 100nm, and the drug loading efficiency was 45.9wt.%. cRGD-SCM/DOX with a sustained release pattern exhibited prolonged circulation time, upregulated accumulation in tumor, enhanced tumor inhibition, and decreased side effects compared with free DOX and non-targeting SCM/DOX in vivo. More interestingly, the targeting ligand in the terminal of PEG can be easily replaced with other targeting groups according to the different types of malignancies. Therefore, the cRGD-decorated platform might be a promising targeted drug delivery system for personal chemotherapy clinically. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Temperature-Responsive Smart Nanocarriers for Delivery Of Therapeutic Agents: Applications and Recent Advances.

    PubMed

    Karimi, Mahdi; Sahandi Zangabad, Parham; Ghasemi, Alireza; Amiri, Mohammad; Bahrami, Mohsen; Malekzad, Hedieh; Ghahramanzadeh Asl, Hadi; Mahdieh, Zahra; Bozorgomid, Mahnaz; Ghasemi, Amir; Rahmani Taji Boyuk, Mohammad Reza; Hamblin, Michael R

    2016-08-24

    Smart drug delivery systems (DDSs) have attracted the attention of many scientists, as carriers that can be stimulated by changes in environmental parameters such as temperature, pH, light, electromagnetic fields, mechanical forces, etc. These smart nanocarriers can release their cargo on demand when their target is reached and the stimulus is applied. Using the techniques of nanotechnology, these nanocarriers can be tailored to be target-specific, and exhibit delayed or controlled release of drugs. Temperature-responsive nanocarriers are one of most important groups of smart nanoparticles (NPs) that have been investigated during the past decades. Temperature can either act as an external stimulus when heat is applied from the outside, or can be internal when pathological lesions have a naturally elevated termperature. A low critical solution temperature (LCST) is a special feature of some polymeric materials, and most of the temperature-responsive nanocarriers have been designed based on this feature. In this review, we attempt to summarize recent efforts to prepare innovative temperature-responsive nanocarriers and discuss their novel applications.

  13. Mathematical modeling analysis of intratumoral disposition of anticancer agents and drug delivery systems.

    PubMed

    Popilski, Hen; Stepensky, David

    2015-05-01

    Solid tumors are characterized by complex morphology. Numerous factors relating to the composition of the cells and tumor stroma, vascularization and drainage of fluids affect the local microenvironment within a specific location inside the tumor. As a result, the intratumoral drug/drug delivery system (DDS) disposition following systemic or local administration is non-homogeneous and its complexity reflects the differences in the local microenvironment. Mathematical models can be used to analyze the intratumoral drug/DDS disposition and pharmacological effects and to assist in choice of optimal anticancer treatment strategies. The mathematical models that have been applied by different research groups to describe the intratumoral disposition of anticancer drugs/DDSs are summarized in this article. The properties of these models and of their suitability for prediction of the drug/DDS intratumoral disposition and pharmacological effects are reviewed. Currently available mathematical models appear to neglect some of the major factors that govern the drug/DDS intratumoral disposition, and apparently possess limited prediction capabilities. More sophisticated and detailed mathematical models and their extensive validation are needed for reliable prediction of different treatment scenarios and for optimization of drug treatment in the individual cancer patients.

  14. Fabrication of biodendrimeric β-cyclodextrin via click reaction with potency of anticancer drug delivery agent.

    PubMed

    Toomari, Yousef; Namazi, Hassan; Entezami, Ali Akbar

    2015-08-01

    The aim of this work was the synthesis of biodendrimeric β-cyclodextrin (β-CD) on the secondary face with encapsulation efficacy, with β-CDs moiety to preserve the biocompatibility properties, also particularly growth their loading capacity for drugs with certain size. The new dendrimer, having 14 β-CD residues attached to the core β-CD in secondary face (11), was prepared through click reaction. The encapsulation property of the prepared compound was evaluated by methotrexate (MTX) drug molecule. Characterization of compound 11 was performed with (1)H NMR, (13)C NMR and FTIR and its supramolecular inclusion complex structure was determined using FTIR, DLS, DSC and SEM techniques. In vitro cytotoxicity test results showed that compound 11 has very low or no cytotoxic effect on T47D cancer cells. In vitro drug release study at pHs 3, 5 and 7.4 showed that the release process was noticeably pH dependent and the dendrimer could be used as an appropriate controlled drug delivery system (DDS) for cancer treatment.

  15. Image-guided robotic delivery system for precise placement of therapeutic agents.

    PubMed

    Cleary, K; Freedman, M; Clifford, M; Lindisch, D; Onda, S; Jiang, L

    2001-07-06

    The effectiveness of conventional solid tumor treatment is limited by the systemic toxicity and lack of specificity of chemotherapeutic agents. Present treatment modalities are frequently insufficient to eliminate competent cancer cells without exceeding the limits of toxicity to normal tissue. The coming generation of cancer therapeutics depends on the precise targeting and sustained release of antitumor agents to overcome these limitations. We are developing an image-guided, robotic system for precise intratumoral placement of anticancer drugs and sustained release devices to advance this new treatment paradigm. The robotic system will use intraoperatively obtained computed tomographic (CT) images from a mobile CT scanner for guidance. The concept is to track patient anatomy and localize instruments using currently available optical tracking technology. Tracking will also be used to register patient anatomy with the images. The physician can then use the registered image to select an appropriate tumor target and entry location and to plan the instrument path. This path will then be transmitted to the robot, which orients and drives the instrument to the desired target under physician control. Achievement of the target is confirmed via intraoperative CT. This system will provide instrument guidance that is precise, direct, and controllable. Error due to poor target visualization and hand unsteadiness should be reduced greatly. The basic components of the system (robot, mobile CT, tracking) have been demonstrated in our laboratory, and the integration of the components is in progress. In future work, we plan to fuse preoperative PET imaging with intraoperative CT to allow functional as well as anatomic image guidance.

  16. Antinuclear antibodies with nucleosome-restricted specificity for targeted delivery of chemotherapeutic agents.

    PubMed

    Torchilin, Vladimir P

    2010-08-01

    Circulating antinuclear autoantibodies (ANAs) are well known to accompany various pathological conditions and can be artificially induced by immunization. Research and clinical data permit us to hypothesize a definite connection between cancer and ANAs. Based on the available data, my group's research suggested that exogenous ANAs may be used as anticancer therapeutics. Among these ANAs, nucleosome-specific ANAs may be particularly useful. Advances in cancer immunotherapy with monoclonal antibodies re-emphasized the role of humoral immunity in neoplasia control. The development of a universal antibody targeting diverse cancers is of clear importance. We showed that certain natural ANAs recognize the surface of numerous tumor cells but not normal cells via cell surface-bound nucleosomes originating from the apoptotically dying neighboring tumor cells, mediate antibody-dependent cellular cytotoxicity of tumor cells in vitro and inhibit the development of murine tumor in syngeneic mice. A single monoclonal antinuclear nucleosome-specific autoantibody, mAb 2C5, specifically recognizes multiple unrelated human tumor cell lines and accumulates at a high tumor-to-normal cell ratio in various human tumors in nude mice. Immunotherapy with mAb 2C5 resulted in significant suppression of the growth of several human tumors. In addition, mAb 2C5, when used in subtherapeutic quantities, can serve as a highly efficient specific ligand to target various drug- or diagnostic agent-loaded pharmaceutical nanocarriers, such as liposomes and polymeric micelles, to various tumors. Here, the data (accumulated predominantly in our laboratory over several years) on mAb 2C5-mediated tumor targeting of chemotherapeutic agents is reviewed.

  17. The Mouse Round-window Approach for Ototoxic Agent Delivery: A Rapid and Reliable Technique for Inducing Cochlear Cell Degeneration

    PubMed Central

    Stevens, Shawn M.; Brown, LaShardai N.; Ezell, Paula C.; Lang, Hainan

    2015-01-01

    Investigators have utilized a wide array of animal models and investigative techniques to study the mammalian auditory system. Much of the basic research involving the cochlea and its associated neural pathways entails exposure of model cochleae to a variety of ototoxic agents. This allows investigators to study the effects of targeted damage to cochlear structures, and in some cases, the self-repair or regeneration of those structures. Various techniques exist for delivery of ototoxic agents to the cochlea. When selecting a particular technique, investigators must consider a number of factors, including the induction of inadvertent systemic toxicity, the amount of cochlear damage produced by the surgical procedure itself, the type of lesion desired, animal survivability, and reproducibility/reliability of results. Currently established techniques include parenteral injection, intra-peritoneal injection, trans-tympanic injection, endolymphatic sac injection, and cochleostomy with perilymphatic perfusion. Each of these methods has been successfully utilized and is well described in the literature; yet, each has various shortcomings. Here, we present a technique for topical application of ototoxic agents directly to the round window niche. This technique is non-invasive to inner ear structures, produces rapid onset of reliably targeted lesions, avoids systemic toxicity, and allows for an intra-animal control (the contra-lateral ear). Results stemming from this approach have helped deeper understanding of auditory pathophysiology, cochlear cell degeneration, and regenerative capacity in response to an acute injury. Future investigations may use this method to conduct interventional studies involving gene therapy and stem cell transplantation to combat hearing loss. PMID:26650771

  18. Lactoferrin bioconjugated solid lipid nanoparticles: a new drug delivery system for potential brain targeting.

    PubMed

    Singh, Indu; Swami, Rajan; Pooja, Deep; Jeengar, Manish Kumar; Khan, Wahid; Sistla, Ramakrishna

    2016-01-01

    Delivery of drugs to brain is a subtle task in the therapy of many severe neurological disorders. Solid lipid nanoparticles (SLN) easily diffuse the blood-brain barrier (BBB) due to their lipophilic nature. Furthermore, ligand conjugation on SLN surface enhances the targeting efficiency. Lactoferin (Lf) conjugated SLN system is first time attempted for effective brain targeting in this study. Preparation of Lf-modified docetaxel (DTX)-loaded SLN for proficient delivery of DTX to brain. DTX-loaded SLN were prepared using emulsification and solvent evaporation method and conjugation of Lf on SLN surface (C-SLN) was attained through carbodiimide chemistry. These lipidic nanoparticles were evaluated by DLS, AFM, FTIR, XRD techniques and in vitro release studies. Colloidal stability study was performed in biologically simulated environment (normal saline and serum). These lipidic nanoparticles were further evaluated for its targeting mechanism for uptake in brain tumour cells and brain via receptor saturation studies and distribution studies in brain, respectively. Particle size of lipidic nanoparticles was found to be optimum. Surface morphology (zeta potential, AFM) and surface chemistry (FTIR) confirmed conjugation of Lf on SLN surface. Cytotoxicity studies revealed augmented apoptotic activity of C-SLN than SLN and DTX. Enhanced cytotoxicity was demonstrated by receptor saturation and uptake studies. Brain concentration of DTX was elevated significantly with C-SLN than marketed formulation. It is evident from the cytotoxicity, uptake that SLN has potential to deliver drug to brain than marketed formulation but conjugating Lf on SLN surface (C-SLN) further increased the targeting potential for brain tumour. Moreover, brain distribution studies corroborated the use of C-SLN as a viable vehicle to target drug to brain. Hence, C-SLN was demonstrated to be a promising DTX delivery system to brain as it possessed remarkable biocompatibility, stability and efficacy than

  19. Synthesis and characterization of perfluoro-tert-butyl semifluorinated amphiphilic polymers and their potential application in hydrophobic drug delivery

    PubMed Central

    Decato, Sarah; Bemis, Troy; Madsen, Eric; Mecozzi, Sandro

    2014-01-01

    Semifluorinated polymer surfactants, composed of a monomethyl poly(ethylene glycol) (mPEG) hydrophilic head group and either 1, 2, or 3 perfluoro-tert-butyl (PFtB) groups as the fluorophilic tail, were synthesized, and their aqueous self-assemblies were investigated as a potential design for theranostic nanoparticles. Polymers with three PFtB groups (PFtBTRI) solely formed stable, spherical micelles, approximately 12 nm in size. These PFtBTRI surfactants demonstrate similar characteristics with those of polymers with linear perfluorocarbon tails, despite large differences in tail structure. For example, PFtB polymer solutions stably emulsified 20 v/v% sevoflurane with perfluorooctyl bromide (PFOB) as a stabilizer. However, these PFtB polymers have the additional potential to serve as F-MRI contrast agents. PFtBTRI micelles gave one narrow 19F-NMR signal in D2O, with T1 and T2 parameters of approximately 500 and 100 ms, respectively. 19F-MR images of PFtB polymer solutions at 1 mM gave intense signal at 4.7 T without sensitizers or selective excitation sequences. These preliminary data demonstrate the potential of PFtB polymers as a basic design, which can be further modified to serve as dual drug-delivery and imaging vehicles. PMID:25383100

  20. Nanotechnology As Potential Tool for siRNA Delivery in Parkinson's Disease.

    PubMed

    Cortés, Hernán; Alcalá-Alcalá, Sergio; Ávalos-Fuentes, Arturo; Mendoza-Muñoz, Nestor; Quintanar-Guerrero, David; Leyva-Gómez, Gerardo; Florán, Benjamín

    2017-03-21

    The lack of an outright treatment for Parkinson's disease (PD) is a pivotal concern in medicine and has driven the search for novel alternatives for treating the disease. Among the proposed approaches, small interfering RNA (siRNA)-based therapy is attracting significant attention as a potential method for the treatment of PD; however, siRNAs delivery possesses potential drawbacks, such as reduced stability in blood circulation and low capacity for reaching the target site. Therefore, siRNA delivery to the brain is a key issue that remains unsolved to date. In this regard, nanoparticles are being developed as carriers for siRNAs and represent an alternative to common vectors; the formulation of siRNAs in nanoparticles would possess several advantages over other vectors, such as controlled delivery and low toxicity profiles. Therefore, in this article we focus on siRNA-based approaches to PD and the latest advances for designing nanoparticles that effectively target siRNAs to the action site and that protect these against degradation in blood circulation. Additionally, we discuss the technological aspects for tackling the challenge that siRNAs targeting to the brain represents.

  1. Thiolated methylated dimethylaminobenzyl chitosan: A novel chitosan derivative as a potential delivery vehicle.

    PubMed

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

    2017-02-01

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

  2. Cytoplasmic RNA viruses as potential vehicles for the delivery of therapeutic small RNAs.

    PubMed

    Usme-Ciro, Jose A; Campillo-Pedroza, Natalia; Almazán, Fernando; Gallego-Gomez, Juan C

    2013-06-07

    Viral vectors have become the best option for the delivery of therapeutic genes in conventional and RNA interference-based gene therapies. The current viral vectors for the delivery of small regulatory RNAs are based on DNA viruses and retroviruses/lentiviruses. Cytoplasmic RNA viruses have been excluded as viral vectors for RNAi therapy because of the nuclear localization of the microprocessor complex and the potential degradation of the viral RNA genome during the excision of any virus-encoded pre-microRNAs. However, in the last few years, the presence of several species of small RNAs (e.g., virus-derived small interfering RNAs, virus-derived short RNAs, and unusually small RNAs) in animals and cell cultures that are infected with cytoplasmic RNA viruses has suggested the existence of a non-canonical mechanism of microRNA biogenesis. Several studies have been conducted on the tick-borne encephalitis virus and on the Sindbis virus in which microRNA precursors were artificially incorporated and demonstrated the production of mature microRNAs. The ability of these viruses to recruit Drosha to the cytoplasm during infection resulted in the efficient processing of virus-encoded microRNA without the viral genome entering the nucleus. In this review, we discuss the relevance of these findings with an emphasis on the potential use of cytoplasmic RNA viruses as vehicles for the efficient delivery of therapeutic small RNAs.

  3. Cubosomes and other potential ocular drug delivery vehicles for macromolecular therapeutics.

    PubMed

    Hartnett, Terence E; O'Connor, Andrea J; Ladewig, Katharina

    2015-01-01

    Many macromolecular therapeutics designed to treat posterior segment eye diseases (PSEDs) are administered through frequent ocular injection, which can further deteriorate eye health. Due to the high frequency of injection and the high cost of the therapeutics, there is a need to develop new ways in which to deliver these therapeutics: ways which are both safer and more cost effective. Using the most common PSED, age-related macular degeneration, as an example of a debilitating ocular disease, this review examines the key barriers limiting the delivery of macromolecular therapeutics to the posterior segment of the eye and defines the key requirements placed on particulate drug delivery vehicles (DDVs) to be suitable for this application. Recent developments in macromolecular drug delivery to treat this disease as well as the remaining shortcomings in its treatment are surveyed. Lastly, an emerging class of DDVs potentially suited to this application, called cubosomes, is introduced. Based on their excellent colloidal stability and high internal surface area, cubosomes hold great potential for the sustained release of therapeutics. Novel production methods and a better understanding of the mechanisms through which drug release from these particles can be controlled are two major recent developments toward successful application.

  4. Realizing the Potential of Vascular Targeted Therapy: The Rationale for Combining Vascular Disrupting Agents and Anti-Angiogenic Agents to Treat Cancer.

    PubMed

    Siemann, D W; Chaplin, D J; Horsman, M R

    2017-09-14

    Vascular targeted therapies (VTTs) are agents that target tumor vasculature and can be classified into two categories: those that inhibit angiogenesis and those that directly interfere with established tumor vasculature. Although both the anti-angiogenic agents (AAs) and the vascular disrupting agents (VDAs) target tumor vasculature, they differ in their mechanism of action and therapeutic application. Combining these two agents may realize the full potential of VTT and produce an effective therapeutic regimen. Here, we review AAs and VDAs (monotherapy and in combination with conventional therapies). We also discuss the rationale of combined VTT and its potential to treat cancer.

