CONTEXT

To date, despite several leading studies aimed at orally administering coupounds sensitive to the conditions of the gastrointestinal tract (pH, mechanical stress, various enzymatic attacks), it has not been possible to satisfactorily combine the comfort and more physiological way of taking a medicament orally with the advantages of administration by injection (absence or small amount of denaturation or degradation of the active ingredient, rapid action in view of its instantaneous availability in the blood).

In an attempt to solve this problem, research team has developped a potential complex vector adpted to oral delivery of active ingredients.

TECHNICAL DESCRIPTION

This invention concerns the encapsulation of active molecules, particularly peptides and proteins, into complex nanoparticles sized betweeen 50 and 250 nm suitable for oral delivery.

The inventors have defined a formulation concept consisting of complex vector based on these nanoparticles dispersed in appropriate media. This dispersion is introduced in a special carrier allowing the protection of the said nanoparticles, and thus the active molecule, through the transit in mouth and stomach from acid and enzymatic attacks. This carrier allows also the liberation of the nanoparticles loaded with active ingredient, in the intestine stream before being able to reach the bloodstream by passing the intestinal mucosa.

This system had been tested and validated with two active molecules:

• oral delivery of insulin which is currently administered subcutaneously,
• oral administration of peptide P140, a drug that specifically modulates the immune system of Lupus erythematosus patients. This drug (Lupuzorâ„¢) is in the III clinical trial stage, has been developped by CNRS laboratory (UPR9021) and licensed to Immupharma. It has been sublicensed to Cephalon Inc. by ImmuPharma in 2009.

STAGE OF DEVELOPMENT

The inventors have optimized the process of obtaining the nanoparticles with yield of 75% in P140 incorporation into these nanonparticles.

• in vitro efficacy assays:

The crossing of the nanoparticles through intestinal mucosa had been shown by using Caco-2 cell model. In addition to their presence on surface of these cells, the nanoparticles had been observed in cytoplasm and in intestinal basal membrane.

• preliminary in vivo efficacy assays:

The administration of these nanoparticles by intraduodenal way to lupic mice showed a conservation of P140 efficacy which appears to be similar with the one obtained by its classical intravenous administration. Death of these mice is delayed in time, proof of efficacy and bioavailability of P140 orally delivered.

With current experiments on mice, the team has obtained availability ranging from 20 to 30% of the whole administered insulin.

BENEFITS

This new oral delivery system resolves the problems linked to the degradation of active molecules in the gastrointestinal tract and their bioavailability. The innovative particularity of the present vector relates mainly to the ability of nanoparticles to pass into the intestinal mucosa and the liberation of active molecules directly in the bloodstream, not only in intestinal sphere, which enhance the bioavailability of the active molecule.

Moreover, oral delivery of active compounds is considered more physiological and more comfortable contrary to administration by injection which still being one of the most commonly used but consists on an invasive method and not always readily accepted by patients.

INDUSTRIAL APPLICATIONS

This technology provides us an original system for oral administration of pharmacologically active substances.

More particularly, this invention is intended to facilitate the delivery of P140 for the treatment of Lupus erythematosus. It may also improve patient compliance in the treatment of diabetes types 1.

For further information, please contact us (Ref 85966-01 / 85966-02)