A. L. Iordanskii

Structure and prolonged transport in a biodegradable poly(R-3-hydroxybutyrate)-drug system

In order to create new biodegradable systems for the targeted transport of drugs, poly(3-hydroxy-butyrate) films containing the antibiotic rifampicin in an amount of 5–15 wt % as a model drug are prepared. Film surfaces are studied via scanning electron microscopy, and various structural elements (globules and fibrils) are found. Polymer samples isolated from melt or solution feature different degrees of porosity. It is shown that the kinetic profiles of rifampicin release are of an abnormal character. An analysis of the profiles shows that the release of rifampicin is controlled by the superposition of two processes: its desorption via the diffusion mechanism (the nonlinear segment) and hydrolytic degradation of poly(3-hydroxybutyrate) (the extended linear segment), which becomes well defined after completion of the diffusion stage. The diffusionkinetic model of the process is developed.

Structural-dynamic characteristics of matrices based on ultrathin poly(3-hydroxybutyrate) fibers prepared via electrospinning

Structural-dynamic analysis based on combined thermophysical and molecular mobility measurements via spin-probe ESR spectroscopy has been applied to films and fibrous matrixes based on poly(3-hydroxybutyrate). The dynamic behaviors of partially crystalline samples during deformation under conditions of electrospinning and cold rolling have been compared. The comparative results of the complex investigation of films and ultrathin fibers in the poly(3-hydroxybutyrate) matrix have shown that the electromechanical action leads to additional crystallization of the crystalline regions, spherulites, and lamellas in the polymer. The changes in the crystalline phase of the polymer are accompanied by an increase in the packing density of macromolecules in the intercrystalline space. With the use of the spin-probe ESR method, the effect of water and the oxidant ozone on the morphology of the amorphous phase of poly(3-hydroxybutyrate) ultrathin fibers has been determined. The measurements of the dynamics of spin-probe rotation in samples before and after cold rolling have shown that the additional orientation of poly(3-hydroxybutyrate) spherulites in a mechanical field results in stabilization of amorphous regions more resistant to the aggressive effects of ozone.

Probe mobility dynamics, crystal structure, and isotope exchange in PHBV and SPEU blend compositions

176 Biodegradable compositions based on natural polymers in combination with synthetic polymers offer an alternative to individual polymers. Blending is expectable to endow the composition with some new physicochemical characteristics that are not intrinsic to its individual components. Innovation technologies employ biodegradable systems for the targeted trans port of drugs and for the manufacture of environmentally friendly construction materials and packaging [1, 2]. Due to the unique combination of thromboresistance and mechanical characteristics, segmented polyether urethanes (SPEUs) are widely used in diverse fields of engineering and biomedicine as construction and functional materials. However, dimethyl isocyanate– based SPEUs are well known to have low biodegrada tion rates. This is a positive factor where long opera tion times are required, but may be considered as a limitation for short times of use. The lifetime of a sys tem can be tailored by blending SPEUs with other biopolymers, such as polyhydroxyalkanoates [3]. Poly(3 hydroxybutyrate) (PHB), a representative poly hydroxyalkanoate, combines useful properties with some undesired properties, namely, high costs and fra gility. These limitations are eliminated by PHB copol ymers with 3 hydroxyvalerate (PHBV) and composi tions with other biomedical polymers, in particular, with chitosan [4]. Varying the component ratio of the PHBV–SPEU composition and thereby influencing the morphology and crystallinity, one can manufac ture composition materials with diversified physico chemical characteristics, such as permeability, water solubility, destruction mechanism and destruction rates, and others. An efficient way to evaluate the states of amor phous and crystalline phases in polymers and polymer blends is a combination of dynamic and structural techniques. In this study, the dynamic techniques used are electron probe microanalysis, ESR, and deuterium isotope exchange. The structural techniques used are wide angle X ray diffraction and differential scanning calorimetry (DSC). Such a combination of structural and dynamic characteristics allows a more complete ascertainment of the structural evolution of PHBV– SPEU blends in an aqueous medium, preceding the hydrolytic decomposition of the polymer system, in the range of small times (hours). The subject matter of this study was blend compo sitions based on a PHBV biodegradable natural copoly mer (from Tianan) and SPEU (from BASF Elastog ran). The characteristics of the individual components were as follows: for SPEU: Mw = 2.29 × 10 5, Mn = 5.3 × 104, and ρ = 0.97 g/cm3; and for PHBV: Mw = 2.4 × 10 5, Mn = 1.5 × 10 5, and ρ = 1.25 g/cm3. The component ratio in PHBV–SPEU blends was varied in the follow ing sequence (wt/wt): 60 : 40, 50 : 50, and 40 : 60. Polymer films were prepared by evaporating a solvent (chloroform or tetrahydrofuran) from polymer solu tions on glass surfaces. Molecular mobility was studied by a spin probe method with determination of the correlation time τ, which characterizes the rotation mobility of the TEMPO probe, using a conventional ESR procedure [5]. DSC studies were carried out on a Netzsch DSC 204 F1 analyzer in an inert (argon) atmosphere with a heating rate of 10 K/min. X ray dif fraction was measured from film samples in transmis sion geometry on a Bruker Advance D8 diffractometer (CuK α radiation). The IR spectra of deuterated films were recorded on a Bruker IFS 48 FTIR spectropho tometer with a resolution of 2 cm–1 using 256 scans for each spectrum. X ray diffraction measurements showed high crys tallinities of PHBV and PHB samples [4]. The X ray diffraction patterns of PHBV films show at least five reflections corresponding to an orthorghombic lattice PHYSICAL CHEMISTRY

Development of a biodegradable polyhydroxybutyrate-chitosan-rifampicin composition for controlled transport of biologically active compounds

60 The development of therapeutic systems for pro longed and targeted transport of biologically active compounds is a topical task but a challenge for practi cal implementation. Extensive studies of polymeric dosage forms [1] provided two basic conclusions: first, at the micro and nanolevels, most beneficial are the biodegradable polymeric systems whose molecules are destroyed to give nontoxic intermediate or final prod ucts [2]; second, the search for polymer carriers requires the use of blend compositions provided that their physicochemical and transport characteristics are superior to these characteristics of the initial poly mers [3].