  5. In-flight food delivery and waste collection service: the passengers’ perspective and potential improvement

    NASA Astrophysics Data System (ADS)

    Romli, F. I.; Rahman, K. Abdul; Ishak, F. D.

    2016-10-01

    Increased competition in the commercial air transportation industry has made service quality of the airlines as one of the key competitive measures to attract passengers against their rivals. In-flight services, particularly food delivery and waste collection, have a notable impact on perception of the overall airline's service quality because they are directly and interactively provided to passengers during flight. An online public survey is conducted to explore general passengers' perception of current in-flight food delivery and waste collection services, and to identify potential rooms for improvement. The obtained survey results indicate that in-flight service does have an effect on passengers' choice of airlines. Several weaknesses of the current service method and possible improvements have been established from the collected responses.

  6. Redox Potential Ultrasensitive Nanoparticle for the Targeted Delivery of Camptothecin to HER2-Positive Cancer Cells

    PubMed Central

    2015-01-01

    Ideal “smart” nanoparticles for drug delivery should enhance therapeutic efficacy without introducing side effects. To achieve that, we developed a drug delivery system (HCN) based on a polymer–drug conjugate of poly[2-(pyridin-2-yldisulfanyl)]-graft-poly(ethylene glycol) and camptothecin with an intracellularly cleavable linker and human epidermal growth factor receptor 2 (HER2) targeting ligands. An in vitro drug release study found that HCN was stable in the physiological environment and supersensitive to the stimulus of elevated intracellular redox potential, releasing all payloads in less than 30 min. Furthermore, confocal microscopy revealed that HCN could specifically enter HER2-positive cancer cells. As a consequence, HCN could effectively kill HER2-positive cancer cells while not affecting HER2-negative cells. PMID:24779647

  7. Immunity under the skin: potential application for topical delivery of vaccines.

    PubMed

    Partidos, C D; Beignon, A-S; Mawas, F; Belliard, G; Briand, J-P; Muller, S

    2003-01-30

    With the technological advances in biomedical sciences and the better understanding of how the immune system works, new immunisation strategies and vaccine delivery options, such sprays, patches, and edible formulations have been developed. This has opened up the possibility of administering vaccines without the use of needles and syringes. Already topical immunisation is a reality and it has the potential to make vaccine delivery more equitable, safer, and efficient. Furthermore, it would increase the rate of vaccine compliance and greatly facilitate the successful implementation of worldwide mass vaccination campaigns against infectious diseases. This review gives a brief account of the latest developments of application of candidate vaccine antigens onto bare skin and describes some of our recent observations using peptide and glycoconjugate vaccines as immunogens.

  8. Agents.

    PubMed

    Chambers, David W

    2002-01-01

    Although health care is inherently an economic activity, it is inadequately described as a market process. An alternative, grounded in organizational economic theory, is to view professionals and many others as agents, contracted to advance the best interests of their principals (patients). This view untangles some of the ethical conflicts in dentistry. It also helps identify major controllable costs in dentistry and suggests that dentists can act as a group to increase or decrease agency costs, primarily by controlling the bad actors who damage the value of all dentists.

  9. Impact of wine manufacturing practice on the occurrence of fining agents with allergenic potential.

    PubMed

    Deckwart, Marina; Carstens, Carsten; Webber-Witt, Manuella; Schäfer, Volker; Eichhorn, Lisa; Schröter, Franziska; Fischer, Markus; Brockow, Knut; Christmann, Monika; Paschke-Kratzin, Angelika

    2014-01-01

    Proteinogenic wine fining agents are hidden allergens and could present a risk for consumers with allergies. Therefore, the European Parliament adopted Directive 2003/89/EC amending Directive 2000/13/EC to declare ingredients, contaminations and processing aids that are known to trigger allergic reactions. The Amendment Regulation (EU) 1266/2010 excluded the labelling of wines which are processed with hen's egg and products thereof until 30 June 2012 to get more scientific findings. After 1 July 2012 wine fining agents have to be declared if above 0.25 mg l(-1) (Regulation (EU) 579/2012 in conjunction with article 120 g of Regulation (EU) 1234/2007). The Organisation International de la Vigne et du Vin (OIV) advises this limit of detection (LOD) for potential allergenic residues of proteins. Wine fining agents are processing aids and according to the wine producer's knowledge will be removed after coagulation by filtration or other production steps. Due to lack of scientific data, residues of fining agents in the final product could not be excluded. In this risk assessment, highly sensitive ELISA methods for ovalbumin of known origin for wine have been developed. The objective was to investigate the presence of allergen residues in wine after certain technological treatments were applied to remove the wine fining agents. For all developed ELISA methods the LODs are in the low µg l(-1) range between 5 and 10 µg l(-1) fining agent, whereas the LOQ varies between 5 and 80 µg l(-1) fining agent. The results of the investigation of well-known wines and fining agents demonstrate that white wines fined with white or ovalbumin from hen's egg could retain allergens. The use of certain technological procedures during wine processing leads to different results. In white wine, bentonite or sheet filtration followed by sterile filtration lead to wines containing no detectable amounts of ovalbumin. In red wine, especially the final sterile filtration removes the fining agents.

  10. Macromolecular Imaging Agents Containing Lanthanides: Can Conceptual Promise Lead to Clinical Potential?

    PubMed Central

    Bryson, Joshua; Reineke, Jeffrey W.; Reineke, Theresa M.

    2012-01-01

    Macromolecular magnetic resonance imaging (MRI) contrast agents are increasingly being used to improve the resolution of this noninvasive diagnostic technique. All clinically-approved T1 contrast agents are small molecule chelates of gadolinium [Gd(III)] that affect bound water proton relaxivity. Both the small size and monomeric nature of these agents ultimately limits the image resolution enhancement that can be achieved for both contrast enhancement and pharmacokinetic/biodistribution reasons. The multimeric nature of macromolecules, such as polymers, dendrimers, and noncovalent complexes of small molecule agents with proteins, have been shown to significantly increase the image contrast and resolution due to their large size and ability to incorporate multiple Gd(III) chlelation sites. Also, macromolecular agents are advantageous as they have the ability to be designed to be nontoxic, hydrophilic, easily purified, aggregation-resistant, and have controllable three-dimensional macromolecular structure housing the multiple lanthanide chelation sites. For these reasons, large molecule diagnostics have the ability to significantly increase the relaxivity of water protons within the targeted tissues and thus the image resolution for many diagnostic applications. The FDA approval of a contrast agent that consists of a reversible, non-covalent coupling of a small Gd(III) chelate with serum albumin for blood pool imaging (marketed under the trade names of Vasovist and Ablivar) proved to be one of the first diagnostic agent to capitalize on these benefits from macromolecular association in humans. However, much research and development is necessary to optimize the safety of these unique agents for in vivo use and potential clinical development. To this end, recent work in the field of polymer, dendrimer, and noncovalent complex-based imaging agents are reviewed herein and the future outlook of this field is discussed. PMID:23467737

  11. Potential use of polymeric nanoparticles for drug delivery across the blood-brain barrier.

    PubMed

    Tosi, G; Bortot, B; Ruozi, B; Dolcetta, D; Vandelli, M A; Forni, F; Severini, G M

    2013-01-01

    Nanomedicine is certainly one of the scientific and technological challenges of the coming years. In particular, biodegradable nanoparticles formulated from poly (D,L-lactide-co-glycolide) (PLGA) have been extensively investigated for sustained and targeted delivery of different agents, including recombinant proteins, plasmid DNA, and low molecular weight compounds. PLGA NPs present some very attractive properties such as biodegradability and biocompatibility, protection of drug from degradation, possibility of sustained release, and the possibility to modify surface properties to target nanoparticles to specific organs or cells. Moreover, PLGA NPs have received the FDA and European Medicine Agency approval in drug delivery systems for parenteral administration, thus reducing the time for human clinical applications. This review in particular deals on surface modification of PLGA NPs and their possibility of clinical applications, including treatment for brain pathologies such as brain tumors and Lysosomal Storage Disorders with neurological involvement. Since a great number of pharmacologically active molecules are not able to cross the Blood-Brain Barrier (BBB) and reach the Central Nervous System (CNS), new brain targeted polymeric PLGA NPs modified with glycopeptides (g7- NPs) have been recently produced. In this review several in vivo biodistribution studies and pharmacological proof-of evidence of brain delivery of model drugs are reported, demonstrating the ability of g7-NPs to create BBB interaction and trigger an efficacious BBB crossing. Moreover, another relevant development of NPs surface engineering was achieved by conjugating to the surface of g7-NPs, some specific and selective antibodies to drive NPs directly to a specific cell type once inside the CNS parenchyma.

  12. The exciting potential of nanotherapy in brain-tumor targeted drug delivery approaches

    PubMed Central

    Agrahari, Vivek

    2017-01-01

    Delivering therapeutics to the central nervous system (CNS) and brain-tumor has been a major challenge. The current standard treatment approaches for the brain-tumor comprise of surgical resection followed by immunotherapy, radiotherapy, and chemotherapy. However, the current treatments are limited in providing significant benefits to the patients and despite recent technological advancements; brain-tumor is still challenging to treat. Brain-tumor therapy is limited by the lack of effective and targeted strategies to deliver chemotherapeutic agents across the blood-brain barrier (BBB). The BBB is the main obstacle that must be overcome to allow compounds to reach their targets in the brain. Recent advances have boosted the nanotherapeutic approaches in providing an attractive strategy in improving the drug delivery across the BBB and into the CNS. Compared to conventional formulations, nanoformulations offer significant advantages in CNS drug delivery approaches. Considering the above facts, in this review, the physiological/anatomical features of the brain-tumor and the BBB are briefly discussed. The drug transport mechanisms at the BBB are outlined. The approaches to deliver chemotherapeutic drugs across the CNS into the brain-tumor using nanocarriers are summarized. In addition, the challenges that need to be addressed in nanotherapeutic approaches for their enhanced clinical application in brain-tumor therapy are discussed. PMID:28400793

  13. Potential approaches for drug delivery to the brain: past, present, and future.

    PubMed

    Soni, V; Jain, A; Khare, P; Gulbake, A; Jain, S K

    2010-01-01

    The objective of this article is to provide the reader with an update on some research highlights from the past to the present, as well as future possibilities to achieve improved delivery of drugs across the blood-brain barrier (BBB). In the past, dye studies confirmed the presence of the BBB and blood-cerebrospinal fluid barriers, which seem to play a major role in transporting drug molecules for the treatment of life-threatening diseases such as brain cancer and Alzheimer's. Presently, transportation mechanisms such as simple diffusion, carrier-mediated, absorptive-mediated, and receptor-mediated transcytosis are extensively used for BBB uptake of drug molecules. The spectrum of future neuropharmaceuticals falling into these categories ranges from peptides to nucleotide-based drugs as well as gene and stem cell delivery agents, and is increasing at a rapid rate with promising results. There has also been considerable progress in the development of quantitative methods to examine BBB permeability in humans and animals. Currently, intravenous administration and in situ brain perfusion techniques are the most versatile and sensitive methods to measure transport into the brain. This article also reviews the various methodologies available for assessing the transfer of drug molecules undergoing significant uptake through the BBB in vivo.

  14. MRI-visible liposome nanovehicles for potential tumor-targeted delivery of multimodal therapies

    NASA Astrophysics Data System (ADS)

    Ren, Lili; Chen, Shizhen; Li, Haidong; Zhang, Zhiying; Ye, Chaohui; Liu, Maili; Zhou, Xin

    2015-07-01

    Real-time diagnosis and monitoring of disease development, and therapeutic responses to treatment, are possible by theranostic magnetic resonance imaging (MRI). Here we report the synthesis of a multifunctional liposome, which contains Gd-DOTA (an MRI probe), paclitaxel and c(RGDyk) (a targeted peptide). This nanoparticle overcame the insolubility of paclitaxel, reduced the side effects of FDA-approved formulation of PTX-Cre (Taxol®) and improved drug delivery efficiency to the tumor. c(RGDyk) modification greatly enhanced the cytotoxicity of the drug in tumor cells A549. The T1 relaxivity in tumor cells treated with the targeted liposome formulation was increased 16-fold when compared with the non-targeted group. In vivo, the tumors in mice were visualized using T1-weighted imaging after administration of the liposome. Also the tumor growth could be inhibited well after the treatment. Fluorescence images in vitro and ex vivo also showed the targeting effect of this liposome in tumor cells, indicating that this nanovehicle could limit the off-target side effects of anticancer drugs and contrast agents. These findings lay the foundation for further tumor inhibition study and application of this delivery vehicle in cancer therapy settings.

  15. Interventional MRI-guided local delivery of agents into swine bile duct walls using MR-compatible needle-integrated balloon catheter system.

    PubMed

    Zhang, Feng; Bai, Zhibin; Shi, Yaoping; Wang, Jianfeng; Li, Yonggang; Yang, Xiaoming

    2015-06-01

    The purpose of this study was to investigate the feasibility of interventional MRI-guided local agent delivery into pig common bile duct (CBD) walls using a newly designed MR-compatible, needle-integrated balloon catheter system. We first designed a needle-integrated balloon catheter system that comprised of a 22 G MR-compatible Chiba biopsy needle and a conventional 12 mm × 2 cm balloon catheter. Under fluoroscopy guidance, a custom needle-balloon system was positioned in the target CBD via a transcholecystic access. T1-weighted MRI was used to localize and reposition the needle-balloon system in the target. A 0.5 mL mixture of motexafin gadolinium (MGd) and trypan blue dye as well as 5-fluorouracil was delivered into the CBD wall through the needle-balloon system. Post-infusion T1-weighted MRI was obtained and contrast-to-noise ratios (CNRs) of CBD walls of pre- and post-MGd-blue infusions were compared by a paired t-test. In addition, post-infusion x-ray cholangiography was achieved to evaluate the potential injuries of CBDs by the needle-balloon system. Subsequent histologic analysis was performed to correlate and confirm the imaging findings. A post-infusion cholangiogram did not show any extravasation of contrast agent, indicating no procedure-related damage to the CBDs. MRI demonstrated clear enhancement of the target bile duct walls infused with MGd-trypan blue dye with average penetration depth of 4.7 ± 1.2 mm and an average MGd perfusion length of 21 ± 1.5 mm in the bile ducts and their surrounding tissues. The average CNR of the post-infusion bile ducts was significant higher than that of the pre-infusion bile ducts (110.6 ± 22 versus 5.7 ± 2.8, p < 0.0001). Histology depicted the blue dye staining and red fluorescence of MGd through the target CBD walls, which was well correlated with the imaging findings. It is feasible to use the new MR-compatible, needle-integrated balloon catheter system for intrabiliary

  16. Imaging of hemorrhagic fever with renal syndrome: a potential bioterrorism agent of military significance.

    PubMed

    Bui-Mansfield, Liem T; Cressler, Dana K

    2011-11-01

    Hemorrhagic fever with renal syndrome (HFRS) is a potentially fatal infectious disease with worldwide distribution. Its etiologic agents are viruses of the genus Hantavirus of the virus family Bunyaviridae. Hypothetical ease of production and distribution of these agents, with their propensity to incapacitate victims and overwhelm health care resources, lend themselves as significant potential biological agents of terrorism. HFRS has protean clinical manifestations, which may mimic upper respiratory tract infection, nephrolithiasis, and Hantavirus pulmonary syndrome and may delay proper treatment. Sequelae of HFRS, such as hemorrhage, acute renal failure, retroperitoneal edema, pancreatitis, pulmonary edema, and neurologic symptoms, can be detected by different imaging modalities. Medical providers caring for HFRS patients must be aware of its radiologic features, which may help to confirm its clinical diagnosis. In this article, the authors review the epidemiology, pathophysiology, clinical presentation, diagnosis, treatment, and complications of HFRS.

  17. Delivery of selective agents via time-delayed release tablets improves recovery of Listeria monocytogenes injured by acid and nitrite.

    PubMed

    Nyarko, Esmond; D'Amico, Dennis; Mach, Patrick; Xia, Wensheng; Donnelly, Catherine

    2014-05-01

    milk. Delivery of selective agents via time-delayed release tablets into mLRB maximizes recovery of acid- and nitrite-injured Listeria and saves analyst time during food sample analysis.

  18. Production of RS4 from rice starch and its utilization as an encapsulating agent for targeted delivery of probiotics.

    PubMed

    Ashwar, Bilal Ahmad; Gani, Asir; Gani, Adil; Shah, Asima; Masoodi, Farooq Ahmad

    2018-01-15

    The research reported in this article is based on the hypothesis that crosslinking of starch can make it a potential wall material for targeted delivery of probiotics by altering its digestion. Three probiotic strains namely Lactobacillus casei, Lactobacillus brevis and Lactobacillus plantarum were microencapsulated with resistant starch. Encapsulation yield (%) of resistant starch microspheres was in the range of 43.01-48.46. The average diameter of resistant starch microparticles was in the range of 45.53-49.29μm. Fourier transform infrared (FT-IR) spectroscopy of microcapsules showed peaks in the region of 900-1300cm(-1) and 2918-2925cm(-1) which corresponds to the presence of bacteria. Differential Scanning Calorimeter (DSC) showed better thermal stability of resistant starch microcapsules. Microencapsulated probiotics survived well in simulated gastrointestinal conditions and adverse heat conditions. The viability of the microcapsulated lactobacilli also remained high (>7 log cfu g(-1)) for 2months at 4°C. The results revealed that resistant starch is the potential new delivery carrier for oral administration of probiotics. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Boronophenylalanine, a boron delivery agent for boron neutron capture therapy, is transported by ATB0,+, LAT1 and LAT2.

