In vitro behavior of multifunctionalized fullerene-warfarin conjugates.

In this study we have covalently linked the anticoagulant warfarin to polyfunctionalized fullerenes. The objective was to explore the possibility of modifying the biological profile of a drug by covalent binding to functionalized fullerene. We have chosen warfarin as a model compound because it a widely used drug. We have analyzed the stability in vitro of the conjugates and found that the drug is released from the carbon support only after incubation in mouse plasma.

Functionalized carbon nanotubes as emerging nanovectors for the delivery of therapeutics.

Functionalized carbon nanotubes (f-CNT) are emerging as a new family of nanovectors for the delivery of different types of therapeutic molecules. The application of CNT in the field of carrier-mediated delivery has become possible after the recent discovery of their capacity to penetrate into the cells. CNT can be loaded with active molecules by forming stable covalent bonds or supramolecular assemblies based on noncovalent interactions. Once the cargos are carried into various cells, tissues and organs they are able to express their biological function. In this review, we will describe the potential of f-CNT to deliver different types of therapeutic molecules.

Multifunctionalised cationic fullerene adducts for gene transfer: design, synthesis and DNA complexation.

Cationic poly-N,N-dimethylfulleropyrrolidinium derivatives have been designed and synthesised to complex plasmid DNA for gene delivery.

[60]fullerene-pyrrolidine-N-oxides.

Eight members of a new family of fullerene derivatives, [60]fulleropyrrolidine-N-oxides, have been synthesized and characterized. Facile oxidation, by a peracid, of the parent [60]fulleropyrrolidine gave clean conversions into the product molecules, in which the tertiary amine is transformed into a quaternary amine bearing an oxygen atom. The reaction is very selective, favoring the nitrogen atom of the pyrrolidine ring in preference to epoxidation of the fullerene cage. The 1H NMR shows an AB quartet splitting pattern, characteristic of nonequivalent hydrogens in the pyrrolidine ring and at a chemical shift displacement of 0.8 ppm downfield. Other methods of characterization are described, including MS, differential scanning calorimetry, thermogravimetric analysis, HPLC, UV/vis, and IR. Conclusive evidence for the formation of an N-oxide moiety is provided by the synthesis, oxidation, and NMR characterization of a novel [60]fulleropyrrolidine containing a 15N isotope, showing an 85 ppm downfield heteroatom chemical shift. Preliminary details of the effects of substitution on the reactivity of the pyrrolidine ring are also reported.

Tissue biodistribution and blood clearance rates of intravenously administered carbon nanotube radiotracers.

Carbon nanotubes (CNT) are intensively being developed for biomedical applications including drug and gene delivery. Although all possible clinical applications will require compatibility of CNT with the biological milieu, their in vivo capabilities and limitations have not yet been explored. In this work, water-soluble, single-walled CNT (SWNT) have been functionalized with the chelating molecule diethylentriaminepentaacetic (DTPA) and labeled with indium ((111)In) for imaging purposes. Intravenous (i.v.) administration of these functionalized SWNT (f-SWNT) followed by radioactivity tracing using gamma scintigraphy indicated that f-SWNT are not retained in any of the reticuloendothelial system organs (liver or spleen) and are rapidly cleared from systemic blood circulation through the renal excretion route. The observed rapid blood clearance and half-life (3 h) of f-SWNT has major implications for all potential clinical uses of CNT. Moreover, urine excretion studies using both f-SWNT and functionalized multiwalled CNT followed by electron microscopy analysis of urine samples revealed that both types of nanotubes were excreted as intact nanotubes. This work describes the pharmacokinetic parameters of i.v. administered functionalized CNT relevant for various therapeutic and diagnostic applications.

From a total synthesis of cepabactin and its 3:1 ferric complex to the isolation of a 1:1:1 mixed complex between iron (III), cepabactin and pyochelin.

A novel and straightforward total synthesis of cepabactin and its iron (III) complex is described. The latter compound was compared and identified to that obtained from the cultures of Burkholderia cepacia. On treatment of the growth medium of two different strains of B. cepacia with ferric chloride, we have isolated and characterized an unexpected mixed complex of iron (III), cepabactin and pyochelin.