New class of squalene-based releasable nanoassemblies of paclitaxel, podophyllotoxin, camptothecin and epothilone A

Eur J Med Chem. 2014 Oct 6:85:179-90. doi: 10.1016/j.ejmech.2014.07.035. Epub 2014 Jul 27.

Abstract

The present study reports the preparation of a novel class of squalene conjugates with paclitaxel, podophyllotoxin, camptothecin and epothilone A. The obtained compounds are characterized by a squalene tail that makes them able to self-assemble in water, and by a drug unit connected via a disulfide-containing linker to secure the release inside the cell. All the obtained compounds were effectively able to self-assemble and to release the parent drug in vitro. Disulfide-containing paclitaxel-squalene derivative showed a similar biological activity when compared to the free drug. Immunofluorescence assay shows that this squalene conjugate enters A549 cells and stain microtubule bundles. The results described herein pave the way for different classes of squalene-based releasable nanoassemblies.

Keywords: Camptothecin; Epothilone A; Nanoassemblies; Paclitaxel; Podophyllotoxin; Squalene derivatives.

MeSH terms

  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Camptothecin / chemistry
  • Camptothecin / pharmacology
  • Cell Line, Tumor
  • Drug Carriers / chemistry
  • Drug Liberation*
  • Epothilones / chemistry
  • Epothilones / pharmacology
  • Humans
  • MCF-7 Cells
  • Microtubules / drug effects
  • Nanostructures / chemistry*
  • Paclitaxel / chemistry
  • Paclitaxel / pharmacology
  • Podophyllotoxin / chemistry
  • Podophyllotoxin / pharmacology
  • Squalene / chemistry*

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Epothilones
  • epothilone A
  • Squalene
  • Podophyllotoxin
  • Paclitaxel
  • Camptothecin