    PubMed

    Wongthai, Printip; Hagiwara, Kohei; Miyoshi, Yurika; Wiriyasermkul, Pattama; Wei, Ling; Ohgaki, Ryuichi; Kato, Itsuro; Hamase, Kenji; Nagamori, Shushi; Kanai, Yoshikatsu

    2015-03-01

    The efficacy of boron neutron capture therapy relies on the selective delivery of boron carriers to malignant cells. p-Boronophenylalanine (BPA), a boron delivery agent, has been proposed to be localized to cells through transporter-mediated mechanisms. In this study, we screened aromatic amino acid transporters to identify BPA transporters. Human aromatic amino acid transporters were functionally expressed in Xenopus oocytes and examined for BPA uptake and kinetic parameters. The roles of the transporters in BPA uptake were characterized in cancer cell lines. For the quantitative assessment of BPA uptake, HPLC was used throughout the study. Among aromatic amino acid transporters, ATB(0,+), LAT1 and LAT2 were found to transport BPA with Km values of 137.4 ± 11.7, 20.3 ± 0.8 and 88.3 ± 5.6 μM, respectively. Uptake experiments in cancer cell lines revealed that the LAT1 protein amount was the major determinant of BPA uptake at 100 μM, whereas the contribution of ATB(0,+) became significant at 1000 μM, accounting for 20-25% of the total BPA uptake in MCF-7 breast cancer cells. ATB(0,+), LAT1 and LAT2 transport BPA at affinities comparable with their endogenous substrates, suggesting that they could mediate effective BPA uptake in vivo. The high and low affinities of LAT1 and ATB(0,+), respectively, differentiate their roles in BPA uptake. ATB(0,+), as well as LAT1, could contribute significantly to the tumor accumulation of BPA at clinical dose.

  20. Potential biological control agents for management of cogongrass (Cyperales: Poaceae) in the southeastern USA

    USDA-ARS?s Scientific Manuscript database

    Cogongrass, Imperata cylindrica (L.) Palisot de Beauvois (Cyperales: Poaceae), is a noxious invasive weed in the southeastern USA. Surveys for potential biological control agents of cogongrass were conducted in Asia and East Africa from 2013 to 2016. Several insect herbivores were found that may hav...

  1. Biology and preliminary host range assessment of two potential kudzu biological control agents

    Treesearch

    Matthew J. Fyre; Judith Hough-Goldstein; Jiang-Hua Sun

    2007-01-01

    Two insect species from China, Gonioctena tredecimmaclliata (Jacoby) (Coleoptera: Chrysomelidae) and Ornatalcides (Mesalcidodes) trifidus (Pascoe) (Coleoptera: Curculionidae), were studied in quarantine in the United States as potential biological control agents for kudzu, Pueraria nwntana variety Zobata (Willd.) Maesen and S. Almeida...

  2. In vitro and In vivo Studies on Stilbene Analogs as Potential Treatment Agents for Colon Cancer

    USDA-ARS?s Scientific Manuscript database

    Based upon the potential of resveratrol as a cancer chemopreventive agent, 27 stilbenes analogs were synthesized and tested against colon cancer cell line HT-29. Among these compounds, amino derivative (Z)-4-(3,5-dimethoxystyryl) aniline (4), (Z)-methyl 4-(3,5-dimethoxystyryl) benzoate (6) and (Z)-1...

  3. Biology of Leptoypha hospita (Hemiptera: Tingidae), a Potential Biological Control Agent of Chinese Privet

    Treesearch

    Yanzhuo Zhang; James L. Hanula; Scott Horn; Kristine Braman; Jianghua Sun

    2011-01-01

    The biology of Leptoypha hospita Drake et Poor (Hemiptera: Tingidae), a potential biological control agent from China for Chinese privet, Ligustrum sinense Lour., was studied in quarantine in the United States. Both nymphs and adults feed on Chinese privet mesophyll cells that lead to a bleached appearance of leaves and dieback of branch tips. L. hospita has five...

  4. Complete Genome Sequence of Ralstonia solanacearum FJAT-1458, a Potential Biocontrol Agent for Tomato Wilt

    PubMed Central

    Chen, Deju; Zhu, Yujing; Wang, Jieping; Chen, Zheng; Che, Jiamei; Zheng, Xuefang; Chen, Xiaoqiang

    2017-01-01

    ABSTRACT An avirulent strain of Ralstonia solanacearum FJAT-1458 was isolated from a living tomato. Here, we report the complete R. solanacearum FJAT-1458 genome sequence of 6,059,899 bp and 5,241 genes. This bacterial strain is a potential candidate as a biocontrol agent in the form of a plant vaccine for bacterial wilt. PMID:28385834

  5. Amorphous calcium phosphate nanoparticles could function as a novel cancer therapeutic agent by employing a suitable targeted drug delivery platform

    NASA Astrophysics Data System (ADS)

    Pourbaghi-Masouleh, Milad; Hosseini, Vahid

    2013-10-01

    Employment of nanovehicular system for delivering apoptogenic agent to cancer cells for inducing apoptosis has widely been investigated. Loading efficacy and controlled release of the agents are of the inseparable obstacles that hamper the efforts in reaching an efficacious targeted cancer therapy method. When the carrier itself is apoptogenic, then there is no need to load the carrier with apoptogenic agent and just delivering of the particle to the specific location matters. Hence, we hypothesize that amorphous calcium phosphate nanoparticle (ACPN) is a potent candidate for apoptosis induction, although encapsulation in liposome shell, and surface decoration with targeting ligand (TL), and cell-penetrating peptide (CPP) plays a pivotal role in the employment of this agent. It is well understood that elevation in cytosolic Ca2+ ([Ca2+]c) would result in the induction of apoptosis. ACPN has the potential to cause imbalance in this medium by elevating [Ca2+]c. Owning to the fact that the nanoparticles should be delivered into cytosol, it is necessary to trap them in a liposomal shell for evading endocytosis. It was demonstrated that employment of the trans-activator of transcription (TAT) as CPP eminently enhances the efficacy of endosomal escape; therefore, the platform is designed in a way that TAT is positioned on the surface of the liposome. Due to the fact that the apoptosis should be induced in sole cancer cells, Folate as TL is also attached on the surface of the liposome. This hypothesis heralds the new generation of chemotherapeutic agents and platforms which could have less side effect than the most common ones, in addition to other advantages they have.

  6. Amorphous calcium phosphate nanoparticles could function as a novel cancer therapeutic agent by employing a suitable targeted drug delivery platform.

    PubMed

    Pourbaghi-Masouleh, Milad; Hosseini, Vahid

    2013-10-30

    Employment of nanovehicular system for delivering apoptogenic agent to cancer cells for inducing apoptosis has widely been investigated. Loading efficacy and controlled release of the agents are of the inseparable obstacles that hamper the efforts in reaching an efficacious targeted cancer therapy method. When the carrier itself is apoptogenic, then there is no need to load the carrier with apoptogenic agent and just delivering of the particle to the specific location matters. Hence, we hypothesize that amorphous calcium phosphate nanoparticle (ACPN) is a potent candidate for apoptosis induction, although encapsulation in liposome shell, and surface decoration with targeting ligand (TL), and cell-penetrating peptide (CPP) plays a pivotal role in the employment of this agent. It is well understood that elevation in cytosolic Ca2+ ([Ca2+]c) would result in the induction of apoptosis. ACPN has the potential to cause imbalance in this medium by elevating [Ca2+]c. Owning to the fact that the nanoparticles should be delivered into cytosol, it is necessary to trap them in a liposomal shell for evading endocytosis. It was demonstrated that employment of the trans-activator of transcription (TAT) as CPP eminently enhances the efficacy of endosomal escape; therefore, the platform is designed in a way that TAT is positioned on the surface of the liposome. Due to the fact that the apoptosis should be induced in sole cancer cells, Folate as TL is also attached on the surface of the liposome. This hypothesis heralds the new generation of chemotherapeutic agents and platforms which could have less side effect than the most common ones, in addition to other advantages they have.

  7. Zinc Oxide Nanoparticles for Selective Destruction of Tumor Cells and Potential for Drug Delivery Applications

    PubMed Central

    Rasmussen, John W.; Martinez, Ezequiel; Louka, Panagiota; Wingett, Denise G.

    2010-01-01

    Importance of the field Metal oxide nanoparticles, including zinc oxide, are versatile platforms for biomedical applications and therapeutic intervention. There is an urgent need to develop new classes of anticancer agents, and recent studies demonstrate that ZnO nanomaterials hold considerable promise. Areas covered in this review This review analyzes the biomedical applications of metal oxide and ZnO nanomaterials under development at the experimental, preclinical, and clinical levels. A discussion regarding the advantages, approaches, and limitations surrounding the use of metal oxide nanoparticles for cancer applications and drug delivery is presented. The scope of this article is focused on ZnO, and other metal oxide nanomaterial systems, and their proposed mechanisms of cytotoxic action, as well as current approaches to improve their targeting and cytotoxicity against cancer cells. Take home message Through a better understanding of the mechanisms of action and cellular consequences resulting from nanoparticles interactions with cells, the inherent toxicity and selectivity of ZnO nanoparticles against cancer may be further improved to make them attractive new anti-cancer agents. PMID:20716019

  8. Cysteamine-related agents could be potential antidepressants through increasing central BDNF levels.

    PubMed

    Tsai, Shih-Jen

    2006-01-01

    Major depressive disorder (MDD) is a common mental disease, but with an unknown etiology. Antidepressants are the main biological treatment for MDD. However, current antidepressive agents have a slow onset of effect and a substantial proportion of MDD patients do not clinically improve, despite maximal medication. Thus, the exploration for new antidepressants with novel strategies may help to develop faster and more effective antidepressant agents. Studies in the recent decades have demonstrated that antidepressants increase central brain-derived neurotrophic factor (BDNF) levels and activating the BDNF-signaling pathway may play an important role in their therapeutic mechanism. Cysteamine is a natural product of cells and constitutes the terminal region of the CoA molecule. Recent work has found that cysteamine and a related agent, cystamine, have neuroprotective effects in Huntington's disease (HD) mice, through enhancing central BDNF levels. Furthermore, cystamine or cysteamine injection could increase serum BDNF levels in wild-type mice as well as HD mice. Since activation of the BDNF-dependent pathway plays an important role in the mechanism of antidepressant therapeutic action, cystamine or its derivatives could have potential antidepressant therapeutic effects. Among these agents, pantethine may be one of the most promising agents. It is a naturally occurring compound which can be administered orally with negligible side effects, and is metabolized to cysteamine. Further evaluation of the therapeutic and toxic effects of these cysteamine-related antidepressant agents in MDD animal models is needed before any clinical application.

  9. A Review of the Disruptive Potential of Botulinum Neurotoxins as Chemical Warfare Agents

    DTIC Science & Technology

    2011-10-01

    SUBJECT TERMS Botulinum neurotoxin, national security, chemical agents, chemical warfare, force health protection 16. SECURITY CLASSIFICATION OF: 17...the local health -care infrastructure. For anybody trained in epidemiology and crisis management, this presents a “devil’s brew” of potential...mortality rates, the potential for major public health impact, the ability to cause public panic and social disruption, and the requirement for special

  10. The potential of theragnostic 124I-8H9 convection-enhanced delivery in diffuse intrinsic pontine glioma

    PubMed Central

    Luther, Neal; Zhou, Zhiping; Zanzonico, Pat; Cheung, Nai-Kong; Humm, John; Edgar, Mark A.; Souweidane, Mark M.

    2014-01-01

    Background Reasons for failure in prior human glioma convection-enhanced delivery (CED) clinical trials remain unclear. Concentration-dependent volume of distribution (Vd) measurement of CED-infused agents in the human brain is challenging and highlights a potential technical shortcoming. Activity of iodine isotope 124 (124I ) in tissue can be directly measured in vivo with high resolution via PET. With the potential therapeutic utility of radioimmunotherapy, we postulate 124I conjugated to the antiglioma monoclonal antibody 8H9 may serve as a “theragnostic” agent delivered via CED to diffuse intrinsic pontine glioma. Methods Fifteen rats underwent CED of 0.1–1.0 mCi of 131I-8H9 to the pons for toxicity evaluation. Six additional rats underwent CED of 10 µCi of 124I-8H9 to the pons for dosimetry, with serial microPET performed for 1 week. Two primates underwent CED of gadolinium-albumin and 1.0 mCi of 124I-8H9 to the pons for safety and dosimetry analysis. Serial postoperative PET, blood, and CSF radioactivity counts were performed. Results One rat (1.0 mCi 131I-8H9 infusion) suffered toxicity necessitating early sacrifice. PET analysis in rats yielded a pontine absorbed dose of 37 Gy/mCi. In primates, no toxicity was observed, and absorbed pontine dose was 3.8 Gy/mCi. Activity decreased 10-fold with 48 h following CED in both animal models. Mean Vd was 0.14 cc3 (volume of infusion [Vi] to Vd ratio = 14) in the rat and 6.2 cc3 (Vd/Vi = 9.5) in primate. Conclusion The safety and feasibility of 124I dosimetry following CED via PET is demonstrated, establishing a preclinical framework for a trial evaluating CED of 124I-8H9 for diffuse intrinsic pontine glioma. PMID:24526309

  11. Intelligent Agents and Their Potential for Future Design and Synthesis Environment

    NASA Technical Reports Server (NTRS)

    Noor, Ahmed K. (Compiler); Malone, John B. (Compiler)

    1999-01-01

    This document contains the proceedings of the Workshop on Intelligent Agents and Their Potential for Future Design and Synthesis Environment, held at NASA Langley Research Center, Hampton, VA, September 16-17, 1998. The workshop was jointly sponsored by the University of Virginia's Center for Advanced Computational Technology and NASA. Workshop attendees came from NASA, industry and universities. The objectives of the workshop were to assess the status of intelligent agents technology and to identify the potential of software agents for use in future design and synthesis environment. The presentations covered the current status of agent technology and several applications of intelligent software agents. Certain materials and products are identified in this publication in order to specify adequately the materials and products that were investigated in the research effort. In no case does such identification imply recommendation or endorsement of products by NASA, nor does it imply that the materials and products are the only ones or the best ones available for this purpose. In many cases equivalent materials and products are available and would probably produce equivalent results.

  12. Molecular effective coverage surface area of optical clearing agents for predicting optical clearing potential

    NASA Astrophysics Data System (ADS)

    Feng, Wei; Ma, Ning; Zhu, Dan

    2015-03-01

    The improvement of methods for optical clearing agent prediction exerts an important impact on tissue optical clearing technique. The molecular dynamic simulation is one of the most convincing and simplest approaches to predict the optical clearing potential of agents by analyzing the hydrogen bonds, hydrogen bridges and hydrogen bridges type forming between agents and collagen. However, the above analysis methods still suffer from some problem such as analysis of cyclic molecule by reason of molecular conformation. In this study, a molecular effective coverage surface area based on the molecular dynamic simulation was proposed to predict the potential of optical clearing agents. Several typical cyclic molecules, fructose, glucose and chain molecules, sorbitol, xylitol were analyzed by calculating their molecular effective coverage surface area, hydrogen bonds, hydrogen bridges and hydrogen bridges type, respectively. In order to verify this analysis methods, in vitro skin samples optical clearing efficacy were measured after 25 min immersing in the solutions, fructose, glucose, sorbitol and xylitol at concentration of 3.5 M using 1951 USAF resolution test target. The experimental results show accordance with prediction of molecular effective coverage surface area. Further to compare molecular effective coverage surface area with other parameters, it can show that molecular effective coverage surface area has a better performance in predicting OCP of agents.

  13. Investigating the potential of employing bilosomes as a novel vesicular carrier for transdermal delivery of tenoxicam.

    PubMed

    Al-Mahallawi, Abdulaziz M; Abdelbary, Aly A; Aburahma, Mona H

    2015-05-15

    Bilosomes represent an evolving vesicular carrier that have been explored for oral vaccines delivery based on its ability to resist enzymes and bile salts in the gastrointestinal tract (GIT). Bilosomes vesicles are formed of bilayer membrane of non-ionic surfactant molecules encompassing bile salts. Although, bilosomes have not been proposed for transdermal drug delivery, this carrier seems to have promising potential in this regard. Accordingly, the aim of this investigation was to assess the capability and safety of utilizing bilosomes for transdermal delivery of tenoxicam (TX) as a model drug. A 3(1)2(2) full factorial design was adopted to study the effects of different formulation parameters on bilosomes properties and select the optimal formulation using Design-Expert(®) software. The selected formulation displayed nano-sized spherical vesicles (242.5 ± 6.43nm) with reasonable entrapment efficiency percent (68.33 ± 2.33%). Confocal laser scanning microscopy confirmed the capability of the flourolabeled bilosomes to penetrate deep within the skin. Both, ex vivo permeation and in vivo skin deposition studies confirmed the superiority of bilosomes over drug solution in delivering TX transdermally. In addition, in vivo histopathological study proved the safety of topically applied bilosomes. In summary, the highlighted results confirmed that bilosomes can be further adopted for delivering drugs transdermally.

