E. A. Ivanov

Hydrolytic Degradation of Poly(3-hydroxybutyrate), Polylactide and their Derivatives: Kinetics, Crystallinity, and Surface Morphology

Hydrolytic degradations of biodegradable poly(3-hydroxybutyrate) (PHB), polylactide (PLA) and their derivatives were explored by kinetic and structure methods at 37 and 70°C in phosphate buffer. It was revealed the kinetic profiles for copolymer PHBV (20% of 3-hydroxyvalerate) and the blend PHB-PLA (1:1 wt. ratio). The intensity of biopolymer hydrolysis depending on temperature is characterized by total weight loss and the viscosity-averaged molecular weight decrement (ΔMW) as well as by WAXS and AMF techniques. Characterization of PHB and PHBV includes both ΔMW and crystallinity evolution (x-ray diffraction) as well as the AFM analysis of PHB film surfaces before and after aggressive medium exposition. The degradation is enhanced in the series PHBV < PHB < PHB-PLA blend < PLA. The impact of MW on the biopolymer hydrolysis is shown.

Biodegradation kinetics of poly(3-hydroxybutyrate)-based biopolymer systems

The aim of this study was to evaluate and to compare the long-term kinetics curves of biodegradation of poly(3-hydroxybutyrate) (PHB), its copolymer poly(3-hydroxybutyrate-co-3-hydroxyvalerate), and a PHB/polylactic acid composite. The total weight loss and the change of average viscosity molecular weight were used as the parameters reflecting the biodegradation degree. The rate of biodegradation was analyzed in vitro in the presence of lipase and in vivo after film implantation in animal tissues. The morphology of the PHB film surface was studied by the atomic force microscopy technique. It was shown that PHB biodegradation involves both polymer hydrolysis and its enzymatic biodegradation. The results obtained in this study can be used for the development of various PHB-based medical devices.

Biosynthesis of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) copolymer by Azotobacter chroococcum strain 7B

The ability of Azotobacter chroococcum strain 7B, producer of poly(3-hydroxybutyrate) (PHB), to synthesize its copolymer poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (P(3HB-co-3HV)) was studied. It was demonstrated, for the first time, that A. chroococcum strain 7B was able to synthesize P(3HB-co-3HV) with various molar rates of HV in the polymer chain when cultivated on medium with sucrose and carboxylic acids as precursors of HV elements in the PHB chain, namely, valeric (13.1–21.6 mol %), propanoic (3.1 mol %), and hexanoic (2.1 mol %) acids. Qualitative and functional differences between PHB and P(3HB-co-3HV) were demonstrated by example of the release kinetic of methyl red from films made of synthesized polymers. Maximal HV incorporation into the polymer chain (28.8mol %) was recorded when the nutrient medium was supplemented with 0.1% peptone on the background of 20 mM valerate. These results suggest that that the studied strain can be regarded as a potential producer of not only PHB but also P(3HB-co-3HV).

Microspheres based on poly(3-hydroxy)butyrate for prolonged drug release

The kinetics of the controlled release of the antiproliferative drug dipyridamole from microspheres based on the biocompatible and biodegradable polymer poly(3-hydroxy)butyrate is studied. As carriers for dipyridamole, microspheres prepared from a solution of poly(3-hydroxy)butyrate by single emulsion method are used. Under in vitro conditions, the kinetic curves describing the release of dipyridamole from microspheres with diameters of 19, 63, and 92 μm show two characteristic regions: the region of fast drug release within a short time period and a well-pronounced continuous linear region. For microspheres with a diameter of 4 μm, the linear region is missing. Analysis of the kinetic curves illustrating controlled drug release together with the measurements on polymer degradation shows that their kinetic profiles depend on the diffusion-controlled process and hydrolytic degradation of poly(3-hydroxy)butyrate. The diffusion kinetic equation describing both linear and nonlinear regions of dipyridamole released from the microspheres involves the sum of two terms: desorption from the sphere via the diffusion-controlled mechanism and drug release via the zero-order reaction. The linear region of the drug release curve is explained by the zero-order hydrolysis of poly(3-hydroxy)butyrate. The diffusion coefficients and kinetic constants are calculated. For bigger microspheres, the existence of the continuous linear region in the corresponding kinetic curves makes it possible to use microsystems based on poly(3-hydroxy)butyrate and dipyridamole as novel systems for local prolonged drug delivery.