Blanc Inter II - SIMI 8 - Blanc International II - SIMI 8 - Chimie du solide, colloïdes, physicochimie

Microwave assisted Milligel synthesis under continuous Flow – MIMIFLOW

MIMIFLOW

Novel dosage forms of active species are strongly demanded for drug delivery. Polymer-based drug depots, which degrade in-vivo during a predefined time and dose are a promising strategy and will be investigated in MIMIFLOW. The syntheses will be performed in microwave reactors, with a dedicated focus on millifluidic continuous-flow systems in order to produce polymer networks with defined shapes and geometries for their specific applications.

MIMIFLOW : challenges and objectives

For the successful of this project, two french laboratories (IPREM and LOF) and one austrian laboratory (ICTM) will join their competencies and participate to MIMIFLOW. <br />One of the innovative aspects will be to go from macrogels in batch and conventional heating to the synthesis of milligel in continuous flow and under MW irradiation. Regardless of the exact nature of the still debated microwave effects microwave synthesis is an established process to increase yields, purity, reaction rates. On the other hand, fluidic synthesis has recently offered a promising approach to the continuous production of polymer particles with unprecedented control over their sizes, shapes and morphologies. MIMIFLOW aims developing a specific device able to be inserted within the microwave reactor cavity. Polymer particles exhibiting exceptional low polydispersity are expected without any viscosity constraint. Cytotoxicity tests of the polymer networks as well as the corresponding degradation products will be performed in order to validate the usage of this novel class of copolymers as drug depots. <br />

For the successful of this project, two french laboratories (IPREM and LOF) and one austrian laboratory (ICTM) will join their competencies and participate to MIMIFLOW in terms of :
-Microwave synthesis: The development of polymer chemistry under microwave irradiation remains slower than in organic chemistry. Nevertheless, IPREM already showed significant polymerization results and developed the continuous polymerization under microwave irradiation in collaboration with the LOF. On the other hand ICTM obtained polyoxazoline using micowaves with unexpected polymerization rate and purity.
-- Droplet-based fluidics: LOF and IPREM lead to an innovative concept in polymer synthesis under microwave irradiation: the increase in viscosity due to the polymerization reaction is now confined inside the droplet, and the small scale allows a good control of the penetration depth of the MWs.
-Milligel synthesis: MIMIFLOW is dedicated to the optimization of the synthesis of bio-compatible gels and will be based on the preliminary results of ICTM on network synthesis and of IPREM on gel properties characterization.

MIMIFLOW will develop a new device for the continuous milligel synthesis under microwave irradiation. Polymer-based drug depots, which degrade in-vivo during a predefined time and constantly release the drugs required by the patients in the recommended dose.


Mimiflow has the ambition to support the research made in Europe and particularly in France and Austria through a program in the field of the chemistry and processes under microwave irradiation.
The aim of this project is to develop a new assisted microwave synthesis of milligel under continuous flow. These polymers will be characterized as hybrid networks for drug release.
MIMIFLOW will develop a new device for the continuous polymer synthesis under microwave irradiation.
MIMIFLOW will offer the development of an innovative concept to obtain polymer gel particle under microwaves and continuous flow.
MIMIFLOW will focus on poly(2-oxazoline)s having a distinct potential in terms of biocompatibility, degradability, high stability and the lack of toxic by-products produced during degradation as compared to the commonly known poly(ethylene glycol) PEG. Moreover, poly(2-oxazoline)s show similar retention times to PEG within the blood and major organs. The class of hybrid polymers composed of poly(2-oxazoline)s and poly(ester)s have been focused on only during the most recent years.
The innovative gels, perfomed within MIMIFLOW project, will be characterized and tested as drug-depot. Novel dosage forms of pharmaceutically active components are strongly demanded because of the demographic European change. It is crucial to develop an efficient medication to maintain older-aged individuals independent, which represent an advantage of an economic and social point of view.

As soon as possible, project results will be disseminated primarily by publications in leading international journals.
The results will also be presented at major international conferences that , for example, focus on the use of enabling technologies in synthetic chemistry including microwave and continuous flow processing.

Novel dosage forms of pharmaceutically active components are strongly demanded for abuse-free application of drugs as well as by the demographic change, which has added high levels of importance to easy-to-use medication in order to leave older-aged individuals independent of nursery as long as possible. Polymer-based drug depots, which degrade in-vivo during a predefined time and constantly release the drugs required by the patients in the recommended dose, are a promising strategy to aid in this concern that will be investigated in the project “MIMIFLOW: Microwave-Assisted Milligel Synthesis under Continuous Flow”, a collaboration of the University of Pau, the National Center of Scientific Research in Pessac, and the Graz University of Technology.
The aim of this project is the development of novel polymer carrier matrices based on crosslinked biopolyesters and poly(2-oxazoline)s. These polymer networks are assigned high potential to combine the advantages of both types of polymers involved and to overcome their respective limitations like too slow degradation kinetics, hydrophobicity, or bulk erosion. In order to correlate the networks’ properties with their structures and to allow for tailor-made material fabrication from “desktop calculations”, three-dimensional libraries of poly(ester-oxazoline)s will be synthesized. Drug inclusion will be performed in two alternative ways, either by in-situ inclusion during the polymerization or from post-synthetic swelling/diffusion/drying cycles of the polymers. In particular the latter approach will aim at the development of “carrier” materials that can be loaded with individual medication in order to yield personalized drug carriers. These drug carriers will be designed in a way that they degrade in-vivo and provide patients with constant drug levels, eliminating the risks of adroitness and mixed-up medications.
The syntheses will be performed in state-of-the-art microwave reactors, with a dedicated focus on millifluidic continuous-flow systems in order to produce poly(ester-oxazoline) networks with defined shapes and geometries for their specific applications. Contrary to the organic chemistry, the development of polymer chemistry under microwave irradiation is still slower. Regardless of the exact nature of the still debated microwave effects microwave synthesis is an established process to increase yields, purity, reaction rates. On the other hand, fluidic synthesis has recently offered a promising approach to the continuous production of polymer particles with unprecedented control over their sizes, shapes and morphologies. MIMIFLOW aims developing a specific device able to be inserted within the microwave reactor cavity. Polymer particles exhibiting exceptional low polydispersity are expected without any viscosity constraint.
Mechanical characterization of the polymer networks with and without drugs in the non-swollen and swollen state as well as the degradation and release kinetics will be determined. In particular the mechanical tests of the swollen specimens will be important for optimizing the materials’ properties for in-vivo applications. Cytotoxicity tests of the polymer networks as well as the corresponding degradation products will be performed in order to validate the usage of this novel class of copolymers as drug depots.
At the end of the MIMIFLOW project, biodegradable poly(ester-oxazoline) networks will have been synthesized and characterized by wettability, swelling degrees, mechanical properties in the dry and swollen state and degradation / release kinetics. Representative candidates will have been in-vitro tested for applicability in mammalian bodies and their functionality as drug depots.

Project coordinator

Madame Stephanie Reynaud (Institut des sciences analytiqueset de physicochimie pour l'environnement et les matériaux) – stephanie.reynaud@univ-pau.fr

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

ICMT ICMT
LOF, UMR 5258 Laboratoire du Futur
IPREM, UMR 5254 Institut des sciences analytiqueset de physicochimie pour l'environnement et les matériaux

Help of the ANR 310,960 euros
Beginning and duration of the scientific project: February 2013 - 42 Months

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