11 research outputs found

    Pharmaceutical characterization of solid and dispersed carbon nanotubes as nanoexcipients

    No full text
    Marina V Ivanova1, Constanze Lamprecht1, M Jimena Loureiro1, J Torin Huzil1,2, Marianna Foldvari11School of Pharmacy, 2Faculty of Applied Mathematics, University of Waterloo, Waterloo, ON, CanadaBackground: Carbon nanotubes (CNTs) are novel materials with considerable potential in many areas related to nanomedicine. However, a major limitation in the development of CNT-based therapeutic nanomaterials is a lack of reliable and reproducible data describing their chemical and structural composition. Knowledge of properties including purity, structural quality, dispersion state, and concentration are essential before CNTs see widespread use in in vitro and in vivo experiments. In this work, we describe the characterization of several commercially available and two in-house-produced CNT samples and discuss the physicochemical profiles that will support their use in nanomedicine.Methods: Eighteen single-walled and multi-walled CNT raw materials were characterized using established analytical techniques. Solid CNT powders were analyzed for purity and structural quality using thermogravimetric analysis and Raman spectroscopy. Extinction coefficients for each CNT sample were determined by ultraviolet-visible near infrared absorption spectroscopy. Standard curves for each CNT sample were generated in the 0–5 µg/mL concentration range for dispersions prepared in 1,2-dichlorobenzene.Results: Raman spectroscopy and thermogravimetric analysis results demonstrated that CNT purity and overall quality differed substantially between samples and manufacturer sources, and were not always in agreement with purity levels claimed by suppliers. Absorbance values for individual dispersions were found to have significant variation between individual single-walled CNTs and multi-walled CNTs and sources supplying the same type of CNT. Significant differences (P < 0.01) in extinction coefficients were observed between and within single-walled CNTs (24.9–53.1 mL•cm-1•mg-1) and multi-walled CNTs (49.0–68.3 mL•cm-1•mg-1). The results described here suggest a considerable role for impurities and structural inhomogeneities within individual CNT preparations and the resulting spectroscopic properties of their dispersions.Conclusion: Raw CNT materials require thorough analytical workup before they can be used as nanoexcipients. This applies especially to the determination of CNT purity, structure, and concentration. The results presented here clearly demonstrate that extinction coefficients must be determined for individual CNT preparations prior to their use.Keywords: carbon nanotubes, pharmaceutical characterization, Raman spectroscopy, thermogravimetric analysis, ultraviolet-visible near infrared spectroscop

    Microtubule targeting agents: from biophysics to proteomics

    Full text link
    This review explores various aspects of the interaction between microtubule targeting agents and tubulin, including binding site, affinity, and drug resistance. Starting with the basics of tubulin polymerization and microtubule targeting agent binding, we then highlight how the three-dimensional structures of drug-tubulin complexes obtained on stabilized tubulin are seeded by precise biological and biophysical data. New avenues opened by thermodynamics analysis, high throughput screening, and proteomics for the molecular pharmacology of these drugs are presented. The amount of data generated by biophysical, proteomic and cellular techniques shed more light onto the microtubule-tubulin equilibrium and tubulin-drug interaction. Combining these approaches provides new insight into the mechanism of action of known microtubule interacting agents and rapid in-depth characterization of next generation molecules targeting the interaction between microtubules and associated modulators of their dynamics. This will facilitate the design of improved and/or alternative chemotherapies targeting the microtubule cytoskeleton

    Microtubule-binding agents: a dynamic field of cancer therapeutics.

    No full text
    International audienceMicrotubules are dynamic filamentous cytoskeletal proteins composed of tubulin and are an important therapeutic target in tumour cells. Agents that bind to microtubules have been part of the pharmacopoeia of anticancer therapy for decades and until the advent of targeted therapy, microtubules were the only alternative to DNA as a therapeutic target in cancer. The screening of a range of botanical species and marine organisms has yielded promising new antitubulin agents with novel properties. In the current search for novel microtubule-binding agents, enhanced tumour specificity, reduced neurotoxicity and insensitivity to chemoresistance mechanisms are the three main objectives
    corecore