  14. Investigation into the potential of low-frequency ultrasound facilitated topical delivery of Cyclosporin A.

    PubMed

    Liu, Hongzhuo; Li, Sanming; Pan, Weisan; Wang, Yongjun; Han, Fei; Yao, Huimin

    2006-12-01

    The potential for low-frequency ultrasound facilitated topical transport of Cyclosporin A was investigated using rat skin. Studies of intensity and exposure time acting on the deposition of Cyclosporin A into deeper skin of in vitro sonophoresis were performed. Low-frequency ultrasound increased the amount of Cyclosporin A retained in the skin only seven times than the passive diffusion. Furthermore, we also tested the synergistic effect of ultrasound and other approaches such as chemical enhancers and electroporation on topical drug delivery of Cyclosporin A. We found that the efficacy of low-frequency ultrasound in enhancing topical delivery could be further increased by pretreatment of skin with chemical enhancers, such as laurocapram (Azone) and sodium lauryl sulfate (SLS). Meanwhile only a small amount was seen to across the full skin into the receiver compartment. Trimodality treatment comprising of pretreatment with Azone+ultrasound in combination followed by electroporation was not effective in enhancing the topical delivery of Cyclosporin A. However, this combination strategy increased the penetration of Cyclosporin A through rat skin by order of 15. The histopathological findings revealed that there was almost no change observed in the structure of skin after ultrasound or combination with ultrasound and enhancers as compared with the control group. In general, the enhanced skin accumulation of Cyclosporin A by the combination of low-frequency ultrasound and chemical enhancers could help significantly to optimize the targeting of the drug without of a concomitant increase of the systemic side effects.

  15. Convection-enhanced drug delivery to the brain: therapeutic potential and neuropathological considerations.

    PubMed

    Barua, Neil U; Gill, Steven S; Love, Seth

    2014-03-01

    Convection-enhanced delivery (CED) describes a direct method of drug delivery to the brain through intraparenchymal microcatheters. By establishing a pressure gradient at the tip of the infusion catheter in order to exploit bulk flow through the interstitial spaces of the brain, CED offers a number of advantages over conventional drug delivery methods-bypass of the blood-brain barrier, targeted distribution through large brain volumes and minimization of systemic side effects. Despite showing early promise, CED is yet to fulfill its potential as a mainstream strategy for the treatment of neurological disease. Substantial research effort has been dedicated to optimize the technology for CED and identify the parameters, which govern successful drug distribution. It seems likely that successful clinical translation of CED will depend on suitable catheter technology being used in combination with drugs with optimal physicochemical characteristics, and on neuropathological analysis in appropriate preclinical models. In this review, we consider the factors most likely to influence the success or failure of CED, and review its application to the treatment of high-grade glioma, Parkinson's disease (PD) and Alzheimer's disease (AD).

  16. Invited review: Milk phospholipid vesicles, their colloidal properties, and potential as delivery vehicles for bioactive molecules.

    PubMed

    Arranz, E; Corredig, M

    2017-06-01

    The milk fat globule membrane (MFGM) is a unique colloidal assembly of phospholipids and proteins, with numerous potential applications as functional ingredient. The phospholipid components of the MFGM are gaining interest as they are a useful matrix for use as a constituent of delivery systems such as liposomes. Liposomes formulated with milk phospholipids are becoming an alternative to other sources of phospholipids such as soybean or egg yolk. However, incorporation of phospholipids fractionated from the milk fat globule membrane in dairy products requires an in-depth understanding of the functional properties of phospholipids. In particular, it is critical to understand which factors play a role in their stability and bioefficacy as delivery systems. Moreover, chemical and physical modifications of phospholipid liposomes occurring during digestion and the fate of the encapsulated compounds are very important to understand. This review discusses recent findings on the structure and functionality of MFGM, the bioactivity of the phospholipids fraction, their utilization as delivery systems, and their stability through gastrointestinal transit. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  17. Porous metal-organic-framework nanoscale carriers as a potential platform for drug delivery and imaging

    NASA Astrophysics Data System (ADS)

    Horcajada, Patricia; Chalati, Tamim; Serre, Christian; Gillet, Brigitte; Sebrie, Catherine; Baati, Tarek; Eubank, Jarrod F.; Heurtaux, Daniela; Clayette, Pascal; Kreuz, Christine; Chang, Jong-San; Hwang, Young Kyu; Marsaud, Veronique; Bories, Phuong-Nhi; Cynober, Luc; Gil, Sophie; Férey, Gérard; Couvreur, Patrick; Gref, Ruxandra

    2010-02-01

    In the domain of health, one important challenge is the efficient delivery of drugs in the body using non-toxic nanocarriers. Most of the existing carrier materials show poor drug loading (usually less than 5wt% of the transported drug versus the carrier material) and/or rapid release of the proportion of the drug that is simply adsorbed (or anchored) at the external surface of the nanocarrier. In this context, porous hybrid solids, with the ability to tune their structures and porosities for better drug interactions and high loadings, are well suited to serve as nanocarriers for delivery and imaging applications. Here we show that specific non-toxic porous iron(III)-based metal-organic frameworks with engineered cores and surfaces, as well as imaging properties, function as superior nanocarriers for efficient controlled delivery of challenging antitumoural and retroviral drugs (that is, busulfan, azidothymidine triphosphate, doxorubicin or cidofovir) against cancer and AIDS. In addition to their high loadings, they also potentially associate therapeutics and diagnostics, thus opening the way for theranostics, or personalized patient treatments.

  18. Targeting activated microglia in Alzheimer's pathology by intraventricular delivery of a phagocytosable MRI contrast agent in APP23 transgenic mice.

    PubMed

    Mundt, Adrian P; Winter, Christine; Mueller, Susanne; Wuerfel, Jens; Tysiak, Eva; Schnorr, Jörg; Taupitz, Matthias; Heinz, Andreas; Juckel, Georg

    2009-06-01

    The role of phagocytosing immune cells in Alzheimer's pathology can be studied experimentally in APP23 transgenic mice. This present study intended to label phagocytosing immune cells in the plaque periphery of APP23 mice in vivo by intraventricular injection of VSOP-C184, a phagocytosable iron oxide nanoparticle MRI contrast agent. Firstly, the dosages of 0.1, 1.0 and 10 micromol Fe/kg body weight dissolved in 500 nl of artificial cerebrospinal fluid, delivered by stereotaxic surgery were evaluated 4 h after surgery in 7 wild type mice using 7 T MRI. Secondly, the dosage of 1.0 micromol Fe/kg body weight was investigated in 6 APP23 mice. The distribution of iron oxide particles was evaluated histologically. The injection of 0.1 micromol Fe/kg body weight did not result in any signal alterations, 10 micromol resulted in strong signal artifacts. The delivery of 1.0 micromol Fe/kg body weight in wild type mice resulted in MRI signal alterations throughout the ventricular system without large artifacts. It was regarded superior to other dosages for the study of the transgenic mice. There was no difference in MRI signal alterations and the distribution of iron particles in the histology between APP23 and wild type mice using the dosage of 1.0 micromol Fe/kg body weight. Upon intraventricular injection, the phagocytosable contrast agent VSOP-C184 distributes throughout the ventricular system, whereas it does not reach the periphery of amyloid plaques in APP23 mice in a concentration sufficient to cause MRI signal alterations.

  19. Development of microencapsulation delivery system for long-term preservation of probiotics as biotherapeutics agent.

    PubMed

    Solanki, Himanshu K; Pawar, Dipak D; Shah, Dushyant A; Prajapati, Vipul D; Jani, Girish K; Mulla, Akil M; Thakar, Prachi M

    2013-01-01

    The administration of probiotic bacteria for health benefit has rapidly expanded in recent years, with a global market worth $32.6 billion predicted by 2014. The oral administration of most of the probiotics results in the lack of ability to survive in a high proportion of the harsh conditions of acidity and bile concentration commonly encountered in the gastrointestinal tract of humans. Providing probiotic living cells with a physical barrier against adverse environmental conditions is therefore an approach currently receiving considerable interest. Probiotic encapsulation technology has the potential to protect microorganisms and to deliver them into the gut. However, there are still many challenges to overcome with respect to the microencapsulation process and the conditions prevailing in the gut. This review focuses mainly on the methodological approach of probiotic encapsulation including biomaterials selection and choice of appropriate technology in detailed manner.

  20. Development of Microencapsulation Delivery System for Long-Term Preservation of Probiotics as Biotherapeutics Agent

    PubMed Central

    Solanki, Himanshu K.; Pawar, Dipak D.; Shah, Dushyant A.; Prajapati, Vipul D.; Jani, Girish K.; Mulla, Akil M.; Thakar, Prachi M.

    2013-01-01

    The administration of probiotic bacteria for health benefit has rapidly expanded in recent years, with a global market worth $32.6 billion predicted by 2014. The oral administration of most of the probiotics results in the lack of ability to survive in a high proportion of the harsh conditions of acidity and bile concentration commonly encountered in the gastrointestinal tract of humans. Providing probiotic living cells with a physical barrier against adverse environmental conditions is therefore an approach currently receiving considerable interest. Probiotic encapsulation technology has the potential to protect microorganisms and to deliver them into the gut. However, there are still many challenges to overcome with respect to the microencapsulation process and the conditions prevailing in the gut. This review focuses mainly on the methodological approach of probiotic encapsulation including biomaterials selection and choice of appropriate technology in detailed manner. PMID:24027760

  1. The Potential of Streptomyces as Biocontrol Agents against the Rice Blast Fungus, Magnaporthe oryzae (Pyricularia oryzae)

    PubMed Central

    Law, Jodi Woan-Fei; Ser, Hooi-Leng; Khan, Tahir M.; Chuah, Lay-Hong; Pusparajah, Priyia; Chan, Kok-Gan; Goh, Bey-Hing; Lee, Learn-Han

    2017-01-01

    Rice is a staple food source for more than three billion people worldwide. However, rice is vulnerable to diseases, the most destructive among them being rice blast, which is caused by the fungus Magnaporthe oryzae (anamorph Pyricularia oryzae). This fungus attacks rice plants at all stages of development, causing annual losses of approximately 10–30% in various rice producing regions. Synthetic fungicides are often able to effectively control plant diseases, but some fungicides result in serious environmental and health problems. Therefore, there is growing interest in discovering and developing new, improved fungicides based on natural products as well as introducing alternative measures such as biocontrol agents to manage plant diseases. Streptomyces bacteria appear to be promising biocontrol agents against a wide range of phytopathogenic fungi, which is not surprising given their ability to produce various bioactive compounds. This review provides insight into the biocontrol potential of Streptomyces against the rice blast fungus, M. oryzae. The ability of various Streptomyces spp. to act as biocontrol agents of rice blast disease has been studied by researchers under both laboratory and greenhouse/growth chamber conditions. Laboratory studies have shown that Streptomyces exhibit inhibitory activity against M. oryzae. In greenhouse studies, infected rice seedlings treated with Streptomyces resulted in up to 88.3% disease reduction of rice blast. Studies clearly show that Streptomyces spp. have the potential to be used as highly effective biocontrol agents against rice blast disease; however, the efficacy of any biocontrol agent may be affected by several factors including environmental conditions and methods of application. In order to fully exploit their potential, further studies on the isolation, formulation and application methods of Streptomyces along with field experiments are required to establish them as effective biocontrol agents. PMID:28144236

  2. The Potential of Streptomyces as Biocontrol Agents against the Rice Blast Fungus, Magnaporthe oryzae (Pyricularia oryzae).

    PubMed

    Law, Jodi Woan-Fei; Ser, Hooi-Leng; Khan, Tahir M; Chuah, Lay-Hong; Pusparajah, Priyia; Chan, Kok-Gan; Goh, Bey-Hing; Lee, Learn-Han

    2017-01-01

    Rice is a staple food source for more than three billion people worldwide. However, rice is vulnerable to diseases, the most destructive among them being rice blast, which is caused by the fungus Magnaporthe oryzae (anamorph Pyricularia oryzae). This fungus attacks rice plants at all stages of development, causing annual losses of approximately 10-30% in various rice producing regions. Synthetic fungicides are often able to effectively control plant diseases, but some fungicides result in serious environmental and health problems. Therefore, there is growing interest in discovering and developing new, improved fungicides based on natural products as well as introducing alternative measures such as biocontrol agents to manage plant diseases. Streptomyces bacteria appear to be promising biocontrol agents against a wide range of phytopathogenic fungi, which is not surprising given their ability to produce various bioactive compounds. This review provides insight into the biocontrol potential of Streptomyces against the rice blast fungus, M. oryzae. The ability of various Streptomyces spp. to act as biocontrol agents of rice blast disease has been studied by researchers under both laboratory and greenhouse/growth chamber conditions. Laboratory studies have shown that Streptomyces exhibit inhibitory activity against M. oryzae. In greenhouse studies, infected rice seedlings treated with Streptomyces resulted in up to 88.3% disease reduction of rice blast. Studies clearly show that Streptomyces spp. have the potential to be used as highly effective biocontrol agents against rice blast disease; however, the efficacy of any biocontrol agent may be affected by several factors including environmental conditions and methods of application. In order to fully exploit their potential, further studies on the isolation, formulation and application methods of Streptomyces along with field experiments are required to establish them as effective biocontrol agents.

  3. Evaluation of potential of Zn-pectinate gel (ZPG) microparticles containing mesalazine for colonic drug delivery

    PubMed Central

    Kawadkar, J.; Chauhan Meenakshi, K.; Ram, A.

    2010-01-01

    Background and the purpose of the study Pectin derivatives have been utilized for colonic drug delivery (CDD). In this study the effects of different formulation variables upon the characteristics of pectinate microparticles (MPs) prepared by ionotropic gelation technique for colonic delivery of mesalazine was investigated. Methods In-vitro drug release of MPs was studied using USP XXIV dissolution apparatus type I, in different fluids e.g. simulated gastric fluid (SGF: pH 1.2), simulated intestinal fluid (SIF: pH 7.4), and simulated colonic fluid (SCF: pH 6.8) of volume 900 ml, at 100 rpm maintained at 37±0.2°C. This study was also performed in the presence of 4% w/v rat caecal content (RCC) using phosphate buffer saline (pH 6.8) as SCF. Gamma scintigraphy study was performed on New Zealand rabbit animal model using 99m Tc. Results The results showed that maximum entrapment of mesalazine (86.1±1.7%) and strength of gel network zinc pectinate gel microparticles (ZPGD2) was achieved in cross-linking solution of pH 1.6. Batch of ZPGD2 showed least swelling ratio and drug release. In RCC medium the t50% value of CPG-MPs was 3–4 folds greater than ZPG-MPs. Scintigram showed the residence of ZPG-MPs (filled in enteric coated capsule) in colon more than 9 hrs and delivery of almost all the drug loading dose in colon. Major conclusion The results of this study suggest the designed formulation of ZPG-MPs has the potential to serve as a colonic drug delivery system. PMID:22615619

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

    PubMed

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

    2010-03-01

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

  5. The potential of pectin as a stabilizer for liposomal drug delivery systems.

    PubMed

    Smistad, Gro; Bøyum, Silje; Alund, Siv Jorunn; Samuelsen, Anne Berit C; Hiorth, Marianne

    2012-10-15

    The aim of the present study was to investigate the potential of different types of pectin as stabilizers for liposomal drug delivery systems. Positively charged liposomes were coated with commercially available and purified low-methoxylated (LM), high-methoxylated (HM) and amidated (AM) pectins. The samples were stored for up to 12 weeks at 4°C, at room temperature and at 35°C. The change in liposomal size and size distribution, zeta potential, pH, leakage of encapsulated carboxyfluorescein (CF), and lipid degradation were studied. All the types of pectin were found to protect the liposomes against aggregation during storage. The pectin coat did not affect the permeability of the liposome membrane. HM and LM pectin seemed to be the most promising types of pectin due to minimal changes in the zeta potentials during storage for these samples and no detectable lipid degradation. It is concluded that pectin may be used for stabilizing liposomal drug delivery systems. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Rapid, Cell-Based Toxicity Screen of Potentially Therapeutic Post-Transcriptional Gene Silencing Agents

    PubMed Central

    Kolniak, Tiffany A.; Sullivan, Jack M.

    2011-01-01

    Post-transcriptional gene silencing (PTGS) agents such as antisense, ribozymes and RNA interference (RNAi) have great potential as therapeutics for a variety of eye diseases including retinal and macular degenerations, glaucoma, corneal degenerations, inflammatory and viral conditions. Despite their great potential and over thirty years of academic and corporate research only a single PTGS agent is currently approved for human therapy for a single disease. Substantial challenges exist to achieving both efficacious and safe PTGS agents. Efficacy, as measured in specific target mRNA and protein knockdown, depends upon a number of complex factors including the identification of rare regions of target mRNA accessibility, cellular colocalization of the PTGS agent in sufficient concentration with the target mRNA, and stability of the PTGS agent in the target cells in which it is delivered or expressed. Safety is commonly measured by lack of cytotoxicity or other deleterious cellular responses in cells in which the PTGS agent is delivered or expressed. To relieve major bottlenecks in RNA drug discovery novel, efficient, inexpensive, and rapid tools are needed to facilitate lead identification of the most efficacious PTGS agent, rational optimization of efficacy of the lead agent, and lead agent safety determinations. We have developed a technological platform using cell culture expression systems that permits lead identification and efficacy optimization of PTGS agents against arbitrary disease target mRNAs under relatively high throughput conditions. Here, we extend the technology platform to include PTGS safety determinations in cultured human cells that are expected to represent the common cellular housekeeping microenvironment. We developed a high throughput screening (HTS) cytotoxicity assay in 96-well plate format based around the SYTOX Green dye which is excluded from healthy viable cells and becomes substantially fluorescent only after entering cells and binding

  7. General guidelines for medically screening mixed population groups potentially exposed to nerve or vesicant agents

    SciTech Connect

    Watson, A.P.; Munro, N.B.; Sidell, F.R.; Leffingwell, S.S.

