Effect of Drug Encapsulation and Hydrothermal Exposure on the Structure and Molecular Dynamics of the Binary System Poly(3-hydroxybutyrate)-chitosan.

In this work, film materials based on binary compositions of poly-(3-hydroxybutyrate) (PHB) and chitosan with different ratios of polymer components in the range from 0/100 to 100/0 wt. % were studied. Using a combination of thermal (DSC) and relaxation (EPR) measurements, the influence of the encapsulation temperature of the drug substance (DS) of dipyridamole (DPD) and moderately hot water (at 70 °C) on the characteristics of the PHB crystal structure and the diffusion rotational mobility of the stable TEMPO radical in the amorphous regions of the PHB/chitosan compositions is shown. The low-temperature extended maximum on the DSC endotherms made it possible to obtain additional information about the state of the chitosan hydrogen bond network. This allowed us to determine the enthalpies of thermal destruction of these bonds. In addition, it is shown that when PHB and chitosan are mixed, significant changes are observed in the degree of crystallinity of PHB, degree of destruction of hydrogen bonds in chitosan, segmental mobility, sorption capacity of the radical, and the activation energy of rotational diffusion in the amorphous regions of the PHB/chitosan composition. The characteristic point of polymer compositions was found to correspond to the ratio of the components of the mixture 50/50%, for which the inversion transition of PHB from dispersed material to dispersion medium is assumed. Encapsulation of DPD in the composition leads to higher crystallinity and to a decrease in the enthalpy of hydrogen bond breaking, and it also slows down segmental mobility. Exposure to an aqueous medium at 70 °C is also accompanied by sharp changes in the concentration of hydrogen bonds in chitosan, the degree of PHB crystallinity, and molecular dynamics. The conducted research made it possible for the first time to conduct a comprehensive analysis of the mechanism of action of a number of aggressive external factors (such as temperature, water, and the introduced additive in the form of a drug) on the structural and dynamic characteristics of the PHB/chitosan film material at the molecular level. These film materials have the potential to serve as a therapeutic system for controlled drug delivery.

Structure and Properties of Biopolymeric Fibrous Materials Based on Polyhydroxybutyrate-Metalloporphyrin Complexes.

Ultrathin fibrous materials based on natural bacterial polymer polyhydroxybutyrate (PHB) were prepared by the electrospinning method. Using scanning electron and optical microscopy techniques the macrophysical characteristics of the fibrous layer were determined and classified. The physicomechanical characteristics of the resultant materials and their changes caused by ozonation were determined as well. Structure formation in the ultrathin polyhydroxybutyrate fibers containing low antibacterial concentrations was studied. The effect of low concentrations of zinc tetraphenylporphyrin and iron(III) chloroteteraphenylporphyrin complexes on the structure of polyhydroxybutyrate-based ultrathin fibers was elucidated. Techniques used in the study were X-ray diffraction analysis, ESR spin probe method, differential scanning calorimetry, and optical and electron scanning microscopy. It was shown that addition of the metal porphyrin complexes caused changes in the degree of crystallinity and in the crystallite size of the PHB fibers, while the proportion of dense domains in the amorphous phase of the polymer fiber increased.

PLLA-PHB fiber membranes obtained by solvent-free electrospinning for short-time drug delivery.

Fibers of poly(L-lactic acid) (PLLA)/polyhydroxybutyrate (PHB) with different concentrations of the drug dipyridamole (DPD) were prepared using solvent-free melt electrospinning to obtain a polymeric drug delivery system. The electrospun fibers were morphologically, structurally, thermally, and dynamically characterized. Crazes that resemble lotus root crevices were interestingly observed in the 7:3 PLLA/PHB fibers with 1% DPD. The crystallinity of PLLA slightly decreased as PHB was incorporated, and the addition of DPD significantly reduced the melting temperature of the composite. The interactions between PLLA and PHB mainly occurred at a proportion of 7:3, and drug encapsulation in the fibers was verified. The kinetic profiles of drug release demonstrated the predominant multiple patterns involving a diffusional stage in the short-term mode of release and kinetic process related to the hydrolysis of the biopolymers. Furthermore, the dynamic behavior of the polymer molecules was evaluated based on the segmental mobility using probe electron spin resonance spectroscopy. The segmental mobility in the amorphous fraction of PLLA decreased with increasing PLLA content. The 9:1 PLLA/PHB system was more resistant to polymer hydrolysis than to the 7:3 system and the rate of diffusion transport was approximately two times higher for the 7:3 PLLA/PHB fibers than for the 9:1 PLLA/PHB fibers.

[A comparative study of biodegradation kinetics of biopolymer systems based on poly(3-hydroxybutyrate)].

The aim of this study was to evaluate and to compare of long-term kinetics curves of biodegradation of poly(3-hydroxybutyrate) (PHB), its copolymer poly(3-hydroxybutyrate-co-3-hydroxyvalerate), and PHB/polylactic acid blend. The total weight loss and the change of average viscosity molecular weight were used as an index of biodegradation degree. The rate of biodegradation was analyzed in vitro in presence oflipase and in vivo when the films were implanted in animal tissues. The morphology of PHB films surface was studied by atomic force microscopy technique. It was shown that biodegradation of PHB is occurred by means of as polymer hydrolysis, and as its enzymatic biodegradation. The obtained data can be used for development of medical devices on the base of PHB.

