Scientific publications - Biopolymer


Pravata, L., Braud, C., Boustta, M., El Ghzaoui, A., Tømmeraas, K., Guillaumie, F., Schwach-Abdellaoui, K., Vert, M.

"New amphiphilic lactic acid oligomer - Hyaluronan conjugates: Synthesis and physicochemical characterization"

Biomacromolecules, 9 (1), pp. 340-348. (2008)

The "grafting onto" strategy was used to conjugate DL-lactic acid oligomers (OLA) to hyaluronan (HA) for the sake of developing novel degradable HA-based self-assembling polymeric systems. Grafting was achieved by reacting COCI-terminated OLA with cetyltrimethylammonium hyaluronate (CTA-HA) in dimethyl sulfoxide (DMSO). The resulting CTA-HAOLA conjugates were purified and turned to sodium form (Na-HAOLA) by dissolution in a phosphate buffer-DMSO mixture and successive dialyses against DMSO, ethanol, and water. In contrast, when the same protocol was applied to CTA-HAOLA, phase separation with get formation was observed. The solution phase was composed of Na-HAOLA whereas the gel phase was made of mixed CTA-Na-HAOLA salt with ca. 25% of the carboxyl groups neutralized by CTA. Gelation was assigned to intramolecular hydrophobic associations between OLA and cetyl alkyl chains that complemented electrostatic interactions between CTA and HA COO- groups synergistically. Therefore, the corresponding stabilized CTA ions required more drastic conditions to be released. Under the selected dialysis conditions, the CTA-Na-HAOLA gels formed tiny tubes. Na-HAOLA and CTA-Na-HAOLA were characterized by FTIR, one-dimensional 1H and two-dimensional 1H NMR. The extent of grafting was ca. 5% per disaccharidic repeating unit, regardless of the molecular weight, as determined by NMR and capillary zone electrophoresis. Amphiphilic Na-HAOLA molecules were aggregated and formed spherical species in water according to size exclusion chromatography combined with multiangle laser light scattering detection. The critical aggregation concentration ranged between 0.2 and 0.35% (w/v), depending of the molecular weight of the parent hyaluronan. © 2008 American Chemical Society.

Fojan, P., Schwach-Abdellaoui, K., Tømmeraas, K., Gurevich, L., Petersen, S.B.

"Polysaccharide based nanoparticles and nanoporous matrices"

2006 NSTI Nanotechnology Conference and Trade Show - NSTI Nanotech 2006 Technical Proceedings, 2, pp. 79-82. (2006)

In this paper we present an Atomic Force Microscopy (AFM) study of a biopolymer which is capable of forming different phases. We observed a wide range of phases varying from condensed polymer strands, forming networks on a support, to nano particles of different size distributions to porous matrices with a flat surface. The formation of these different phases is depending on the concentration of the biopolymer. At high concentrations it is self organizing into a regular gel like matrix, whereas at lower concentrations nano particles are being the dominant structures together with a network of condensed self organized strands, covering the support. Due to its unusual properties and its high water retention this material has a broad application potential both in pharmaceutical and cosmetic industry as well as in the field of tissue engineering.

Sharma, A.K., Kumar, R., Canteenwala, T.C., Parmar, V.S., Patkar, S., Kumar, J., Watterson, A.C.

"Biocatalytic synthesis and characterization of copolymers based on poly(ethylene glycol) and unsaturated methyl esters"

Journal of Macromolecular Science - Pure and Applied Chemistry, 42 A (11), pp. 1515-1521. (2005)

Biocatalytic organic synthesis has proved to be a significant breakthrough in the area of polymer synthesis. Environmentally benign methodology and the use of mild reaction conditions are a hallmark of this approach. We have studied the biocatalytic synthesis of unsaturated polyesters under solventless conditions by the condensation copolymerization of dimethyl fumarate and dimethyl maleate with polyethylene glycol (PEG) catalyzed by Novozyme435 (immobilized Candida antarctica lipase B). The structures of the resulting polymers, poly(ethylene glycol)codimethyl fumarate and poly(ethylene glycol)codimethyl maleate were studied from their 1 H and 13 CNMR spectra. The molecular weights of polymers were determined by size exclusion chromatography. Copyright © Taylor & Francis, Inc.

Widner, B., Behr, R., Von Dollen, S., Tang, M., Heu, T., Sloma, A., Sternberg, D., Deangelis, P.L., Weigel, P.H., Brown, S.

"Hyaluronic acid production in Bacillus subtilis"

Applied and Environmental Microbiology, 71 (7), pp. 3747-3752. (2005)

The hasA gene from Streptococcus equisimilis, which encodes the enzyme hyaluronan synthase, has been expressed in Bacillus subtilis, resulting in the production of hyaluronic acid (HA) in the 1-MDa range. Artificial operons were assembled and tested, all of which contain the hasA gene along with one or more genes encoding enzymes involved in the synthesis of the UDP-precursor sugars that are required for HA synthesis. It was determined that the production of UDP-glucuronic acid is limiting in B. subtilis and that overexpressing the hasA gene along with the endogenous tuaD gene is sufficient for high-level production of HA. In addition, the B. subtilis-derived material was shown to be secreted and of high quality, comparable to commercially available sources of HA. Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Widner, W., Behr, R., Tang, M., Hue, T., Sternberg, D., Von Dollen, S., Sloma, A., Weigel, P.H., Brown, S.H.

"Metabolic engineering of Bacillus subtilis for biosynthesis of hyaluronic acid - A superior system for industrial HA production"

Transactions - 7th World Biomaterials Congress, p. 40. (2004)

Biosynthesis of Hyaluronic acid (HA) by Bacillus Subtilis was discussed. It was found that the presence of tuaD in the expression cassette was required for HA production above trace levels. Overall, yields of HA from the recombinant B. subtilis strains were in the multi-gram per liter range, comparable to reported Streptocioccal yields. GPC-MALLS analysis of fermentation samples indicated a molecular weight in the 1-2 MDa range with a polydispersity index below 1.5.