    1992-01-01

    A number of state and local planners have requested guidance on screening protocols and have expressed interest in sampling body fluids from exposed or potentially exposed individuals as a means of estimating agent dose. These guidelines have been developed to provide a clear statement that could be used by state and local emergency response personnel in the event of a nerve or vesicant agent incident resulting in off-post contamination; maximum protection from harm is the goal. The assumption is that any population group so exposed would be heterogeneous for age, gender, reproductive status, and state of health.

  8. General guidelines for medically screening mixed population groups potentially exposed to nerve or vesicant agents

    SciTech Connect

    Watson, A.P.; Munro, N.B. ); Sidell, F.R. ); Leffingwell, S.S. . Center for Environmental Health and Injury Control)

    1992-01-01

    A number of state and local planners have requested guidance on screening protocols and have expressed interest in sampling body fluids from exposed or potentially exposed individuals as a means of estimating agent dose. These guidelines have been developed to provide a clear statement that could be used by state and local emergency response personnel in the event of a nerve or vesicant agent incident resulting in off-post contamination; maximum protection from harm is the goal. The assumption is that any population group so exposed would be heterogeneous for age, gender, reproductive status, and state of health.

  9. The Potential Use of Pharmacological Agents to Modulate Orthodontic Tooth Movement (OTM)

    PubMed Central

    Kouskoura, Thaleia; Katsaros, Christos; von Gunten, Stephan

    2017-01-01

    The biological processes that come into play during orthodontic tooth movement (OTM) have been shown to be influenced by a variety of pharmacological agents. The effects of such agents are of particular relevance to the clinician as the rate of tooth movement can be accelerated or reduced as a result. This review aims to provide an overview of recent insights into drug-mediated effects and the potential use of drugs to influence the rate of tooth movement during orthodontic treatment. The limitations of current experimental models and the need for well-designed clinical and pre-clinical studies are also discussed. PMID:28228735

  10. Tumor growth suppression by gadolinium-neutron capture therapy using gadolinium-entrapped liposome as gadolinium delivery agent.

    PubMed

    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. Targeted Delivery of Anticancer Agents via a Dual Function Nanocarrier with an Interfacial Drug-Interactive Motif

    PubMed Central

    2015-01-01

    We have developed a dual-function drug carrier, polyethylene glycol (PEG)-derivatized farnesylthiosalicylate (FTS). Here we report that incorporation of a drug-interactive motif (Fmoc) into PEG5k–FTS2 led to further improvement in both drug loading capacity and formulation stability. Doxorubicin (DOX) formulated in PEG5k–Fmoc–FTS2 showed sustained release kinetics slower than those of DOX loaded in PEG5k–FTS2. The maximum tolerated dose of DOX- or paclitaxel (PTX)-loaded PEG5k–Fmoc–FTS2 was significantly higher than that of the free drug. Pharmacokinetics and biodistribution studies showed that DOX/PEG5k–Fmoc–FTS2 mixed micelles were able to retain DOX in the bloodstream for a significant amount of time and efficiently deliver the drug to tumor sites. More importantly, drug (DOX or PTX)-loaded PEG5k–Fmoc–FTS2 led to superior antitumor activity over other treatments including drugs formulated in PEG5k–FTS2 in breast cancer and prostate cancer models. Our improved dual function carrier with a built-in drug-interactive motif represents a simple and effective system for targeted delivery of anticancer agents. PMID:25325795

  12. Folic acid-functionalized polyethylenimine superparamagnetic iron oxide nanoparticles as theranostic agents for magnetic resonance imaging and PD-L1 siRNA delivery for gastric cancer.

    PubMed

    Luo, Xin; Peng, Xia; Hou, Jingying; Wu, Shuyun; Shen, Jun; Wang, Lingyun

    2017-01-01

    Programmed death ligand-1 (PD-L1), which is highly expressed in gastric cancers, interacts with programmed death-1 (PD-1) on T cells and is involved in T-cell immune resistance. To increase the therapeutic safety and accuracy of PD-1/PD-L1 blockade, RNA interference through targeted gene delivery was performed in our study. We developed folic acid (FA)- and disulfide (SS)-polyethylene glycol (PEG)-conjugated polyethylenimine (PEI) complexed with superparamagnetic iron oxide Fe3O4 nanoparticles (SPIONs) as a siRNA-delivery system for PD-L1 knockdown. The characterization, binding ability, cytotoxicity, transfection efficiency, and cellular internalization of the polyplex were determined. At nitrogen:phosphate (N:P) ratios of 10 or above, the FA-PEG-SS-PEI-SPIONs bound to PD-L1 siRNA to form a polyplex with a diameter of approximately 120 nm. Cell-viability assays showed that the polyplex had minimal cytotoxicity at low N:P ratios. The FA-conjugated polyplex showed higher transfection efficiency and cellular internalization in the folate receptor-overexpressing gastric cancer cell line SGC-7901 than a non-FA-conjugated polyplex. Subsequently, we adopted the targeted FA-PEG-SS-PEI-SPION/siRNA polyplexes at an N:P ratio of 10 for function studies. Cellular magnetic resonance imaging (MRI) showed that the polyplex could also act as a T2-weighted contrast agent for cancer MRI. Furthermore, one of four PD-L1 siRNAs exhibited effective PD-L1 knockdown in PD-L1-overexpressing SGC-7901. To determine the effects of the functionalized polyplex on T-cell function, we established a coculture model of activated T cells and SGC-7901 cells and demonstrated changes in secreted cytokines. Our findings highlight the potential of this class of multifunctional theranostic nanoparticles for effective targeted PD-L1-knockdown therapy and MRI diagnosis in gastric cancers.

  13. Light-responsive polymer microcapsules as delivery systems for natural active agents

    SciTech Connect

    Bizzarro, Valentina; Carfagna, Cosimo; Cerruti, Pierfrancesco; Marturano, Valentina; Ambrogi, Veronica

    2016-05-18

    In this work we report the preparation and the release behavior of UV-responsive polymeric microcapsules containing essential oils as a core. The oil acted also as a monomer solvent during polymerization. Accordingly, the potentially toxic organic solvent traditionally used was replaced with a natural active substance, resulting in a more sustainable functional system. Polymer shell was based on a lightly cross-linked polyamide containing UV-sensitive azobenzene moieties in the main chain. The micro-sized capsules were obtained via interfacial polycondensation in o/w emulsion, and their mean size was measured via Dynamic Light Scattering. Shape and morphology were analyzed through Scanning Electron and Optical Microscopy. UV-responsive behavior was evaluated via spectrofluorimetry, by assessing the release kinetics of a fluorescent probe molecule upon UV light irradiation (λ{sub max}=360 nm). The irradiated samples showed an increase in fluorescence intensity, in accordance with the increase of the probe molecule concentration in the release medium. As for the un-irradiated sample, no changes could be detected demonstrating the effectiveness of the obtained releasing system.

  14. Orally Administered Bifidobacteria as Vehicles for Delivery of Agents to Systemic Tumors

    PubMed Central

    Cronin, Michelle; Morrissey, David; Rajendran, Simon; El Mashad, Shereen M; van Sinderen, Douwe; O'Sullivan, Gerald C; Tangney, Mark

    2010-01-01

    Certain bacteria have emerged as biological gene vectors with natural tumor specificity, capable of specifically delivering genes or gene products to the tumor environment when intravenously (i.v.) administered to rodent models. We show for the first time that oral administration of bacteria to mice resulted in their translocation from the gastrointestinal tract (GIT) with subsequent homing to and replication specifically in tumors. The commensal, nonpathogenic Bifidobacterium breve UCC2003 harboring a plasmid expressing lux fed to mice bearing subcutaneous (s.c.) tumors were readily detected specifically in tumors, by live whole-body imaging, at levels similar to i.v. administration. Reporter gene expression was visible for >2 weeks in tumors. Mice remained healthy throughout experiments. Cytokine analyses indicated a significant upregulation of interferon-γ (IFN-γ) in the GIT of bifidobacteria-fed mice, which is associated with increases in epithelial permeability. However, B. breve feeding did not increase systemic levels of other commensal bacteria. The presence of tumor was not necessary for translocation to systemic organs to occur. These findings indicate potential for safe and efficient gene-based treatment and/or detection of tumors via ingestion of nonpathogenic bacteria expressing therapeutic or reporter genes. PMID:20389288

  15. Light-responsive polymer microcapsules as delivery systems for natural active agents

    NASA Astrophysics Data System (ADS)

    Bizzarro, Valentina; Carfagna, Cosimo; Cerruti, Pierfrancesco; Marturano, Valentina; Ambrogi, Veronica

    2016-05-01

    In this work we report the preparation and the release behavior of UV-responsive polymeric microcapsules containing essential oils as a core. The oil acted also as a monomer solvent during polymerization. Accordingly, the potentially toxic organic solvent traditionally used was replaced with a natural active substance, resulting in a more sustainable functional system. Polymer shell was based on a lightly cross-linked polyamide containing UV-sensitive azobenzene moieties in the main chain. The micro-sized capsules were obtained via interfacial polycondensation in o/w emulsion, and their mean size was measured via Dynamic Light Scattering. Shape and morphology were analyzed through Scanning Electron and Optical Microscopy. UV-responsive behavior was evaluated via spectrofluorimetry, by assessing the release kinetics of a fluorescent probe molecule upon UV light irradiation (λmax=360 nm). The irradiated samples showed an increase in fluorescence intensity, in accordance with the increase of the probe molecule concentration in the release medium. As for the un-irradiated sample, no changes could be detected demonstrating the effectiveness of the obtained releasing system.

  16. Live-Attenuated Bacterial Vectors: Tools for Vaccine and Therapeutic Agent Delivery

    PubMed Central

    Lin, Ivan Y. C.; Van, Thi Thu Hao; Smooker, Peter M.

    2015-01-01

    Genetically attenuated microorganisms, including pathogenic and commensal bacteria, can be engineered to carry and deliver heterologous antigens to elicit host immunity against both the vector as well as the pathogen from which the donor gene is derived. These live attenuated bacterial vectors have been given much attention due to their capacity to induce a broad range of immune responses including localized mucosal, as well as systemic humoral and/or cell-mediated immunity. In addition, the unique tumor-homing characteristics of these bacterial vectors has also been exploited for alternative anti-tumor vaccines and therapies. In such approach, tumor-associated antigen, immunostimulatory molecules, anti-tumor drugs, or nucleotides (DNA or RNA) are delivered. Different potential vectors are appropriate for specific applications, depending on their pathogenic routes. In this review, we survey and summarize the main features of the different types of live bacterial vectors and discussed the clinical applications in the field of vaccinology. In addition, different approaches for using live attenuated bacterial vectors for anti-cancer therapy is discussed, and some promising pre-clinical and clinical studies in this field are outlined. PMID:26569321

  17. Mesoporous manganese silicate coated silica nanoparticles as multi-stimuli-responsive T1-MRI contrast agents and drug delivery carriers.

    PubMed

    Li, Xiaowei; Zhao, Wenru; Liu, Xiaohang; Chen, Kaiqiang; Zhu, Shaojia; Shi, Ping; Chen, Yu; Shi, Jianlin

    2016-01-01

    A novel kind of monodisperse mesoporous manganese silicate coated silica nanoparticle (MMSSN) as a highly efficient T1-weighted MRI contrast agent (CA) and drug carrier for cancer diagnosis and chemotherapy has been constructed by a modified "SiO2 sacrifice and in situ silicate growth" approach under a relatively low hydrothermal temperature and alkali-free condition. The mesoporous manganese silicate shell provides a large specific surface area and abundant exposed Mn paramagnetic centers to water molecules, which endows the MMSSNs with extraordinarily high longitudinal relaxivity. Meanwhile, the MMSSNs presented an efficient pH/redox-responsive T1-MRI feature based on the significant enhancement of relaxation rate (r1) stimulated by mild acidic environment or reducing agent (GSH) both in vitro and in vivo. Furthermore, the mesoporous structure and negatively charged pore surface of the manganese silicate shell enable the MMSSNs to attain anti-cancer drug (DOX) storage and a pH-responsive release, which is suitable for on-demand drug release for the chemotherapy of tumors. Therefore, the mesoporous manganese silicate-based nanomaterial is a promising candidate as T1-MRI CAs and anticancer-drug delivery carriers for the theranostics of tumor in an intelligent and on-demand manner. MRI is one of the most frequently used imaging techniques in daily clinics for cancer diagnosis. Using contrast agents (CAs) in MRI can afford much clearer and enlarged images of detectable organs. Gadolinium (Gd(3+))-based T1-positive CAs are widely used but associated with the risk of nephrogenic systemic fibrosis. To achieve much safer CAs, various Mn(2+)-based T1-positive CAs have been reported, such as MnO or core-shell MnOx-based nanoparticles. However, the efficiency of these CAs is still lower. Herein, we report a novel kind of mesoporous manganese silicate coated silica nanoparticle as CA and anti-cancer drug carrier. Results obtained from this study, especially the p

  18. Novel ultrasound-responsive chitosan/perfluorohexane nanodroplets for image-guided smart delivery of an anticancer agent: Curcumin.

    PubMed

    Baghbani, Fatemeh; Chegeni, Mahdieh; Moztarzadeh, Fathollah; Hadian-Ghazvini, Samaneh; Raz, Majid

    2017-05-01

    Ultrasound-responsive nanodroplets are a class of new emerging smart drug delivery systems which provide image-guided nano-therapy of various diseases, especially cancers. Here, we developed multifunctional smart curcumin-loaded chitosan/perfluorohexane nanodroplets for contrast-ultrasound imaging and on-demand drug delivery. The nanodroplets were synthesized via nanoemulsion process. The optimal formulation with the size of 101.2nm and 77.8% curcumin entrapment was chosen for release study and cytotoxicity evaluation. Sonication at the frequency of 1MHz, 2W/cm(2) for 4min triggered the release of 63.5% of curcumin from optimal formulation (Cur-NDs-2). Ultrasound aided release study indicated that the concentration of perfluorohexane and the degree of acoustic droplet vaporization play important role in ultrasound-active drug release. B-mode ultrasound imaging confirmed strong ultrasound contrast of chitosan nanodroplets even at low concentrations via droplet to bubble transition. Finally, cytotoxicity of the ultrasound-responsive nanodroplets in the presence of ultrasound was evaluated in-vitro on 4T1 human breast cancer cells. Cell growth inhibitory effects of curcumin-loaded nanodroplets significantly increased by ultrasound exposure. According to the obtained results, these ultrasound responsive curcumin-loaded chitosan/perfluorohexane nanodroplets have a great potential for imaged-guided cancer therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

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

    PubMed

    Krautz-Peterson, Greice; Zhang, Yongrong; Chen, Kevin; Oyler, George A; Feng, Hanping; Shoemaker, Charles B

    2012-01-01

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

  20. Targeted delivery of cancer-specific multimodal contrast agents for intraoperative detection of tumor boundaries and therapeutic margins

    NASA Astrophysics Data System (ADS)

    Xu, Ronald X.; Xu, Jeff S.; Huang, Jiwei; Tweedle, Michael F.; Schmidt, Carl; Povoski, Stephen P.; Martin, Edward W.

    2010-02-01

    Background: Accurate assessment of tumor boundaries and intraoperative detection of therapeutic margins are important oncologic principles for minimal recurrence rates and improved long-term outcomes. However, many existing cancer imaging tools are based on preoperative image acquisition and do not provide real-time intraoperative information that supports critical decision-making in the operating room. Method: Poly lactic-co-glycolic acid (PLGA) microbubbles (MBs) and nanobubbles (NBs) were synthesized by a modified double emulsion method. The MB and NB surfaces were conjugated with CC49 antibody to target TAG-72 antigen, a human glycoprotein complex expressed in many epithelial-derived cancers. Multiple imaging agents were encapsulated in MBs and NBs for multimodal imaging. Both one-step and multi-step cancer targeting strategies were explored. Active MBs/NBs were also fabricated for therapeutic margin assessment in cancer ablation therapies. Results: The multimodal contrast agents and the cancer-targeting strategies were tested on tissue simulating phantoms, LS174 colon cancer cell cultures, and cancer xenograft nude mice. Concurrent multimodal imaging was demonstrated using fluorescence and ultrasound imaging modalities. Technical feasibility of using active MBs and portable imaging tools such as ultrasound for intraoperative therapeutic margin assessment was demonstrated in a biological tissue model. Conclusion: The cancer-specific multimodal contrast agents described in this paper have the potential for intraoperative detection of tumor boundaries and therapeutic margins.

  1. New approaches to antiretroviral drug delivery: challenges and opportunities associated with the use of long-acting injectable agents.

    PubMed

    Boffito, Marta; Jackson, Akil; Owen, Andrew; Becker, Stephen

    2014-01-01

    Research on improved treatment of HIV infection and pre-exposure prophylaxis continues. Poor adherence to treatment is the critical risk factor for virological failure and resistance development, and long-acting formulations of anti-HIV medications that need only infrequent dosing may facilitate long-term therapeutic responses. Importantly, long-acting formulations of therapeutic agents have been used to avoid missing doses or treatment fatigue to prescribed lifelong medications in a number of different medical fields, with demonstrable success. However, such formulations are associated with challenges, such as the prolongation of adverse events with the persistence of drug concentrations and concerns over the development of resistance as a result of selective pressure as drug concentrations decline. Furthermore, long-acting injectable formulations of antiretroviral (ARV) agents with infrequent dosing may be advantageous over daily oral drug intake to prevent transmission of HIV. However, the knowledge on protective drug concentrations and frequency of dosing is poor to date and implementation globally is challenging. Importantly, if nanoformulations of ARVs requiring lower drug doses become available globally, the potential for treatment cost reductions is high, as, especially in resource-limited settings, the active pharmaceutical ingredient accounts for the greater proportion of the total cost of the medicine. In conclusion, different long-acting ARVs are being studied in phase I/II for both the treatment and prevention of HIV infection, and research on administering these agents in combination has started.