[New poly-(3-hydroxybutyrate)-based systems for controlled release of dipyridamole and indomethacin].

New poly-(3-hydroxybutyrate)-based systems for controlled release of anti-inflammatory and antithrombogenic drugs have been studied. The release occurs via two mechanisms (diffusion and degradation) operating simultaneously. Dipyridamole and indomethacin diffusion processes determine the rate of the release at the early stages of the contact of the system with the environment (the first 6-8 days). The coefficient of the release diffusion of a drug depends on its nature, the thickness of the poly-(3-hydroxybutyrate) films containing the drug, the concentrations of dipyridamole and indomethacin, and the molecular weight of the poly-(3-hydroxybutyrate). The results obtained are critical for developing systems of release of diverse drugs, thus, enabling the attainment of the requisite physiological effects on tissues and organs of humans.

Aerobic and anaerobic microbial degradation of poly-beta-hydroxybutyrate produced by Azotobacter chroococcum.

Food industry wastewater served as a carbon source for the synthesis of poly-beta-hydroxybutyrate (PHB) by Azotobacter chroococcum. The content of polymer in bacterial cells grown on the raw materials reached 75%. PHB films were degraded under aerobic, microaerobic, and anaerobic conditions in the presence and absence of nitrate by microbial populations of soil, sludges from anaerobic and nitrifying/denitrifying reactors, and sediment from a sludge deposit site. Changes in molecular mass, crystallinity, and mechanical properties of PHB were studied. Anaerobic degradation was accompanied by acetate formation, which was the main intermediate utilized by denitrifying bacteria or methanogenic archaea. On a decrease in temperature from 20 to 5 degrees C in the presence of nitrate, the rate of PHB degradation was 7.3 times lower. Under anaerobic conditions and in the absence of nitrate, no PHB degradation was observed, even at 11 degrees C. The enrichment cultures of denitrifying bacteria obtained from soil and anaerobic sludge degraded PHB films for a short time (3-7 d). The dominant species in the enrichment culture from soil were Pseudomonas fluorescens and Pseudomonas stutzeri. The rate of PHB degradation by the enrichment cultures depended on the polymer molecular weight, which reduced with time during biodegradation.

Modeling of the drug delivery from a hydrophilic transdermal therapeutic system across polymer membrane.

A mathematical simulation is presented which describes the in vitro drug delivery kinetics from hydrophilic adhesive water-soluble poly-N-vinylpyrrolidone (PVP)-polyethylene glycol (PEG) matrices of transdermal therapeutic systems (TTS) across skin-imitating hydrophobic Carbosil membranes. Propranolol is employed as the test drug. The contributions of the following physicochemical determinants to drug delivery rate control have been estimated: the drug diffusion coefficients both in the matrix and the membrane; the membrane-matrix drug partition coefficient: the drug concentration in the matrix and the membrane thickness. Drug transfer from the hydrophilic matrix across the membrane is shown to be controlled by the drug partitioning from the matrix into the membrane. The best correlation between simulation data and experimental results is obtained when the effect of membrane hydration is taken into consideration during in vitro drug release.

Modeling of percutaneous drug transport in vitro using skin-imitating Carbosil membrane.

A comparative study of the barrier function of human skin and polydimethylsiloxane-polycarbonate block copolymer Carbosil membrane was performed in vitro using 14 drugs spanning a wide range of structures and therapeutic classes. The drug permeability coefficients across the skin and the Carbosil membrane wee examined as an explicit dependence of permeant molecular weight, melting point, solubility in aqueous solution in aqueous solution and octanol-water partition coefficient. Owing to heterophase and heteropolar structure, Carbosil membranes and human skin epidermis share a common solubility-diffusion mechanism of drug transport. This synthetic membrane is shown to provide a mechanistically substantiated model for percutaneous drug absorption. Carbosil membrane can be used both foe quantitative prediction for transdermal drug delivery rate and as a skin-imitating standard membrane in the course of in vitro drug delivery kinetics evaluation.

The importance of the diffusive transfer of tints in the technology of tinting of soft contact lenses.

This paper deals with the kinetics of tint transfer in soft contact lenses. A mathematical model taking into account both diffusion and chemical reactions is proposed and physicochemical parameters are determined. It is shown that bulk tinting is more effective in practice than surface tinting.

[Adsorption of plasma proteins on the surface of hydrophobic polymers. Structural aspects]. / Adsorbtsiia plazmennykh belkov na poverkhnosti gidrofobnykh polimerov. Strukturnyi aspekt.

The qualitative and quantitative composition of the adsorbed protein layer is determined by thromboresistance of artificial polymer surface. The adsorption of albumine and gammaglobuline from buffer solution to the hydrofobic polymer surfaces was investigated with ESR and electron spectroscopic method. The existence of two kinds of protein covering was demonstrated: reversible and irreversible protein layer. During the nitroxyl labelled globuline adsorption the spectrum of label is due to superposition of both reversible and irreversible kinds of adsorption. It was demonstrated by the electron microscopic method that the strongly adsorbed protein layer corresponds with the denaturated protein, the reversibly adsorbed protein in contrast is native. The architecture of protein layer on polymer surface was also investigated. The comparison of structural and physiological properties of serum protein is important for the investigation of the thromboresistant materials.