Biodistribution and pharmacokinetics of a telodendrimer micellar paclitaxel nanoformulation in a mouse xenograft model of ovarian cancer

Wenwu Xiao1, Juntao Luo2, Teesta Jain3, John Riggs3, Harry P Tseng1, Paul T Henderson3, Simon R Cherry4, Douglas Rowland4, Kit S Lam1,31Department of Biochemistry and Molecular Medicine, UC Davis Cancer Center, University of California Davis, Sacramento, CA; 2Department of Pharmacology, SUNY Upstate Cancer Research Institute, SUNY Upstate Medical University, Syracuse, NY; 3Department of Internal Medicine, Division of Hematology and Oncology, 4Department of Biomedical Engineering, UC Davis Cancer Center, University of California Davis, Davis, CABackground: A multifunctional telodendrimer-based micelle system was characterized for delivery of imaging and chemotherapy agents to mouse tumor xenografts. Previous optical imaging studies demonstrated qualitatively that these classes of nanoparticles, called nanomicelles, preferentially accumulate at tumor sites in mice. The research reported herein describes the detailed quantitative imaging and biodistribution profiling of nanomicelles loaded with a cargo of paclitaxel.Methods: The telodendrimer was covalently labeled with 125I and the nanomicelles were loaded with 14C-paclitaxel, which allowed measurement of pharmacokinetics and biodistribution in the mice using microSPECT/CT imaging and liquid scintillation counting, respectively.Results: The radio imaging data showed preferential accumulation of nanomicelles at the tumor site along with a slower clearance rate than paclitaxel formulated in Cremophor EL (Taxol®). Liquid scintillation counting confirmed that 14C-labeled paclitaxel sequestered in nanomicelles had increased uptake by tumor tissue and slower pharmacokinetics than Taxol.Conclusion: Overall, the results indicate that nanomicelle-formulated paclitaxel is a potentially superior formulation compared with Taxol in terms of water solubility, pharmacokinetics, and tumor accumulation, and may be clinically useful for both tumor imaging and improved chemotherapy applications.Keywords: telodendrimer, nanomicelle, paclitaxel, microSPECT/CT, imaging guided drug deliver

Solubilization of Proteins in 2DE: An Outline

Protein solubilization for two-dimensional electrophoresis (2DE) has to break molecular interactions to separate the biological contents of the material of interest into isolated and intact polypeptides. This must be carried out in conditions compatible with the first dimension of 2DE, namely isoelectric focusing. In addition, the extraction process must enable easy removal of any nonprotein component interfering with the isoelectric focusing. The constraints brought in this process by the peculiar features of isoelectric focusing are discussed, as well as their consequences in terms of possible solutions and limits for the solubilization process

“Obscure” references: a cautionary tale

[ES] Several concepts that have come to be significant in the interpretation of landforms and landscapes were first published in obscure local outlets, mentioned in passing, or tucked away in a large tome or in a footnote or appendix, before being revived or discovered anew and developed as part of the geomorphological canon. In some instances, the observations that led to new concepts were first aired decades or even centuries ago. But a new idea is a new idea, whenever it was discovered. Although the importance of testing and corroboration is not denied, natural justice surely calls for the recognition of those with whom the first glimmer of the various concepts originated.[EN] Algunos conceptos que han llegado a ser importantes para la interpretación de las formas del relieve y del paisaje fueron publicados por primera vez en medios locales y de forma poco clara, mencionados de pasada, o aparecen recogidos en algún volumen o en alguna nota al pie o apéndice, antes de ser redescubiertos de nuevo e incorporados como parte de los cánones geomorfológicos. En algunos casos, las observaciones que han llevado al establecimiento de nuevos conceptos fueron expuestas hace decenas o incluso cientos de años. Pero una nueva idea es siempre una nueva idea, independientemente de la época en que se descubra. Aunque no se niega la importancia de la experimentación y de la confirmación de los hechos, la justicia natural nos llama a reconocer a aquellos que, por primera vez, vislumbraron los diversos conceptos que han sido establecidos