● Affiliated research Laboratories:
-
Laboratoire de Mécanique, Modélisation & Procédés Propres – M2P2 –
UMR 7340, AMU, CNRS, Centrale Marseille, Technopôle
de l’Arbois, 13545 Aix-en-Provence
- Aix Marseille Univ, CNRS, INT, Inst Neurosci Timone, Marseille, France
- Centre Paradis Monticelli, 433 bis rue Paradis, 13008, Marseille
- A French pharmaceutical group
● Doctoral research subject:
The
development of intravitreal sustained-release drug delivery systems of
anti-vascular endothelial growth factor (anti-VEGF) antibodies is a
challenging issue in the treatment of macular degeneration and diabetic
macular edema. Indeed, even if the introduction of anti-VEGF therapy
through intravitreal injection has revolutionized the corresponding
treatments, they remain limited by the necessity of monthly injections
which limits the patient observance and increases complication risks
(retinal detachment, endophthalmitis, and cataracts). Such drawbacks can
be overcome by the development of sustained release anti-VEGF delivery
systems that maintain a therapeutically relevant concentration of
protein drug for extended periods of time [1]. Nevertheless, processing
therapeutic antibodies through conventional technologies can be hindered
by their thermolability, their sensitivity to organic solvents and to
shear stresses. All those drawbacks can be avoided using supercritical
CO2 processes.
The originality of
this research project is to develop innovative intravitreal
sustained-release medical devices while encapsulating anti-VEGF
antibodies with biocompatible excipients using the environment-friendly
CO2 supercritical technology.
This
technology is now recognized as a real alternative of conventional
techniques of drug processes using liquid organic solvents and has been
applied to drug formulation for the past 30 years. One of the most
interesting properties of supercritical CO2, is related notably to its
moderate critical temperature (Tc = 31°C) and easily accessible critical
pressure (Pc= 7.38 MPa), which allows the processing of thermosensitive
molecules. Being gaseous at ambient conditions, CO2 separation from the
end-products is spontaneous upon depressurization. There is no need for
the several stages of separation as in conventional processes, which
are costly and detrimental to thermosensitive molecules (as antibodies).
The resulting products from a single-step process exhibit more
homogeneous properties.
Furthermore,
supercritical fluids are characterized by specific properties,
intermediate between those of liquids and gases allowing to reduce, or
even to avoid the use of organic solvents. Those properties can be also
modulated by varying the pressure and temperature conditions. As a
result, supercritical fluid-based processes are characterized by favored
transfer phenomena and performances that cannot always be obtained by
conventional pharmaceutical formulation processes.
Even
if the supercritical technology has been successfully applied to a
hundred active pharmaceutical ingredients, several excipients as well as
to the development of composite formulations, few studies and processes
are applied to the encapsulation of antibodies, which supports the
innovative aspect of this research project.
This
project is a part of a collaboration between the research team
“Processes and Supercritical fluids” of the laboratory M2P2 (UMR CNRS
7340, Aix Marseille University), expert on pharmaceutical formulation
processes using supercritical fluids [2-7] and Pr. Matonti, expert in
the retina complications and diseases, affiliated to the Neuroscience
Institute of La Timône and to the Paradis Monticelli Center of
Ophthalmology and supported by a French pharmaceutical group. The
complementary skills and competences of involved partners, as well as
their geographical proximity, are all assets.
The
objective of this Ph.D. work will be to implement a new solvent-free
process so as to form innovative intravitreal sustained-release drug
delivery systems.
● Key words : Chemical Engineering, Supercritical fluids, Drug delivery systems, Encapsulation
● Doctoral research subject :
We
are seeking for an outstanding and motivated candidate with an
Engineer/Master’s degree in Chemical Engineering / Biomedical
Engineering / Industrial pharmacy.
The candidate would demonstrate
motivation, scientific curiosity and rigor. He/she should present good
experimental skills, autonomy and investment.
Experiences in supercritical fluid processes, galenic formulations and encapsulation processes are valuable.
A good command of English language (written and spoken) is required.
● Application:
A
covering letter, a detailed curriculum vitae, contact details of at
least two references and transcript of at least the two last years of
studies should be sent to:
yasmine.masmoudi@univ-amu.fr
elisabeth.badens@univ-amu.fr
References:
[1]
D.A. Eichenbaum, C. Buznego, C.Y. Weng, D.S. Dhoot, C.C. Wykoff, V.S.
Sheth, When and How to Incorporate Steroids for Persistent Diabetic
Macular Edema: A Discussion of Real-World Treatment Optimization
Strategies, Ophthalmic Surg Lasers Imaging Retina, 49(7), S5-S15, 2018.
[2]
E. Badens, Y. Masmoudi, A. Mouahid, C. Crampon, Current situation and
perspectives in drug formulation by using supercritical fluid
technology, The Journal of Supercritical Fluids, 134, 274-283, 2018.
[3]
J.M. Silva, S. Akkache, A. C. Araújo, Y. Masmoudi, R. L. Reis, E.
Badens, A.R.C. Duarte, Development of innovative medical devices by
dispersing fatty acid eutectic blend on gauzes using supercritical
particle generation processes, Materials Science and Engineering C, 99,
599-610, 2019.
[4] A. Bouledjouidja, Y. Masmoudi, Y.
Li, W. He, E. Badens, Supercritical impregnation and optical
characterization of loaded foldable intraocular lenses using
supercritical fluids, Journal of Cataract & Refractive Surgery, 43,
1343-1349, 2017.
[5] A. Bouledjouidja, Y. Masmoudi, M.
Sergent, E. Badens, Effect of operational conditions on the
supercritical carbon dioxide impregnation of anti-inflammatory and
antibiotic drugs in rigid commercial intraocular lenses, The Journal of
Supercritical Fluids, 130, 63–75, 2017.
[6] R. Djerafi,
A. Swanpaul, P. Labuschagne, M.L. Kalombo, E. Badens, C. Crampon, Y.
Masmoudi, Supercritical antisolvent co-precipitation of Rifampicin and
Ethyl cellulose, The European Journal of Pharmaceutical Sciences, 102,
161-171, 2017.
[7] J-M. Andre, E. Badens, O. Forzano,
Y. Masmoudi, Treatment process for producing implants or prostheses of
polymers for controlled release of active ingredients, Patent
WO/2014/037651, 2014.