Changes in the structural parameters and molecular dynamics of polyhydroxybutyrate-chitosan mixed compositions under external influences

Differential scanning calorimetry (DSC), EPR probe analysis, large-angle X-ray diffraction (XRD), and UV spectroscopy are used to study the molecular dynamics and structure of hydroxybutyrate (PHB) copolymer, chitosan, and mixed compositions thereof upon thermal treatment in an aquatic medium. It is shown that, in mixed compositions, starting from 30% PHB, the correlation time increases by an order of magnitude, indicative of a sharp slowdown of the molecular mobility of the probe, and, concurrently, the degree of crystallinity decreases abruptly, as evidenced by DSC and XRD analyses. The diffusion coefficient of rifampicin in mixed compositions also decreases with increasing PHB content. A short-term (1 h) thermal treatment (at 70°C) in water results in an increase in the molecular mobility of the probe in the system. Crystallinity changes in complex ways.

Magnetic and transport properties of magneto-anisotropic nanocomposites for controlled drug delivery

Biodegradable polymeric film composites consisting of chitosan (Cht) and poly(3-hydroxybutyrate) (PHB) have been produced and used to encapsulate colloidal magnetite nanoparticles (MNPs) and a drug (dipyridamole). The magnetic organization of the MNPs induced by the exposure of the films to external magnetic fields was analyzed using ferromagnetic resonance and electron microscopy. A calculation of the relative abundance of aggregated nanoparticles showed that more than 14% of the particles were aggregated at total particle concentrations ranging from 3 to 8 mass %. Modification of the PHB-Cht composite matrix by nanoparticles has been proven to evoke changes in drug release kinetics, since the particles formed ordered magneto-anisotropic structures when exposed to external magnetic fields. The highest rate of transfer by diffusion was observed in the case of a nonisotropic matrix in which the orientation of particle aggregates coincided with the direction of the diffusion flux; the rate of drug release was the lowest in anisotropic matrices of biodegradable magneto-anisotropic nanocomposites with particle orientation perpendicular to the direction of diffusion. The physical reasons for the dependence of the release kinetics on the magnetic anisotropy of the samples are discussed. The results of the present study are indicative of the possibility of creating a new generation of therapeutic systems for the targeted delivery and sustained release of drugs controlled by a magnetic field.

Influence of the film forming procedure on the interaction in polyhydroxybutyrate-polyurethane blends

The structural features of polymeric composites based on polyhydroxybutyrate and segmented polyurethane were studied. A study by the methods of H-D exchange and IR spectroscopy revealed no intermolecular interaction between polyhydroxybutyrate and polyurethane in the blends prepared using a single solvent. The interaction of the polymers is observed when using two solvents and performing high-temperature heat treatment.

Nonwoven blend composites based on poly(3-hydroxybutyrate)–chitosan ultrathin fibers prepared via electrospinning

With the use of scanning electron microscopy, differential scanning calorimetry, and electron paramagnetic resonance, the structural–dynamic analysis of ultrathin fibrous matrixes based on poly(3-hydroxybutyrate) and blend composites of this polymer with chitosan is performed. It is shown that the addition of a small amount of chitosan causes change in the morphologies of the matrixes and leads to a marked increase in their melting enthalpies. It is found that the studied fibers contain amorphous regions with various morphologies. The dynamics of the spin probe TEMPO in these regions is investigated, and its change under the influence of increased temperature, an aqueous medium, and ozone is examined. The mechanism controlling the effects of chitosan, temperature, and an oxidative aggressive medium on the structuring of fibers is advanced.

Structure-Formation Features in Ultrathin Fibers of Poly(3-Hydroxybutyrate) Modified with Nanoparticles

Supramolecular structure formation of poly(3-hydroxybutyrate) ultrathin fibers prepared by electrospinning and the influence of low concentrations of silicon and TiO2 nanoparticles on the structure, physicomechanical and sorption properties, and resistance to thermal destruction and thermoand photo-oxidative destruction of non-woven fibrous material based on these fibers were studied. It was found that nanoparticles promoted the formation of thinner fibers with enhanced physicomechanical parameters and a structure that was more resistant to thermal and thermo- and photo-oxidative destruction and had a positive effect on the growth dynamics of mesenchymal stem cells.

Effect of Rolling on the Structure of Fibrous Materials Based on Poly(3-Hydroxybutyrate) and Obtained by Electrospinning

In this paper, we study the effect of rolling on the structure of fibrous materials based on poly(3-hydroxybutyrate) (PHB) and obtained by electrospinning. We have used electron paramagnetic resonance to demonstrate the effect of water and an oxidant (ozone) on the amorphous phase of the PHB matrix, formed by ultrathin fibers. We have established that additional orientation of PHB spherulites in a mechanical field leads to stabilization of the amorphous regions, which are more resistant to exposure to an aggressive ozone atmosphere. Studying the DSC curves for melting of the fibrous materials has shown that mechanical rolling leads to a bimodal distribution of the crystalline phase into more perfect and less perfect crystalline regions. The series of studies of ultrathin fibers proposed made it possible to analyze the changes in the segmental mobility of the polymer molecules in the early stages of their interaction with aqueous and oxidizing aggressive environments.