  2. Novel Hydrogel Material as a Potential Embolic Agent in Embolization Treatments

    NASA Astrophysics Data System (ADS)

    Zhou, Feng; Chen, Liming; An, Qingzhu; Chen, Liang; Wen, Ying; Fang, Fang; Zhu, Wei; Yi, Tao

    2016-08-01

    We report a novel graphene-oxide (GO) enhanced polymer hydrogel (GPH) as a promising embolic agent capable of treating cerebrovascular diseases and malignant tumors, using the trans-catheter arterial embolization (TAE) technique. Simply composed of GO and generation five poly(amidoamine) dendrimers (PAMAM-5), our rheology experiments reveal that GPH exhibits satisfactory mechanical strength, which resist the high pressures of blood flow. Subcutaneous experiments on Sprague-Dawley (SD) rats demonstrate the qualified biocompatibility of GPH. Finally, our in vivo experiments on New Zealand rabbits, which mix GPH with the X-ray absorbing contrast agent, Iohexol, reveal complete embolization of the artery. We also note that GPH shortens embolization time and exhibits low toxicity in follow-up experiments. Altogether, our study demonstrates that GPH has many advantages over the currently used embolic agents and has potential applications in clinical practice.

  3. The poultry red mite (Dermanyssus gallinae): a potential vector of pathogenic agents.

    PubMed

    Valiente Moro, Claire; De Luna, Carlos J; Tod, Alexander; Guy, Jonathan H; Sparagano, Olivier A E; Zenner, Lionel

    2009-06-01

    The poultry red mite, D. gallinae has been involved in the transmission of many pathogenic agents, responsible for serious diseases both in animals and humans. Nowadays, few effective methods are available to control the ectoparasite in poultry farms. Consequently, this is an emerging problem which must be taken into account to maintain good health in commercial egg production. This paper addresses the vector capacity of the ectoparasite with special emphasis on salmonellae, pathogenic agents responsible for many of the most important outbreaks of food-borne diseases worlwide. It has been experimentally shown that D. gallinae could act as a biological vector of S. enteritidis and natural carriage of these bacteria by the mite on poultry premises has also been reported. It was also found that D. gallinae carried other pathogens such as E. coli, Shigella sp., and Staphylococcus, thus increasing the list of pathogenic agents potentially transmitted by the mite.

  4. Novel Hydrogel Material as a Potential Embolic Agent in Embolization Treatments

    PubMed Central

    Zhou, Feng; Chen, Liming; An, Qingzhu; Chen, Liang; Wen, Ying; Fang, Fang; Zhu, Wei; Yi, Tao

    2016-01-01

    We report a novel graphene-oxide (GO) enhanced polymer hydrogel (GPH) as a promising embolic agent capable of treating cerebrovascular diseases and malignant tumors, using the trans-catheter arterial embolization (TAE) technique. Simply composed of GO and generation five poly(amidoamine) dendrimers (PAMAM-5), our rheology experiments reveal that GPH exhibits satisfactory mechanical strength, which resist the high pressures of blood flow. Subcutaneous experiments on Sprague-Dawley (SD) rats demonstrate the qualified biocompatibility of GPH. Finally, our in vivo experiments on New Zealand rabbits, which mix GPH with the X-ray absorbing contrast agent, Iohexol, reveal complete embolization of the artery. We also note that GPH shortens embolization time and exhibits low toxicity in follow-up experiments. Altogether, our study demonstrates that GPH has many advantages over the currently used embolic agents and has potential applications in clinical practice. PMID:27561915

  5. Potential of Non-aqueous Microemulsions to Improve the Delivery of Lipophilic Drugs to the Skin.

    PubMed

    Carvalho, Vanessa F; de Lemos, Debora P; Vieira, Camila S; Migotto, Amanda; Lopes, Luciana B

    2017-07-01

    In this study, non-aqueous microemulsions were developed because of the challenges associated with finding pharmaceutically acceptable solvents for topical delivery of drugs sparingly soluble in water. The formulation irritation potential and ability to modulate the penetration of lipophilic compounds (progesterone, α-tocopherol, and lycopene) of interest for topical treatment/prevention of skin disorders were evaluated and compared to solutions and aqueous microemulsions of similar composition. The microemulsions (ME) were developed with BRIJ, vitamin E-TPGS, and ethanol as surfactant-co-surfactant blend and tributyrin, isopropyl myristate, and oleic acid as oil phase. As polar phase, propylene glycol (MEPG) or water (MEW) was used (26% w/w). The microemulsions were isotropic and based on viscosity and conductivity assessment, bicontinuous. Compared to drug solutions in lipophilic vehicles, MEPG improved drug delivery into viable skin layers by 2.5-38-fold; the magnitude of penetration enhancement mediated by MEPG into viable skin increased with drug lipophilicity, even though the absolute amount of drug delivered decreased. Delivery of progesterone and tocopherol, but not lycopene (the most lipophilic compound), increased up to 2.5-fold with MEW, and higher amounts of these two drugs were released from MEW (2-2.5-fold). Both microemulsions were considered safe for topical application, but MEPG-mediated decrease in the viability of reconstructed epidermis was more pronounced, suggesting its higher potential for irritation. We conclude that MEPG is a safe and suitable nanocarrier to deliver a variety of lipophilic drugs into viable skin layers, but the use of MEW might be more advantageous for drugs in the lower range of lipophilicity.

  6. Oxime ether lipids containing hydroxylated head groups are more superior siRNA delivery agents than their nonhydroxylated counterparts

    PubMed Central

    Gupta, Kshitij; Mattingly, Stephanie J; Knipp, Ralph J; Afonin, Kirill A; Viard, Mathias; Bergman, Joseph T; Stepler, Marissa; Nantz, Michael H; Puri, Anu; Shapiro, Bruce A

    2015-01-01

    Aim: To evaluate the structure–activity relationship of oxime ether lipids (OELs) containing modifications in the hydrophobic domains (chain length, degree of unsaturation) and hydrophilic head groups (polar domain hydroxyl groups) toward complex formation with siRNA molecules and siRNA delivery efficiency of resulting complexes to a human breast cancer cell line (MDA-MB-231). Materials & methods: Ability of lipoplex formation between oxime ether lipids with nucleic acids were examined using biophysical techniques. The potential of OELs to deliver nucleic acids and silence green fluorescent protein (GFP) gene was analyzed using MDA-MB-231 and MDA-MB-231/GFP cells, respectively. Results & conclusion: Introduction of hydroxyl groups to the polar domain of the OELs and unsaturation into the hydrophobic domain favor higher transfection and gene silencing in a cell culture system. PMID:26107486

  7. A double-targeted magnetic nanocarrier with potential application in hydrophobic drug delivery.

    PubMed

    Ding, Guobin; Guo, Yi; Lv, Yanyun; Liu, Xiaofeng; Xu, Li; Zhang, Xuezhong

    2012-03-01

    A double-targeted magnetic nanocarrier based with potential applications in the delivery of hydrophobic drugs has been developed. It consists of magnetite (Fe(3)O(4)) nanoparticles encapsulated in self-assembled micelles of the amphiphilic copolymer MPEG-PLGA [methoxy poly (ethylene glycol)-poly (d,l-lactide-co-glycolide)], and was fabricated using the solvent-evaporation technique. The magnetic nanocarrier has a very stable core-shell structure and is superparamagnetic. Its cytotoxicity was evaluated using the MTT assay with three cell lines-HeLa, MCF-7, and HT1080; it exhibited no cytotoxicity against any tested line at concentrations of up to 400 μg/mL after incubation for 24 h. Its cellular uptake was studied by Prussian blue staining and by fluorescence microscopy after encapsulating a fluorescent probe (hydrophobic quantum dots) into the nanocarrier. Finally, the magnetic targeting property of the magnetic nanocarrier was confirmed by an in vitro test. Overall, the results obtained demonstrate the potential of the double-targeted nanocarrier for the intracellular delivery of hydrophobic drugs.

  8. The potential of protein-nanomaterial interaction for advanced drug delivery.

    PubMed

    Peng, Qiang; Mu, Huiling

    2016-03-10

    Nanomaterials, like nanoparticles, micelles, nano-sheets, nanotubes and quantum dots, have great potentials in biomedical fields. However, their delivery is highly limited by the formation of protein corona upon interaction with endogenous proteins. This new identity, instead of nanomaterial itself, would be the real substance the organs and cells firstly encounter. Consequently, the behavior of nanomaterials in vivo is uncontrollable and some undesired effects may occur, like rapid clearance from blood stream; risk of capillary blockage; loss of targeting capacity; and potential toxicity. Therefore, protein-nanomaterial interaction is a great challenge for nanomaterial systems and should be inhibited. However, this interaction can also be used to functionalize nanomaterials by forming a selected protein corona. Unlike other decoration using exogenous molecules, nanomaterials functionalized by selected protein corona using endogenous proteins would have greater promise for clinical use. In this review, we aim to provide a comprehensive understanding of protein-nanomaterial interaction. Importantly, a discussion about how to use such interaction is launched and some possible applications of such interaction for advanced drug delivery are presented. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. The potential of adeno-associated viral vectors for gene delivery to muscle tissue

    PubMed Central

    Nahid, M Abu; Gao, Guangping

    2014-01-01

    Introduction Muscle-directed gene therapy is rapidly gaining attention primarily because muscle is an easily accessible target tissue and is also associated with various severe genetic disorders. Localized and systemic delivery of recombinant adeno-associated virus (rAAV) vectors of several serotypes results in very efficient transduction of skeletal and cardiac muscles, which has been achieved in both small and large animals, as well as in humans. Muscle is the target tissue in gene therapy for many muscular dystrophy diseases, and may also be exploited as a biofactory to produce secretory factors for systemic disorders. Current limitations of using rAAVs for muscle gene transfer include vector size restriction, potential safety concerns such as off-target toxicity and the immunological barrier composing of pre-existing neutralizing antibodies and CD8+ T-cell response against AAV capsid in humans. Areas covered In this article, we will discuss basic AAV vector biology and its application in muscle-directed gene delivery, as well as potential strategies to overcome the aforementioned limitations of rAAV for further clinical application. Expert opinion Delivering therapeutic genes to large muscle mass in humans is arguably the most urgent unmet demand in treating diseases affecting muscle tissues throughout the whole body. Muscle-directed, rAAV-mediated gene transfer for expressing antibodies is a promising strategy to combat deadly infectious diseases. Developing strategies to circumvent the immune response following rAAV administration in humans will facilitate clinical application. PMID:24386892

  10. The potential of adeno-associated viral vectors for gene delivery to muscle tissue.

    PubMed

    Wang, Dan; Zhong, Li; Nahid, M Abu; Gao, Guangping

    2014-03-01

    Muscle-directed gene therapy is rapidly gaining attention primarily because muscle is an easily accessible target tissue and is also associated with various severe genetic disorders. Localized and systemic delivery of recombinant adeno-associated virus (rAAV) vectors of several serotypes results in very efficient transduction of skeletal and cardiac muscles, which has been achieved in both small and large animals, as well as in humans. Muscle is the target tissue in gene therapy for many muscular dystrophy diseases, and may also be exploited as a biofactory to produce secretory factors for systemic disorders. Current limitations of using rAAVs for muscle gene transfer include vector size restriction, potential safety concerns such as off-target toxicity and the immunological barrier composing of pre-existing neutralizing antibodies and CD8(+) T-cell response against AAV capsid in humans. In this article, we will discuss basic AAV vector biology and its application in muscle-directed gene delivery, as well as potential strategies to overcome the aforementioned limitations of rAAV for further clinical application. Delivering therapeutic genes to large muscle mass in humans is arguably the most urgent unmet demand in treating diseases affecting muscle tissues throughout the whole body. Muscle-directed, rAAV-mediated gene transfer for expressing antibodies is a promising strategy to combat deadly infectious diseases. Developing strategies to circumvent the immune response following rAAV administration in humans will facilitate clinical application.

  11. Acceptability of Potential Rectal Microbicide Delivery Systems for HIV Prevention: A Randomized Crossover Trial

    PubMed Central

    Gorbach, Pamina M.; Weiss, Robert E.; Hess, Kristen; Murphy, Ryan; Saunders, Terry; Brown, Joelle; Anton, Peter A.; Cranston, Ross D.

    2012-01-01

    We assessed the acceptability of three of over-the-counter products representative of potential rectal microbicide (RM) delivery systems. From 2009 to 2010, 117 HIV-uninfected males (79 %) and females (21 %) who engage in receptive anal intercourse participated in a 6-week randomized crossover acceptability trial. Participants received each of three products (enema, lubricant-filled applicator, suppository) every 2 weeks in a randomized sequence. CASI and T-ACASI scales assessed product acceptability via Likert responses. Factor analysis was used to identify underlying factors measured by each scale. Random effects models were fit to examine age and gender effects on product acceptability. Three underlying factors were identified: Satisfaction with Product Use, Sexual Pleasure, and Ease of Product Use. For acceptability, the applicator ranked highest; however, differences between product acceptability scores were greatest among females and younger participants. These findings indicate that RM delivery systems impact their acceptability and should be considered early in RM development to enhance potential use. PMID:23114512

  12. Intracellular delivery of potential therapeutic genes: prospects in cancer gene therapy.

    PubMed

    Bakhtiar, Athirah; Sayyad, Mustak; Rosli, Rozita; Maruyama, Atsushi; Chowdhury, Ezharul H

    2014-01-01

    Conventional therapies for malignant cancer such as chemotherapy and radiotherapy are associated with poor survival rates owing to the development of cellular resistance to cancer drugs and the lack of targetability, resulting in unwanted adverse effects on healthy cells and necessitating the lowering of therapeutic dose with consequential lower efficacy of the treatment. Gene therapy employing different types of viral and non-viral carriers to transport gene(s) of interest and facilitating production of the desirable therapeutic protein(s) has tremendous prospects in cancer treatments due to the high-level of specificity in therapeutic action of the expressed protein(s) with diminished off-target effects, although cancer cell-specific delivery of transgene(s) still poses some challenges to be addressed. Depending on the potential therapeutic target genes, cancer gene therapy could be categorized into tumor suppressor gene replacement therapy, immune gene therapy and enzyme- or prodrug-based therapy. This review would shed light on the current progress of delivery of potentially therapeutic genes into various cancer cells in vitro and animal models utilizing a variety of viral and non-viral vectors.

  13. Potentials of Chitosan-Based Delivery Systems in Wound Therapy: Bioadhesion Study

    PubMed Central

    Hurler, Julia; Škalko-Basnet, Nataša

    2012-01-01

    Chitosan is currently proposed to be one of the most promising polymers in wound dressing development. Our research focuses on its potential as a vehicle for nano-delivery systems destined for burn therapy. One of the most important features of wound dressing is its bioadhesion to the wounded site. We compared the bioadhesive properties of chitosan with those of Carbopol, a synthetic origin polymer. Chitosan-based hydrogels of different molecular weights were first analyzed by texture analysis for gel cohesiveness, adhesiveness and hardness. In vitro release studies showed no difference in release of model antimicrobial drug from the different hydrogel formulations. Bioadhesion tests were performed on pig ear skin and the detachment force, necessary to remove the die from the skin, and the amount of remaining formulation on the skin were determined. Although no significant difference regarding detachment force could be seen between Carbopol-based and chitosan-based formulations, almost double the amount of chitosan formulation remained on the skin as compared to Carbopol formulations. The findings confirmed the great potential of chitosan-based delivery systems in advanced wound therapy. Moreover, results suggest that formulation retention on the ex vivo skin samples could provide deeper insight on formulation bioadhesiveness than the determination of detachment force. PMID:24956514

  14. Poly methacrylic acid modified CDHA nanocomposites as potential pH responsive drug delivery vehicles.

    PubMed

    Victor, Sunita Prem; Sharma, Chandra P

    2013-08-01

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

  15. A potential carrier based on liquid crystal nanoparticles for ophthalmic delivery of pilocarpine nitrate.

    PubMed

    Li, Jing; Wu, Lin; Wu, Weijun; Wang, Baoyan; Wang, Zhongyuan; Xin, Hongliang; Xu, Qunwei

    2013-10-15

    Poor corneal penetration and short preocular retention of a clinical hydrophilic drug, pilocarpine nitrate (PN), for the treatment of open-angle glaucoma and acute angle-closure glaucoma, limit its ocular application. The purpose of this study was to investigate the potential of liquid crystal nanoparticles (LCNPs) for ocular delivery of PN. LCNPs were developed by a top-down method using glyceryl monoolein (GMO) and water in the presence of stabilizer Poloxamer 407. They were characterized by transmission electron microscopy (TEM) and small angle X-ray diffraction (SAXS). The size of LCNP is 202.28±19.32 nm and the encapsulation efficiency reached 61.03%. The in vitro release profiles indicated that PN could keep sustained release from PN-loaded LCNPs for 8h. An ex vivo corneal permeation study revealed that the apparent permeability coefficient of PN-loaded LCNPs was 2.05-fold higher than that of commercial eye drops. In addition, the topical administration test showed that PN-loaded LCNPs had a prolonged effect on decreasing intraocular pressure (IOP) of rabbits compared with commercial drug and physiological saline. In conclusion, LCNPs had been demonstrated to be potential for controlled-release ocular drug delivery. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. Polyethylenimine functionalized magnetic nanoparticles as a potential non-viral vector for gene delivery.

