Design of self-assembling materials for challenging drug formulations and cell-culture devices

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Design of self-assembling materials for challenging drug formulations and cell culture 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 be stabilized by strong interchain hydrogen association and self-assembling processes. Starch is a natural polysaccharide presenting double helix (B type) or single helix (V type) morphological forms that coexist with disordered regions. The V-type helix structures present a moderately hydrophobic inner surface that can hold iodine or even some fatty molecules. Among the current drugs, some of them are very low soluble (i.e. non-steroidal anti-inflammatory drugs, as ibuprofen) and thus 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, causing low efficiency and undesirable side effects due to their liberation at improper sites. ***A major objective of this research is to conceive new and challenging pharmaceutical forms of drugs which are known as difficult to formulate because of their too low or too high solubility. ***Our hypothesis is that a proper derivatization could increase the diameter of the inner cavity 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 ampholytic Starch, the CM-AE-Starch, carrying both anionic (CM) and cationic aminoethyl (AE) groups is proposed as an excipient able to delay the release of drugs with absorption at lower intestine or colon. This ampholytic excipient is seems self-stabilized not only by hydrogen associations, but also by ionic interactions and appears adequate 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). Polyvinyl alcohol (PVA) polymer have been proven as acceptable biomaterial 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, another natural carbohydrate, 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 chitosan modified as CarboxyEthyl(CE)-Chitosan in association to PVA will generate biomaterials of interest for implants and vascular grafts and for devices for hepatocyte and neurons in culture.