Estelle Renard

Poly(3-hydroxyoctanoate) containing pendant carboxylic groups for the preparation of nanoparticles aimed at drug transport and release

Copolymers of poly(3-hydroxyoctanoate) (PHO) with carboxylic groups in lateral chains have been prepared by chemical modification of unsaturated bacterial polyesters. The oxidation of the pendant alkenes is complete and important loss in molecular weight of polymer was observed. The presence of repeating units containing pendant carboxy groups in the proportion of 25% has enhanced hydrophilicity of these new polymeric structures. Nanoparticles have been prepared from PHO and two functionalized derivatives, characterized by electronic microscopy and compared in view of bioactive molecules transport and release.

Preparation of a novel artificial bacterial polyester modified with pendant hydroxyl groups.

The Poly(hydroxyalkanoate) (PHA) chemical modifications represent an alternative route to introduce functional groups, which cannot be introduced by bioconversion. PHAs containing unsaturated chains were readily converted into polyesters containing a terminal hydroxyl group on the side chains. With the use of the borane-tetrahydrofuran complex, the pendant side chain alkenes were quantitatively transformed into hydroxyl functions. The conversion proceeded to completion without a significant decrease in molecular weight. The introduction of hydroxyl groups in the products was confirmed from Fourier transform infrared and 1H NMR analysis. The presence of repeating units containing pendant hydroxyl groups in the proportion 25 mol % caused an increase in hydrophilicity of these new PHAs because they were soluble in polar solvents such as ethanol. Besides, these reactive PHAs can be used to bind bio-active molecules or to prepare novel graft copolymers with desired properties.

Chemical modifications of bacterial polyesters: from stability to controlled degradation of resulting polymers

Abstract Polyhydroxyalkanoates (PHAs) form an enlarged family of biopolyesters, which are biocompatible, biodegradable and non-toxic. Polyhydroxyalkanoates biodegradation corresponds to a hydrolysis involving endo- or exo-enzymatic systems in the breaking cleavage of esters bonds. This type of degradation is needed for environmental applications. In the case of therapeutic and biomedical uses, a simple hydrolysis is required. Hydrolytic degradation of PHAs is not evident as shown on poly(3-hydroxyoctanoate) (PHO) and is depending on the structure of the polyester and more particularly on the nature of the side chains. In some cases, blending with others polymers has decreased PHAs crystallinity and has made easier hydrolysis. Another route consists in the preparation of unsaturated PHAs which can be chemically modified. Pendant double bonds have been turned into carboxylic, hydroxyl or epoxy groups. Moreover these reactive functions were used for grafting oligomers of hydrolysable polylactic acid (PLA) or hydrophilic polyethylene glycol (PEG). Otherwise block copolymers with polycaprolactone (PCL) have been prepared, aiming at nanoparticles formation in the view of drug release. Therefore, the hydrophilic/hydrophobic balance of these materials was controlled by chemical modification and their stability/hydrolysis has been studied. Results have shown that the most suitable products in regard to hydrolysis concern PHAs containing carboxylic groups in side chains, noted poly(3hydroxyoctanoate-co-9-carboxy-3-hydroxydecanoate) and its derivatives. Carboxylic groups promote water penetration into the polymer and participate to ester groups hydrolysis through better water penetration and catalysis.

Modification of the face selectivity in asymmetric induction by cyclodextrins through the formation of three-component inclusion compounds

Stoichiometric amounts of triethylamine (TEA) were found to enhance the chiral induction by β-cyclodextrin (β-CD) in the reduction of acetophenone (ACPH) by aqueous NaBH4. The enantioselectivity obtained depends upon the molar ratio β-CD:ACPH:TEA. Evidence for the formation of a three-component inclusion compound was obtained from detailled1H and2H NAM studies. The restriction of the molecular motion of the prochiral center probably accounts for the strong enhancement of the chiral induction observed.