    PubMed

    Zhou, Yangbo; Tang, Zhaomin; Shi, Chunli; Shi, Shuai; Qian, Zhiyong; Zhou, Shaobing

    2012-11-01

    Polyethylenimine (PEI) functionalized magnetic nanoparticles were synthesized as a potential non-viral vector for gene delivery. The nanoparticles could provide the magnetic-targeting, and the cationic polymer PEI could condense DNA and avoid in vitro barriers. The magnetic nanoparticles were characterized by Fourier transform infrared spectroscopy, X-ray powder diffraction, dynamic light scattering measurements, transmission electron microscopy, vibrating sample magnetometer and atomic force microscopy. Agarose gel electrophoresis was used to asses DNA binding and perform a DNase I protection assay. The Alamar blue assay was used to evaluate negative effects on the metabolic activity of cells incubated with PEI modified magnetic nanoparticles and their complexes with DNA both in the presence or absence of an external magnetic field. Flow cytometry and fluorescent microscopy were also performed to investigate the transfection efficiency of the DNA-loaded magnetic nanoparticles in A549 and B16-F10 tumor cells with (+M) or without (-M) the magnetic field. The in vitro transfection efficiency of magnetic nanoparticles was improved obviously in a permanent magnetic field. Therefore, the magnetic nanoparticles show considerable potential as nanocarriers for gene delivery.

  17. pH Effect on the binding of chlorin derivatives with Cremophor EL, a potential drug delivery vehicle

    NASA Astrophysics Data System (ADS)

    Patel, Sunita; Datta, Anindya

    2005-09-01

    The binding of chlorin p6 with Cremophor EL (CrEL) at pH 5 and pH 7 has been monitored by fluorescence techniques. Upon binding with the drug delivery agent, the fluorescent species are found to be one and the same at both pH values. This is explained by a hindrance to protonation of chlorin p6 trianions by Cremophor EL. Surprisingly, it is the more hydrophilic species between the two possible chlorin p6 ions that is found to get bound preferentially with the hydrophobic delivery medium.

  18. Polymersomes conjugated with des-octanoyl ghrelin for the delivery of therapeutic and imaging agents into brain tissues.

    PubMed

    Chen, Yung-Chu; Chiang, Chi-Feng; Chen, Li-Fang; Liao, Shu-Chuan; Hsieh, Wen-Yuan; Lin, Win-Li

    2014-02-01

    The effective protection of the blood-brain barrier (BBB) from tight junctions and efflux transport systems ultimately results in the limited entry of 95% of drug/gene candidates, which are potentially beneficial for central nervous system (CNS) diseases. In order to enhance the brain-specific delivery, in this study we developed a targeting carrier system, which consists of poly(carboxyl ethylene glycol-g-glutamate)-co-poly(distearin-g-glutamate) (CPEGGM-PDSGM) polymersomes with the conjugation of des-octanoyl ghrelin. Des-octanoyl ghrelin across the BBB was reported to be unidirectional (blood-to-brain direction). However, there is no report about the conjugation of des-octanoyl ghrelin to a drug carrier system to confer the BBB targeting property through des-octanoyl ghrelin binding sites mediated endocytosis. To qualitatively and quantitatively investigate this carrier's properties, coumarin 6, Cy5.5 and met-enkephalin were individually encapsulated in these polymersomes. The experimental results showed that the cellular uptake was significantly higher for des-octanoyl ghrelin-conjugated polymersomes (GPs) than unconjugated polymersomes when co-incubated with the BBB cells. In addition, an enhanced accumulation in brain together with a reduced accumulation in liver and spleen was observed in animal study, indicating better brain selectivity for the GPs. In a hot-plate test, a significant inhibition of nociceptive response could be achieved for an intravenous injection of GPs encapsulated with met-enkephalin. The overall results demonstrated that GPs own a great potential for targeting delivery of drug across the BBB to treat CNS diseases. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Opportunities for Web-based Drug Repositioning: Searching for Potential Antihypertensive Agents with Hypotension Adverse Events.

    PubMed

    Wang, Kejian; Wan, Mei; Wang, Rui-Sheng; Weng, Zuquan

    2016-04-01

    Drug repositioning refers to the process of developing new indications for existing drugs. As a phenotypic indicator of drug response in humans, clinical side effects may provide straightforward signals and unique opportunities for drug repositioning. We aimed to identify drugs frequently associated with hypotension adverse reactions (ie, the opposite condition of hypertension), which could be potential candidates as antihypertensive agents. We systematically searched the electronic records of the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) through the openFDA platform to assess the association between hypotension incidence and antihypertensive therapeutic effect regarding a list of 683 drugs. Statistical analysis of FAERS data demonstrated that those drugs frequently co-occurring with hypotension events were more likely to have antihypertensive activity. Ranked by the statistical significance of frequent hypotension reporting, the well-known antihypertensive drugs were effectively distinguished from others (with an area under the receiver operating characteristic curve > 0.80 and a normalized discounted cumulative gain of 0.77). In addition, we found a series of antihypertensive agents (particularly drugs originally developed for treating nervous system diseases) among the drugs with top significant reporting, suggesting the good potential of Web-based and data-driven drug repositioning. We found several candidate agents among the hypotension-related drugs on our list that may be redirected for lowering blood pressure. More important, we showed that a pharmacovigilance system could alternatively be used to identify antihypertensive agents and sustainably create opportunities for drug repositioning.

  20. Hypertension and vascular dementia in the elderly: the potential role of anti-hypertensive agents.

    PubMed

    Coca, Antonio

    2013-09-01

    Vascular dementia (VaD) - a severe form of vascular cognitive impairment - and cognitive decline are associated with hypertension and therefore it seems logical to consider that reducing BP with anti-hypertensive therapy may protect against the development/onset of cognitive function impairment or dementia. This narrative, non-systematic review discusses the available evidence on the potential correlation between the use of anti-hypertensive agents and the risk of VaD and cognitive decline. MEDLINE was searched for inclusion of relevant studies. No limitations in time were considered. A consensus on the potential effects of anti-hypertensive treatment in the reduction of VaD and associated cognitive decline has not been reached. A protective effect of anti-hypertensive agents has been observed in a number of studies although it is still unclear whether different classes of anti-hypertensive agents have a different effect on the development of VaD. The protective effect of anti-hypertensive agents appears to depend on the specific drug used - positive effects have been observed with calcium channel blockers (CCBs), such as lercanidipine and nitrendipine, the combination perindopril-indapamide and telmisartan.

  1. The potential role of natural agents in treatment of airway inflammation.

    PubMed

    Sharafkhaneh, Amir; Velamuri, Suryakanta; Badmaev, Vladimir; Lan, Charlie; Hanania, Nicola

    2007-12-01

    Obstructive airway diseases including asthma, chronic obstructive pulmonary disease and cystic fibrosis present with dyspnea and variety of other symptoms. Physiologically, they are characterized by maximal expiratory flow limitation and pathologically, by inflammation of the airways and the lung parenchyma. Inflammation plays a major role in the gradual worsening of the lung function resulting in worsening symptoms. For many years, scientists focused their efforts in identifying various pathways involved in the chronic inflammation present in these diseases. Further, studies are underway to identify various molecular targets in these pathways for the purpose of developing novel therapeutic agents. Natural agents have been used for thousands of years in various cultures for the treatment of several medical conditions and have mostly proven to be safe. Recent in vivo and in vitro studies show potential anti-inflammatory role for some of the existing natural agents. This review provides an overview of the literature related to the anti-inflammatory effects of some of the natural agents which have potential value in the treatment of inflammatory lung diseases.

  2. Surface Modifications of Titanium Implants by Multilayer Bioactive Coatings with Drug Delivery Potential: Antimicrobial, Biological, and Drug Release Studies

    NASA Astrophysics Data System (ADS)

    Ordikhani, Farideh; Zustiak, Silviya Petrova; Simchi, Abdolreza

    2016-04-01

    Recent strategies to locally deliver antimicrobial agents to combat implant-associated infections—one of the most common complications in orthopedic surgery—are gaining interest. However, achieving a controlled release profile over a desired time frame remains a challenge. In this study, we present an innovative multifactorial approach to combat infections which comprises a multilayer chitosan/bioactive glass/vancomycin nanocomposite coating with an osteoblastic potential and a drug delivery capacity. The bioactive drug-eluting coating was prepared on the surface of titanium foils by a multistep electrophoretic deposition technique. The adopted deposition strategy allowed for a high antibiotic loading of 1038.4 ± 40.2 µg/cm2. The nanocomposite coating exhibited a suppressed burst release with a prolonged sustained vancomycin release for up to 6 weeks. Importantly, the drug release profile was linear with respect to time, indicating a zero-order release kinetics. An in vitro bactericidal assay against Staphylococcus aureus confirmed that releasing the drug reduced the risk of bacterial infection. Excellent biocompatibility of the developed coating was also demonstrated by in vitro cell studies with a model MG-63 osteoblast cell line.

  3. Focused ultrasound delivery of Raman nanoparticles across the blood-brain barrier: Potential for targeting experimental brain tumors

    PubMed Central

    Diaz, Roberto Jose; McVeigh, Patrick Z.; O’Reilly, Meaghan A.; Burrell, Kelly; Bebenek, Matthew; Smith, Christian; Etame, Arnold; Zadeh, Gelareh; Hynynen, Kullervo; Wilson, Brian C.; Rutka, James T.

    2014-01-01

    Spectral mapping of nanoparticles with surface enhanced Raman scattering (SERS) capability in the near-infrared range is an emerging molecular imaging technique. We used magnetic resonance image-guided transcranial focused ultrasound (TcMRgFUS) to reversibly disrupt the blood-brain barrier (BBB) adjacent to brain tumor margins in rats. Glioma cells were found to internalize SERS capable nanoparticles of 50 nm or 120 nm physical diameter. Surface coating with anti-epidermal growth factor receptor antibody or non-specific human immunoglobulin G, resulted in enhanced cell uptake of nanoparticles in-vitro compared to nanoparticles with methyl terminated 12-unit polyethylene glycol surface. BBB disruption permitted the delivery of SERS capable spherical 50 or 120 nm gold nanoparticles to the tumor margins. Thus, nanoparticles with SERS imaging capability can be delivered across the BBB non-invasively using TcMRgFUS and have the potential to be used as optical tracking agents at the invasive front of malignant brain tumors. PMID:24374363

  4. Targeted pulmonary delivery of inducers of host macrophage autophagy as a potential host-directed chemotherapy of tuberculosis☆

    PubMed Central

    Gupta, Anuradha; Misra, Amit; Deretic, Vojo

    2017-01-01

    One of the promising host-directed chemotherapeutic interventions in tuberculosis (TB) is based on inducing autophagy as an immune effector. Here we consider the strengths and weaknesses of potential autophagy-based pharmacological intervention. Using the existing drugs that induce autophagy is an option, but it has limitations given the broad role of autophagy in most cells, tissues, and organs. Thus, it may be desirable that the agent being used to modulate autophagy is applied in a targeted manner, e.g. delivered to affected tissues, with infected macrophages being an obvious choice. This review addresses the advantages and disadvantages of delivering drugs to induce autophagy in M. tuberculosis-infected macrophages. One option, already being tested in models, is to design particles for inhalation delivery to lung macrophages. The choice of drugs, drug release kinetics and intracellular residence times, non-target cell exposure and feasibility of use by patients is discussed. We term here this (still experimental) approach, of compartment-targeting, autophagy-based, host-directed therapy as “Track-II antituberculosis chemotherapy.” PMID:26829287

  5. Potential Renoprotective Agents through Inhibiting CTGF/CCN2 in Diabetic Nephropathy

    PubMed Central

    Wang, Songyan; Li, Bing; Li, Chunguang; Cui, Wenpeng; Miao, Lining

    2015-01-01

    Diabetic nephropathy (DN) is the leading cause of end-stage renal disease (ESRD). The development and progression of DN might involve multiple factors. Connective tissue growth factor (CCN2, originally known as CTGF) is the one which plays a pivotal role. Therefore, increasing attention is being paid to CCN2 as a potential therapeutic target for DN. Up to date, there are also many drugs or agents which have been shown for their protective effects against DN via different mechanisms. In this review, we only focus on the potential renoprotective therapeutic agents which can specifically abolish CCN2 expression or nonspecifically inhibit CCN2 expression for retarding the development and progression of DN. PMID:26421309

  6. The stimulation of bioluminescence in Photobacterium leiognathi as a potential prescreen for antitumor agents.

    PubMed

    Steinberg, D A; Peterson, G A; White, R J; Maiese, W M

    1985-10-01

    The stimulation of bioluminescence in Photobacterium leiognathi has previously been described as a test for genotoxic compounds. An adaptation of this procedure has been developed which uses a dim variant of P. leiognathi and permits the prescreening of microbial fermentation broths for potential antitumor agents. Bioluminescence in this organism was stimulated by compounds which bind to DNA or affect DNA synthesis. Antibiotics with target sites such as protein, cell wall or RNA synthesis, did not alter bioluminescence. Fermentation broths from over 5,000 soil isolates were prescreened in this assay and 95 (1.6%) were defined as active. Further analysis of selected cultures suggested that about half produced compound(s) with DNA-binding activity. These results suggest that the photobacterium induction assay (PIA) may be useful as a prescreen for potential antitumor agents. The assay is rapid, simple and requires only microgram quantities of material for testing.

  7. Potentiation of the depression by adenosine of rat cerebral cortical neurones by progestational agents.

    PubMed Central

    Phillis, J. W.

    1986-01-01

    The effects of four progestational agents pregnenolone sulphate, cyproterone acetate, norethindrone acetate and progesterone, on adenosine-evoked depression of the firing of rat cerebral cortical neurones have been studied. When applied iontophoretically, pregnenolone sulphate, cyproterone, and norethindrone enhanced the actions of iontophoretically applied adenosine and failed to potentiate the depressant effects of adenosine 5'-N-ethylcarboxamide and gamma-aminobutyric acid. Cyproterone acetate (50 micrograms kg-1) and progesterone (200 micrograms kg-1) administered intravenously enhanced the depressant actions of iontophoretically applied adenosine. When applied by large currents, cyproterone, and less frequently norethindrone, depressed the firing of cerebral cortical neurones. The depressant effects of cyproterone were antagonized by caffeine. Pregnenolone sulphate tended to excite cortical neurones but neither this action, nor its potentiation of adenosine were reproduced by application of sulphate ions. It is hypothesized that some of the psychotropic actions of progestational agents may involve an enhancement of 'purinergic' tone in the central nervous system. PMID:3814905

  8. Polysaccharides as Bacterial Antiadhesive Agents and "Smart" Constituents for Improved Drug Delivery Systems Against Helicobacter pylori Infection.

    PubMed

    Menchicchi, Bianca; Hensel, Andreas; Goycoolea, Francisco M

    2015-01-01

    The standard eradication treatment of the hostile Helicobacter pylori (H. pylori) stomach infection is facing increasing alarming antibiotic resistance worldwide and calls for alternative strategies to the use of antibiotics. One new perspective in this direction is cytoprotective compounds for targeted prevention of the adhesion of the bacteria to the stomach host cell and to inhibit the bacterial cell-cell communication via quorum sensing by specific inhibitors. Bacterial adhesion of H. pylori to the host cells is mainly mediated by carbohydrate-protein interactions. Therefore, the use of polyvalent carbohydrates, (e.g. plant-derived polysaccharides), as potential antiadhesive compounds, seems to be a promising tool to prevent the initial docking of the bacterium to the stomach cells. Polysaccharides are common constituents of daily food, either as starch or as dietary fiber and often also function as excipients for galenic drug-delivery formulations. In addition, polysaccharides with defined pharmacodynamics action against bacterial outer membrane proteins can have potential as therapeutic tools in the treatment of bacterial infections. Some polysaccharides are known to possess antibacterial properties against gram-positive bacteria, others to inhibit bacterial colonization by blocking specific carbohydrate receptors involved in host-bacteria interaction. This mode of action is advocated as alternative antiadhesion therapy. Ongoing research is also seeking for polysaccharide-based nanoformulations with potential for local drug delivery at the stomach as novel H. pylori therapies. These approaches pose challenges concerned with the stability of the nanomaterials in the harsh conditions of the gastric environment and their capacity to adhere to the stomach mucosa. In a global scenario, geographical diversity and social habits, namely lifestyle and dietary factors, influence the prevalence of the H. pylori-associated diseases and their severity. In this context

  9. Potential for Terahertz/Optical, Two Color Non-linear Sensing of Liquid Biochemical Agents

    DTIC Science & Technology

    2011-05-18

    solutions1,2 in the infrared frequency band. To explore the lowest frequency macromo- lecular modes of biomolecules, which occur at terahertz fre- quencies, in...resonant with elec- tronic excitations and macromolecular vibrations . A configuration that optimizes SDFG in the face of strong terahertz absorption by...REPORT Potential for terahertz /optical, two color non-linear sensing of liquid biochemical agents 14. ABSTRACT 16. SECURITY CLASSIFICATION OF: A high

  10. Synthesis, antifungal activities and qualitative structure activity relationship of carabrone hydrazone derivatives as potential antifungal agents.

