Subventions et des contributions :

Subvention ou bourse octroyée s'appliquant à plus d'un exercice financier. (2017-2018 à 2018-2019)

Design of self-assembling materials for challenging drug formulations and implant devices
The conceptual core of the proposed research is that “Minor modifications can generate Major changes” in certain self-assembling polymeric excipient features. Several polyhydroxylic materials may present strong interchain self-assembling stabilized by hydrogen association. Starch is a natural polysaccharide exhibiting different morphological forms - double helix (B type) or single helix (V type) that coexist with disordered regions. The V-type structures present a relatively hydrophobic inner surface that can hold iodine or even some fatty molecules. Among the current drugs, many of them are very low soluble (i.e. non-steroidal anti-inflammatory drugs, as ibuprofen) and consequently difficult to formulate for controlled delivery. Other drugs present a very high solubility (such as the antidiabetic metformin) and are also difficult to formulate for sustained release. Thus, their efficiency is low and they can produce undesirable side effects due to their liberation at improper sites.
One of the main objectives of our next 5 years research is to conceive new and challenging pharmaceutical forms of drugs known for the difficult formulation because of their too low or too high solubility.
Our hypothesis is that a proper derivatization could increase the inner cavity diameter of starch V-helices that may locate hydrophobic drugs. The Carboxymethyl(CM)-Starch, an anionic derivative charged with CM groups, is expected to present a cavity size larger than that of nonmodified Starch. Consequently CM-Starch can hold larger and more hydrophobic agents. A new form of an ampholytic Starch (CM-AE-Starch) carrying both anionic (CM) and cationic aminoethyl (AE) groups will be proposed as an excipient able to delay the release of drugs with absorption at lower intestine or at colon level. This ampholytic excipient is expected to present a self-stabilization not only by hydrogen associations, but also by ionic interactions and is aimed to formulate highly soluble agents (as Metformin).
A second main objective is to introduce novel biomaterials for tissue culture, for implants and xenografts (i.e aorta prosthesis) devices. Polyvinyl alcohol (PVA) polymers have been proven as acceptable biomaterials with interesting mechanical and film-forming characteristics due to its strong self-assembling capacity. However, previous reports showed a low colonisation of PVA devices and that certain implants of PVA generate signs of irritation and formation of fibrosis surrounding tissues. Chitosan was suggested to be associated with several biocompatible materials, but it presents a poor solubility and its applications may be limited. Our hypothesis is that association of CarboxyEthyl(CE)-Chitosan to PVA will generate biomaterials of interest for hepatocytes, for neurons or for implants and vascular grafts.