Preparation And Characterization Of PHBV-g-PVP Copolymers And Their Applications In Sustained Release Materials

Poly(3-hydrobutyrate-co-3-hydroxyvalerate) (PHBV), is one type of thermoplastic aliphatic polyester synthesized by bacterial intracellular under unbalanced growing conditions. PHBV has many good properties such as biodegradability, biocompatibility, piezoelectricity, optics activity and so on. With the shortage of energy and the increasing concern for environmental protection all over the world, the exploration and application of PHBV is attracting more and more interests in research and industry fields. The raw polymer of PHBV has been produced on industrialized scale. However, the process of PHBV products is difficult and the mechanical property of finished products is rigid and brittle, as a result, the applications of PHBV are very limited nowadays. In present study, the polar functional groups of poly(N-vinylpyrrolidone) (PVP) were introduced into the PHBV backbone by graft modification and the copolymers of PHBV grafted with PVP (PHBV-g-PVP) were synthesized. Because both substrate PHBV and side PVP chains have good biocompatibility, the graft copolymers are expected to be applied in biomaterials above all. In additional, PHBV-g-PVP could be further functionalized because PVP groups have the remarkable complexion ability with many compounds.Firstly, Benzoyl peroxide (BPO) was used to initiate instantaneously the polymerization of N-vinylpyrrolidone (NVP) and the graft copolymerization of NVP onto PHBV backbone in chlorobenzene. PHBV-g-PVP samples were also prepared. In order to obtain the highest graft ratio (Graft%), the orthogonal array design method was adopted to optimize the reaction conditions. The optimized copolymerization conditions were the weight of NVP 10 g, weight of BPO 0.6 g, reaction temperature at 120℃and reaction time of 1 h. The highest grafting ratio of 10.48% could be obtained at these optimized copolymerization conditions. Based on the optimized reaction conditions, effects of NVP concentration, BPO concentration, reaction temperature and reaction time on the percentage of conversion (PC%), graft ratio (Graft%) and graft efficiency (GE%) were further discussed. Fourier transforming infrared (FTIR) and hydrogen nuclear magnetic resonance (¹H-NMR) spectra characterization of samples showed that the PVP groups were presented in PHBV-g-PVP. The existence of chemical bond between PHBV backbone and PVP groups in grafted samples was concluded by the comparative analysis of weight reduction and ¹H-NMR spectral characterization of PHBV-g-PVP samples and PHBV/PVP blends after selective extraction.Secondly, the effects of graft modification with PVP on the thermal stability, crystallization behavior, mechanical and biodegradable properties of PHBV were investigated. Thermo-gravimetric (TGA) analysis indicated that the mechanism of thermal degradation for all samples was similar. However, the dynamic thermal stability of PHBV-g-PVP samples increased remarkably with increasing the Graft%. The results of differential scanning calorimetry (DSC) measurements showed that the melting and nonisothermal crystallization behavior of PHBV-g-PVP was very different in comparison with raw PHBV depending on Graft%. The crystallization capability from melting decreased with increasing the Graft% of samples, however the melting temperature (T_m) of all samples was almost constant, and the two characteristic melting endothermal peaks of raw PHBV disappeared on the heating scans of all PHBV-g-PVP samples, indicating the disappearance of co-crystallization phenomena after graft modification. It is of interest to note that a new crystallization peak (T_ch) appeared at almost the same temperature in heating scans of all PHBV-g-PVP samples. Although the crystallization capability from melting decreased after graft modification, the apparent enthalpy of fusion (ΔH_m) of all samples was almost constant due to the occurrence of recrystallization on heating. The spherulitic morphology of samples was observed with a polarized optical microscopy (POM) equipped with a hot stage. All the spherulites crystallized at the given crystallization temperature (T_c) exhibited a typical black cross pattern formed by many concentric circles with different light and shade. The band space between concentric circles decreased with the decrease of T_c and the increase of Graft%. The spherulitic radial growth rates (SG) of samples isothermally crystallized at different temperature (T_c) were determined by observation with a POM. The results showed that the SG values of all samples reached a maximum at a certain crystallization temperature (T_max), while the T_max of grafted PHBV shifted to lower temperatures as the Graft% increased. At the same given T_c, the SG values of PHBV-g-PVP samples decreased with increasing Graft% of samples. Analysis on the isothermal crystallization kinetics according to Lauritzen-Hoffman theory showed that the values of surface free energy (σ_e), nucleation constant (K_g) and the work of chain-folding per molecular fold (q) increased with increasing Graft% of samples. The increased values of K_g andσ_e indicated that the nucleus formation and spherulitic growth became more difficult after graft modification. These results were in agreement with the analysis by DSC scans. The increased q value indicated the higher rigidity of chains after graft modification. The results of mechanical measurements on PHBV and PHBV-g-PVP fluid films showed that all samples were brittle. Young's modulus increased while the elongation of grafted PHBV films decreased with increasing Graft% of samples, indicating that the higher brittleness of samples after graft modification. This conclusion was in agreement with the analysis of isothermal crystallization kinetics. PHBV and PHBV-g-PVP films were biodegradable in soil suspension. The mass of films decreased while the molecular weight was almost constant with increasing the biodegradable period. By scanning electric microscope (SEM), smaller pits were observed on the surface of all films at the beginning of degradation, and the pits increased in size as the degradation proceeded, while surface degradation was not even at all the time. All the results indicated that the degradation of PHBV and PHBV-g-PVP membranes in soil suspension was the corrosion course of film surface, namely enzymatic degradation.Lastly, Tetracycline Hydrochloride (TC) as a model drug was loaded in fluid films and electrospun sheets using PHBV and PHBV-g-PVP with different Graft% as drug deliver substrates. The vitro release of TC from drug carriers in pH buffer solution (PBS) was investigated. The surface hydrophilicity of sustained drug release films was investigated and the results showed that the PBS contact angle on PHBV-g-PVP films decreased, implying hydrophilicity was improved with increasing Graft% of substrates. In comparison with the drug loaded films, the drug loaded electrospun sheets exhibited high hydrophobic property being independent of Graft%. However, the drug loaded electrospun sheets exhibiting hydrophobic surface had remarkably higher water retention capability than drug loaded films due to the high porosity structure of electrospun sheets. The electrospun mat could absorb the amount of water equal to 160%-220% of its self-weight in saturation. The release of TC from drug loaded films and electrospun sheets in PBS was studied and it was found that all samples gave remarkably slow release in comparison with pure TC, namely all drug loaded films and electrospun sheets had good sustained release effects. All drug loaded films led to a sharp initial burst, but electrospun sheets gave almost steady release of drug at all time. The morphology of fibers was smooth and did not exhibit the enrichment of TC particles in electrospun sheets before release experiment as revealed by SEM. The morphology of fibers did not change obviously after release experiment. With increasing the Graft% of substrate, drug loaded films and electrospun sheets gave the higher drug release rate.