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

• We previously reported the ability of disulfide-containing bivalent compounds to release active drugs.
• We envisioned the possibility to prepare a novel class of disulfide-containing squalene conjugates.
• We describe the synthesis of new class of conjugates, the formation and the characterization of the nanoassemblies.
• We demonstrate their ability to release the drug unit.
• We indirectly demonstrate for compound 12a (paclitaxel derivative) the capacity to permeate the cell membrane.

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.

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