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The “squalenoylation” an original plateform for the discovery of new, safer and more efficient nanomedicines

Référence

86367-01

Statut des brevets

French priority patent application n°0451365 filed on June 30, 2004 and entitled “Nanoparticules de dérivés de la gemcitabine”

Inventeurs

Patrick COUVREUR
Barbara STELLA
Flavio ROCCO
Véronique ROSILIO
Jack-Michel RENOIR
Luigi CATTEL

Statut commercial

Exclusive or non exclusive licenses

Laboratoire

Institut GALIEN (UMR8612), Chatenay-Malabry, France

Description

Although the introduction of nanotechnology in pharmacology (“œnanomedicine”) has revolutionized the delivery of drugs, it is certain that only few nanomedicines have reached clinical stage and market. These failures are due to: (i) Poor drug loading, which is usually less than 5% (weight % of the transported drug with respect to the carrier material). As a result, either the quantity of the drug administered is not sufficient to reach a pharmacologically active concentration in the body, or the amount of the carrier material required is too large, leading to toxicity, (ii) the rapid uncontrolled release (ie. “burst release”) of the encapsulated drug after administration and (iii) the difficulty of designing synthetic materials  which combine low toxicity, biodegradability and do not accumulate in cells or tissues.  In this context, the team has developed the breakthrough concept of “œsqualenoylation”.

TECHNICAL DESCRIPTION

We have discovered that the linkage of squalene, a natural and biocompatible lipid, to anticancer and antimicrobial drugs permitted the spontaneous formation of nanoassemblies with dramatically increased pharmacological activity, comparatively to the parent drugs. In other words, our concept is to form the nanomedicine by self-aggregation of the bioconjugate itself without the need of any other transporter material. This approach is unique and has never been used before. It allows to dramatically increase the nanoparticle drug load and to avoid the so called “œburst release” due to the chemical linkage which may, in addition, be sensitive to specific intracellular enzymes.

DEVELOPMENT STAGE

  • Synthesis and characterization of squalene-based nanomedicines
  • In vivo efficacy assays (pre-clinical)
  • Lead optimization (gemcitabine squalene and doxorubicine-squalene

BENEFITS

The squalenoylated nanomedicines are able: (i) to protect the drug from degradation, (ii) to enhance drug’s intracellular penetration and (iii) to control drug release and biodistribution.

INDUSTRIAL APPLICATIONS

The proof of concept has already been done with anticancer (ie. gemcitabine, doxorubicine and cis-platine) and antiinfectious (ie. penicillin, AZT) drugs. This approach should accelerate the discovery of new treatments for severe diseases.

For further information, please contact us (Ref 86367-01)

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