    PubMed

    Wang, Hao; Ren, Shuang-Xi; He, Ze-Yu; Wang, De-Long; Yan, Xiao-Nan; Feng, Jun-Tao; Zhang, Xing

    2014-03-11

    Aimed at developing novel fungicides for relieving the ever-increasing pressure of agricultural production caused by phytopathogenic fungi, 28 new hydrazone derivatives of carabrone, a natural bioactive sesquisterpene, in three types were designed, synthesized and their antifungal activities against Botrytis cinerea and Colletotrichum lagenarium were evaluated. The result revealed that all the derivatives synthesized exhibited considerable antifungal activities in vitro and in vivo, which led to the improved activities for carabrone and its analogues and further confirmed their potential as antifungal agents.

  11. MRI in ocular drug delivery.

    PubMed

    Li, S Kevin; Lizak, Martin J; Jeong, Eun-Kee

    2008-11-01

    Conventional pharmacokinetic methods for studying ocular drug delivery are invasive and cannot be conveniently applied to humans. The advancement of MRI technology has provided new opportunities in ocular drug-delivery research. MRI provides a means to non-invasively and continuously monitor ocular drug-delivery systems with a contrast agent or compound labeled with a contrast agent. It is a useful technique in pharmacokinetic studies, evaluation of drug-delivery methods, and drug-delivery device testing. Although the current status of the technology presents some major challenges to pharmaceutical research using MRI, it has a lot of potential. In the past decade, MRI has been used to examine ocular drug delivery via the subconjunctival route, intravitreal injection, intrascleral injection to the suprachoroidal space, episcleral and intravitreal implants, periocular injections, and ocular iontophoresis. In this review, the advantages and limitations of MRI in the study of ocular drug delivery are discussed. Different MR contrast agents and MRI techniques for ocular drug-delivery research are compared. Ocular drug-delivery studies using MRI are reviewed.

  12. MRI in ocular drug delivery

    PubMed Central

    Li, S. Kevin; Lizak, Martin J.; Jeong, Eun-Kee

    2008-01-01

    Conventional pharmacokinetic methods for studying ocular drug delivery are invasive and cannot be conveniently applied to humans. The advancement of MRI technology has provided new opportunities in ocular drug-delivery research. MRI provides a means to non-invasively and continuously monitor ocular drug-delivery systems with a contrast agent or compound labeled with a contrast agent. It is a useful technique in pharmacokinetic studies, evaluation of drug-delivery methods, and drug-delivery device testing. Although the current status of the technology presents some major challenges to pharmaceutical research using MRI, it has a lot of potential. In the past decade, MRI has been used to examine ocular drug delivery via the subconjunctival route, intravitreal injection, intrascleral injection to the suprachoroidal space, episcleral and intravitreal implants, periocular injections, and ocular iontophoresis. In this review, the advantages and limitations of MRI in the study of ocular drug delivery are discussed. Different MR contrast agents and MRI techniques for ocular drug-delivery research are compared. Ocular drug-delivery studies using MRI are reviewed. PMID:18186077

  13. Development of an intrabiliary MR imaging-monitored local agent delivery technique: a feasibility study in pigs.

    PubMed

    Zhang, Feng; Li, Jiakai; Meng, Yanfeng; Sun, Jihong; Soriano, Stephanie S; Willis, Patrick; Gu, Huidong; Glickerman, David; Yang, Xiaoming

    2012-03-01

    To investigate the feasibility of using magnetic resonance (MR) imaging to monitor intrabiliary delivery of motexafin gadolinium (MGd) into pig common bile duct (CBD) walls. Animal studies were approved by the Institutional Animal Care and Use Committee. Initially, human cholangiocarcinoma cells were treated with various concentrations of MGd, a compound serving as a T1-weighted MR imaging contrast agent, chemotherapy drug, and cell marker. These cells were then examined by means of confocal microscopy to confirm the intracellular uptake of MGd. In addition, an MGd/trypan blue mixture was locally infused into CBD walls of six cadaveric pigs using a microporous balloon catheter. CBDs of six pigs were infused with saline to serve as controls. Ex vivo T1-weighted MR imaging of these CBDs was performed. For in vivo technical validation, the microporous balloon catheter was placed in the CBD by means of a transcholecytic access to deliver MGd/trypan blue into CBD walls of six living pigs. T1-weighted images were obtained with both a surface coil and an intrabiliary MR imaging guidewire, and contrast-to-noise ratios of CBD walls before and after MGd/trypan blue infusions were compared in the two groups by means of paired t test, with subsequent histologic analysis to confirm the penetration and distribution of the MGd/trypan blue agent into CBD walls. In vitro experiments confirmed uptake of MGd by human cholangiocarcinoma cells. The ex vivo experiments demonstrated the penetration of MGd/trypan blue into the CBD walls. The in vivo experiment confirmed the uptake of MGd/trypan blue, showing an increased contrast-to-noise ratio for the CBD after administration of the mixture, compared with images obtained prior to MGd/trypan blue administration (11.6 ± 4.2 [standard deviation] vs 5.7 ± 2.8; P = .04). Histologic results depicted the blue dye stains and red fluorescence of MGd in CBD walls, confirming the imaging findings. It is feasible to use MR imaging to monitor the

  14. Development of an Intrabiliary MR Imaging-monitored Local Agent Delivery Technique: A Feasibility Study in Pigs

    PubMed Central

    Zhang, Feng; Li, Jiakai; Meng, Yanfeng; Sun, Jihong; Soriano, Stephanie S.; Willis, Patrick; Gu, Huidong; Glickerman, David

    2012-01-01

    Purpose: To investigate the feasibility of using magnetic resonance (MR) imaging to monitor intrabiliary delivery of motexafin gadolinium (MGd) into pig common bile duct (CBD) walls. Materials and Methods: Animal studies were approved by the Institutional Animal Care and Use Committee. Initially, human cholangiocarcinoma cells were treated with various concentrations of MGd, a compound serving as a T1-weighted MR imaging contrast agent, chemotherapy drug, and cell marker. These cells were then examined by means of confocal microscopy to confirm the intracellular uptake of MGd. In addition, an MGd/trypan blue mixture was locally infused into CBD walls of six cadaveric pigs using a microporous balloon catheter. CBDs of six pigs were infused with saline to serve as controls. Ex vivo T1-weighted MR imaging of these CBDs was performed. For in vivo technical validation, the microporous balloon catheter was placed in the CBD by means of a transcholecytic access to deliver MGd/trypan blue into CBD walls of six living pigs. T1-weighted images were obtained with both a surface coil and an intrabiliary MR imaging guidewire, and contrast-to-noise ratios of CBD walls before and after MGd/trypan blue infusions were compared in the two groups by means of paired t test, with subsequent histologic analysis to confirm the penetration and distribution of the MGd/trypan blue agent into CBD walls. Results: In vitro experiments confirmed uptake of MGd by human cholangiocarcinoma cells. The ex vivo experiments demonstrated the penetration of MGd/trypan blue into the CBD walls. The in vivo experiment confirmed the uptake of MGd/trypan blue, showing an increased contrast-to-noise ratio for the CBD after administration of the mixture, compared with images obtained prior to MGd/trypan blue administration (11.6 ± 4.2 [standard deviation] vs 5.7 ± 2.8; P = .04). Histologic results depicted the blue dye stains and red fluorescence of MGd in CBD walls, confirming the imaging findings

  15. Effects of pore forming agents on chitosan-graft-poly(N-vinylpyrrolidone) hydrogel properties for use as a matrix for floating drug delivery

    NASA Astrophysics Data System (ADS)

    Budianto, E.; Al-Shidqi, M. F.; Cahyana, A. H.

    2017-07-01

    Eradicating H. pylori-based infection by using conventional oral dosage form of amoxicillin trihydrate finds difficulties to overcome rapid gastric retention time. Encapsulating amoxicillin trihydrate in floating drug delivery system may solve the problem. In this research, the floating drug delivery system of amoxicillin trihydrate encapsulated in floating chitosan-graft-poly(N-vinyl pyrrolidone) hydrogels containing CaCO3 and NaHCO3 as pore forming agents has been successfully prepared. Pore forming agents used was varied with the ratio of 10 to 25% pore forming agents to total mass of the used materials. The hydrogel were characterizedusing FTIR spectrophotometer and stereo microscope. As pore forming agents compositions increased, the porosity (%) and floating properties increased but followed by decrease in drug entrapment efficiency. Most of the floating hydrogels possessed floating ability longer than 180 min and the highest porosity was found in hydrogel containing 25% NaHCO3. Hydrogel containing CaCO3 showed sustained drug release profile than hydrogel containing NaHCO3. However, the optimum formulation was achieved at composition of 10% NaHCO3 with 57% of drug entrapped within the hydrogel and 43% drug released. The results of these studies show that NaHCO3 is an effective pore forming agents for chitosan-graft-poly(N-vinyl pyrrolidone) hydrogel preparation as compare to CaCO3.

  16. Delivery of optical contrast agents using Triton-X100, part 2: enhanced mucosal permeation for the detection of cancer biomarkers

    NASA Astrophysics Data System (ADS)

    van de Ven, Anne L.; Adler-Storthz, Karen; Richards-Kortum, Rebecca

    2009-03-01

    Uniform delivery of optical contrast agents through mucosal tissue has proven a significant challenge. Topical permeation enhancers that have proven useful for skin demonstrate limited success in mucosal tissue. We sought to develop a topical permeation strategy capable of delivering tissue-impermeant molecular-specific contrast agents through mucosal epithelium in a uniform, controlled manner. We demonstrate that Triton-X100 can be utilized to deliver targeted and untargeted optical contrast agents through freshly excised normal mucosal epithelium and epithelial cancer. Macromolecules up to 150 kDa in size were successfully delivered via transcellular and paracellular routes. The depth of Triton-mediated permeation was modulated by varying the treatment time and concentration. Uniform epithelial penetration to a depth of 500 μm was achieved in ~1.5 h for molecules of 40 kDa or less. Larger optical probes required longer treatment times. Coadministration of molecular-specific contrast agents with Triton-X100 treatment facilitated simultaneous labeling of biomarkers on the cell membrane, in the cytoplasm, and in the nucleus with high specificity. Together, these data suggest that Triton-X100 is a promising topical permeation enhancer for mucosal delivery of tissue-impermeant molecular-specific optical contrast agents.

  17. Natural product modulators of transient receptor potential (TRP) channels as potential anti-cancer agents.

    PubMed

    Rodrigues, Tiago; Sieglitz, Florian; Bernardes, Gonçalo J L

    2016-11-07

    Treatment of cancer is a significant challenge in clinical medicine, and its research is a top priority in chemical biology and drug discovery. Consequently, there is an urgent need for identifying innovative chemotypes capable of modulating unexploited drug targets. The transient receptor potential (TRPs) channels persist scarcely explored as targets, despite intervening in a plethora of pathophysiological events in numerous diseases, including cancer. Both agonists and antagonists have proven capable of evoking phenotype changes leading to either cell death or reduced cell migration. Among these, natural products entail biologically pre-validated and privileged architectures for TRP recognition. Furthermore, several natural products have significantly contributed to our current knowledge on TRP biology. In this Tutorial Review we focus on selected natural products, e.g. capsaicinoids, cannabinoids and terpenes, by highlighting challenges and opportunities in their use as starting points for designing natural product-inspired TRP channel modulators. Importantly, the de-orphanization of natural products as TRP channel ligands may leverage their exploration as viable strategy for developing anticancer therapies. Finally, we foresee that TRP channels may be explored for the selective pharmacodelivery of cytotoxic payloads to diseased tissues, providing an innovative platform in chemical biology and molecular medicine.

  18. Using serum CA125 to assess the activity of potential cytostatic agents in ovarian cancer.

    PubMed

    Hall, Marcia R; Petruckevitch, Ann; Pascoe, Joanna; Persic, Mojca; Tahir, Saad; Morgan, Jamie S; Gourley, Charlie; Stuart, Nick; Crawford, S Michael; Kornbrot, Diana E; Qian, Wendi; Rustin, Gordon J

    2014-05-01

    New strategies are required to rapidly identify novel cytostatic agents before embarking on large randomized trials. This study investigates whether a change in rate of rise (slope) of serum CA125 from before to after starting a novel agent could be used to identify cytostatic agents. Tamoxifen was used to validate this hypothesis. Asymptomatic patients with relapsed ovarian cancer who had responded to chemotherapy were enrolled and had CA125 measurements taken every 4 weeks, then more frequently when rising. Once levels reached 4 times the upper limit of normal or nadir, they started continuous tamoxifen 20 mg daily, as well as fortnightly CA125 measurements until symptomatic progression. Because of the potentially nonlinear relationship of CA125 over time, it was felt that to enable normal approximations to be utilized a natural logarithmic standard transformation [ln(CA125)] was the most suitable to improve linearity above the common logarithmic transformation to base 10. From 235 recruited patients, 81 started tamoxifen and had at least 4 CA125 measurements taken before and 4 CA125 measurements taken after starting tamoxifen, respectively. The mean regression slopes from using at least 4 1n(CA125) measurements immediately before and after starting tamoxifen were 0·0149 and 0·0093 [ln(CA125)/d], respectively. This difference is statistically significant, P = 0·001. Therefore, in a future trial with a novel agent, at least as effective as tamoxifen, using this effect size, the number of evaluable patients needed, at significance level of 5% and power of 80%, is 56. Further validation of this methodology is required, but there is potential to use comparison of mean regression slopes of ln(CA125) as an interim analysis measure of efficacy for novel cytostatic agents in relapsed ovarian cancer.

  19. Histological evaluation of follicular delivery of arginine via nanostructured lipid carriers: a novel potential approach for the treatment of alopecia.

    PubMed

    Yazdani-Arazi, Seyedeh Narjes; Ghanbarzadeh, Saeed; Adibkia, Khosro; Kouhsoltani, Maryam; Hamishehkar, Hamed

    2016-10-31

    The use of lipidic nanoparticles can overcome the limitations of skin penetration of hydrophilic charged materials. Oleic acid as an ion pairing agent was used to enhance the encapsulation of positively charged arginine into lipophilic nanostructured lipid carrier (NLC). Histological study on the male hamsters was performed to assess the efficiency of drug delivery on hair growth. The accumulation of NLCs in the hair follicles was verified and in vivo studies showed more new hair follicle growth by utilizing arginine-loaded NLCs than arginine aqueous solution. It was concluded that employing ion pairing agent could enhance drug encapsulation into NLCs structure.

  20. Targeted Delivery of Chemotherapeutic Agents Using Improved Radiosensitive Liquid Core Microcapsules and Assessment of Their Antitumor Effect

    SciTech Connect

    Harada, Satoshi Ehara, Shigeru; Ishii, Keizo; Yamazaki, Hiromichi; Matsuyama, Shigeo; Sato, Takahiro; Oikawa, Shyoichi; Kamiya, Tomihiro; Arakawa, Kazuo; Yokota, Wataru; Sera, Koichiro; Ito, Jyun

    2009-10-01

    Purpose: Radiation-sensitive microcapsules composed of alginate and hyaluronic acid are being developed. We report the development of improved microcapsules that were prepared using calcium- and yttrium-induced polymerization. We previously reported on the combined antitumor effect of carboplatin-containing microcapsules and radiotherapy. Methods and Materials: We mixed a 0.1% (wt/vol) solution of hyaluronic acid with a 0.2% alginate solution. Carboplatin (l mg) and indocyanine green (12.5 {mu}g) were added to this mixture, and the resultant material was used for capsule preparation. The capsules were prepared by spraying the material into a mixture containing a 4.34% CaCl{sub 2} solution supplemented with 0-0.01% yttrium. These capsules were irradiated with single doses of 0.5, 1.0, 1.5, or 2 Gy {sup 60}Co {gamma}-rays. Immediately after irradiation, the frequency of microcapsule decomposition was determined using a microparticle-induced X-ray emission camera. The amount of core content released was estimated by particle-induced X-ray emission and colorimetric analysis with 0.25% indocyanine green. The antitumor effect of the combined therapy was determined by monitoring its effects on the diameter of an inoculated Meth A fibrosarcoma. Results: Microcapsules that had been polymerized using a 4.34% CaCl{sub 2} solution supplemented with 5.0 x 10{sup -3}% (10{sup -3}% meant or 10%{sup -3}) yttrium exhibited the maximal decomposition, and the optimal release of core content occurred after 2-Gy irradiation. The microcapsules exhibited a synergistic antitumor effect combined with 2-Gy irradiation and were associated with reduced adverse effects. Conclusion: The results of our study have shown that our liquid core microcapsules can be used in radiotherapy for targeted delivery of chemotherapeutic agents.

  1. Development of stable flaxseed oil emulsions as a potential delivery system of ω-3 fatty acids.

    PubMed

    Goyal, Ankit; Sharma, Vivek; Upadhyay, Neelam; Singh, A K; Arora, Sumit; Lal, Darshan; Sabikhi, Latha

    2015-07-01

    The objective of the present study was to develop a stable flaxseed oil emulsion for the delivery of omega-3 (ω-3) fatty acids through food fortification. Oil-in-water emulsions containing 12.5 % flaxseed oil, 10 % lactose and whey protein concentrate (WPC)-80 ranging from 5 to 12.5 % were prepared at 1,500, 3,000 and 4,500 psi homogenization pressure. Flaxseed oil emulsions were studied for its physical stability, oxidative stability (peroxide value), particle size distribution, zeta (ζ)-potential and rheological properties. Emulsions homogenized at 1,500 and 4,500 psi pressure showed oil separation and curdling of WPC, respectively, during preparation or storage. All the combinations of emulsions (homogenized at 3,000 psi) were physically stable for 28 days at 4-7 ºC temperature and did not show separation of phases. Emulsion with 7.5 % WPC showed the narrowest p