31
views
0
recommends
+1 Recommend
1 collections
    0
    shares

      International Journal of Nanomedicine (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the application of nanotechnology in diagnostics, therapeutics, and drug delivery systems throughout the biomedical field. Sign up for email alerts here.

      105,621 Monthly downloads/views I 7.033 Impact Factor I 10.9 CiteScore I 1.22 Source Normalized Impact per Paper (SNIP) I 1.032 Scimago Journal & Country Rank (SJR)

      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Comparative toxicological assessment of PAMAM and thiophosphoryl dendrimers using embryonic zebrafish

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Dendrimers are well-defined, polymeric nanomaterials currently being investigated for biomedical applications such as medical imaging, gene therapy, and tissue targeted therapy. Initially, higher generation (size) dendrimers were of interest because of their drug carrying capacity. However, increased generation was associated with increased toxicity. The majority of studies exploring dendrimer toxicity have focused on a small range of materials using cell culture methods, with few studies investigating the toxicity across a wide range of materials in vivo. The objective of the present study was to investigate the role of surface charge and generation in dendrimer toxicity using embryonic zebrafish ( Danio rerio) as a model vertebrate. Due to the generational and charge effects observed at the cellular level, higher generation cationic dendrimers were hypothesized to be more toxic than lower generation anionic or neutral dendrimers with the same core composition. Polyamidoamine (PAMAM) dendrimers elicited significant morbidity and mortality as generation was decreased. No significant adverse effects were observed from the suite of thiophosphoryl dendrimers studied. Exposure to ≥50 ppm cationic PAMAM dendrimers G3-amine, G4-amine, G5-amine, and G6-amine caused 100% mortality by 24 hours post-fertilization. Cationic PAMAM G6-amine at 250 ppm was found to be statistically more toxic than both neutral PAMAM G6-amidoethanol and anionic PAMAM G6-succinamic acid at the same concentration. The toxicity observed within the suite of varying dendrimers provides evidence that surface charge may be the best indicator of dendrimer toxicity. Dendrimer class and generation are other potential contributors to the toxicity of dendrimers. Further studies are required to better understand the relative role each plays in driving the toxicity of dendrimers. To the best of our knowledge, this is the first in vivo study to address such a broad range of dendrimers.

          Most cited references47

          • Record: found
          • Abstract: found
          • Article: not found

          Dendrimer-encapsulated metal nanoparticles: synthesis, characterization, and applications to catalysis.

          This Account reports the synthesis and characterization of dendrimer-encapsulated metal nanoparticles and their applications to catalysis. These materials are prepared by sequestering metal ions within dendrimers followed by chemical reduction to yield the corresponding zerovalent metal nanoparticle. The size of such particles depends on the number of metal ions initially loaded into the dendrimer. Intradendrimer hydrogenation and carbon-carbon coupling reactions in water, organic solvents, biphasic fluorous/organic solvents, and supercritical CO2 are also described.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Dendrimers in drug research.

            Dendrimers are versatile, derivatisable, well-defined, compartmentalised chemical polymers with sizes and physicochemical properties resembling those of biomolecules e.g. proteins. The present critical review (citing 158 references) briefly describes dendrimer design, nomenclature and divergent/convergent dendrimer synthesis. The characteristic physicochemical features of dendrimers are highlighted, showing the effect of solvent pH and polarity on their spatial structure. The use of dendrimers in biological systems are reviewed, with emphasis on the biocompatibility of dendrimers, such as in vitro and in vivo cytotoxicity, as well as biopermeability, biostability and immunogenicity. The review deals with numerous applications of dendrimers as tools for efficient multivalent presentation of biological ligands in biospecific recognition, inhibition and targeting. Dendrimers may be used as drugs for antibacterial and antiviral treatment and have found use as antitumor agents. The review highlights the use of dendrimers as drug or gene delivery devices in e.g. anticancer therapy, and the design of different host-guest binding motifs directed towards medical applications is described. Other specific examples are the use of dendrimers as 'glycocarriers' for the controlled multimeric presentation of biologically relevant carbohydrate moieties which are useful for targeting modified tissue in malignant diseases for diagnostic and therapeutic purposes. Finally, the use of specific types of dendrimers as scaffolds for presenting vaccine antigens, especially peptides, for use in vaccines is presented.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Dendrimer toxicity: Let's meet the challenge.

              Dendrimers are well-defined, versatile polymeric architecture with properties resembling biomolecules. Dendritic polymers emerged as outstanding carrier in modern medicine system because of its derivatisable branched architecture and flexibility in modifying it in numerous ways. Dendritic scaffold has been found to be suitable carrier for a variety of drugs including anticancer, anti-viral, anti-bacterial, antitubercular etc., with capacity to improve solubility and bioavailability of poorly soluble drugs. In spite of extensive applicability in pharmaceutical field, the use of dendrimers in biological system is constrained because of inherent toxicity associated with them. This toxicity is attributed to the interaction of surface cationic charge of dendrimers with negatively charged biological membranes in vivo. Interaction of dendrimers with biological membranes results in membrane disruption via nanohole formation, membrane thinning and erosion. Dendrimer toxicity in biological system is generally characterized by hemolytic toxicity, cytotoxicity and hematological toxicity. To minimize this toxicity two strategies have been utilized; first, designing and synthesis of biocompatible dendrimers; and second, masking of peripheral charge of dendrimers by surface engineering. Biocompatible dendrimers can be synthesized by employing biodegradable core and branching units or utilizing intermediates of various metabolic pathways. Dendrimer biocompatibility has been evaluated in vitro and in vivo for efficient presentation of biological performance. Surface engineering masks the cationic charge of dendrimer surface either by neutralization of charge, for example PEGylation, acetylation, carbohydrate and peptide conjugation; or by introducing negative charge such as half generation dendrimers. Neutral and negatively charged dendrimers do not interact with biological environment and hence are compatible for clinical applications as elucidated by various studies examined in this review. Chemical modification of the surface is an important strategy to overcome the toxicity problems associated with the dendrimers. The present review emphasizes on the approaches available to overcome the cationic toxicity inherently associated with the dendrimers. Copyright (c) 2010 Elsevier B.V. All rights reserved.
                Bookmark

                Author and article information

                Journal
                Int J Nanomedicine
                Int J Nanomedicine
                International Journal of Nanomedicine
                Dove Medical Press
                1176-9114
                1178-2013
                2014
                17 April 2014
                : 9
                : 1947-1956
                Affiliations
                [1 ]Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR, USA
                [2 ]School of Chemical, Biological, and Environmental Engineering, Oregon State University, Corvallis, OR, USA
                Author notes
                Correspondence: Stacey L Harper, Oregon State University, 1007 Agriculture and Life Sciences Building, Corvallis, Oregon 97331, USA, Tel +1 541 737 2791, Fax +1 541 737 0497, Email stacey.harper@ 123456oregonstate.edu
                Article
                ijn-9-1947
                10.2147/IJN.S60220
                4000179
                24790436
                a59e82dc-fba7-439b-9862-5c6dd373b9d9
                © 2014 Pryor et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License

                The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Original Research

                Molecular medicine
                nanomaterials,in vivo,toxicity,generation,surface chemistry,zebrafish
                Molecular medicine
                nanomaterials, in vivo, toxicity, generation, surface chemistry, zebrafish

                Comments

                Comment on this article