Preparation and thermosensitivity of naturally occurring polypeptide poly(gamma-glutamic acid) derivatives modified by propyl groups

Poly(gamma-glutamic acid) (gamma-PGA) is a biosynthetic polymer, and the carboxyl groups are able to undergo a chemical modification. In this study, poly(alpha-propyl gamma-glutamate) (gamma-PGA propylate) was synthesized by the esterification of these carboxyl groups to yield a thermosensitive and biodegradable polymer. In aqueous solution, the gamma-PGA propylate can impart thermosensitivity by controlling the hydrophobic-hydrophilic balance of the gamma-PGA polymeric chains.     

Chelation of vanadium(IV) by a natural and edible biopolymer poly(gamma-glutamic acid) in aqueous solution: structure and binding constant of complex

The naturally occurring edible biopolymer poly(gamma-glutamic acid) (gamma-PGA) is shown to be an efficient chelating agent of vanadium(IV). The structure of poly(gamma-glutamic acid)oxovanadium(IV) (VO-gamma-PGA) complex in solution has been analyzed by electron spin resonance and UV-visible absorption spectra. The equatorial coordination sphere of vanadium(IV) is proposed to be [2 x carboxylate (2O)-VO-(OH2)2]. The binding isotherm is determined for suspensions of gamma-PGA in vanadium(IV) oxide sulfate (VS) solutions of different concentrations, and the data have been adjusted to fit the modified Langmuir equation. The maximum amount of vanadium bound per gram of gamma-PGA is estimated to be 141 mmol . g(-1) with a binding constant of 22 L . g(-1) at pH 3.     

Pyrogallic acid‐PLGA conjugate as new biodegradable material suitable for final sterilization by irradiation

This paper reports the feasibility to prepare a biodegradable material stable to γ‐irradiation by grafting of poly(lactide‐co‐glycolide) with pyrogallic acid (PLGA‐g‐PA) and ferulic acid (PLGA‐g‐FA) in mild condition. Only the grafting procedure with PA did not modify molecular weight (Mw) of the starting polymer and PLGA‐g‐PA showed antioxidant properties. The polymer degradation in pH 7.4 phosphate buffer saline (PBS) was mainly governed by a random chain scission mechanism according to a first‐order reaction. The irradiation at the dose of 25 kGy caused only a very slight decrease of Mw and the degradation patterns of the non‐irradiated and irradiated material were superimposable. PLGA‐g‐PA resulted a promising material to develop biodegradable drug delivery systems which would be sterilizable in the final container. Copyright © 2010 John Wiley & Sons, Ltd.     

Biodegradable polymer nanocomposites: An overview

Biodegradable polymer nanocomposites, due to their biodegradability and other improved properties possess tremendous scope in the industrial sector. This current article reviews the recent studies carried out over biodegradable polymer nanocomposites that includes preparation, characterization, properties, and applications of nanocomposites based on biodegradable polymers. An orderly introduction of nanocomposites prepared by using various biodegradable aliphatic polyesters and polymers obtained from biomass products has been brought about. A wide range of organic and inorganic nanoparticles was used as additives or fillers to prepare nanocomposites with improved desired properties. Considering vast research on layered silicates/polymer nanocomposites, a special emphasis has been summarized at the end of the review.     

Efficient production of poly-gamma-glutamic acid by Bacillus subtilis ZJU-7

A strain with high poly-gamma-glutamic acid (gamma-PGA) production was isolated from fermented bean curd, a traditional Chinese food. The strain was named Bacillus subtilis ZJU-7 according to 16s rDNA sequencing and its taxonomic characters. The culture conditions for gamma-PGA production were evaluated. The most suitable carbon and nitrogen sources were sucrose and tryptone, respectively. Exogenous L-glutamic acid was necessary for gamma-PGA production, and the production of gamma-PGA increased on the addition of L-glutamic acid to the medium. In the medium containing 60 g/L of sucrose, 60 g/L of tryptone, 80 g/L of L-glutamic acid, and 10 g/L of NaCl, the yield of gamma-PGA reached 54.4 g/L after cultivation at 37 degrees C for 24 h, which was the highest gamma-PGA production compared with values reported in the literature. The average molecular mass of gamma-PGA produced was about 1.24 x 106 Daltons. B. subtilis ZJU-7 is genetically stable and can synthesize levan instead of gamma-PGA without the addition of L-glutamic acid to the medium.     

Production and characterization of anisotropic particles from biodegradable materials

In recent years, production and characterization of anisotropic particles has become of interest in a wide range of scientific fields including polymer chemistry, drug delivery, electronics, energy, and nanotechnology. In this work, we demonstrate a novel formulation for production of anisotropic particles via an internal phase separation of biodegradable components. Specifically, binary mixtures of biodegradable polymers poly(lactic-co-glycolic acid), polycaprolactone, and biodegradable lipid Precirol (glyceryl palmitostearate) were dissolved in dichloromethane, emulsified, and prepared into anisotropic particles using a modified solvent evaporation technique. During the slow evaporation process the components self-assembled into anisotropic particles with distinct morphologies. Polymer/polymer formulations resulted in compartmentalized anisotropic heterodimer particles, while polymer/lipid combinations yielded "ice cream cone" shaped particles. It was found that addition of certain active pharmaceuticals resulted in an altered, pox-like segregation at the particle surface of polymer/polymer formulations. The anisotropic nature of the particles was subsequently characterized using optical microscopy, scanning electron microscopy, zeta potential, electrophoresis, and X-ray diffraction. Successful formulations presented here may potentially be employed as multicompartmental drug carriers with staggered drug release rates or alternatively as a colloidal excipient for an arsenal of pharmaceutical applications.     

Biodegradable polymer blends and composites: An overview

Biodegradable polymers belong to a family of polymer materials that found applications ranged from medical applications including tissue engineering, wound management, drugs delivery, and orthopedic devices, to packaging and films applications. For broadening their potential applications, biodegradable polymers are modified utilizing several methods such as blending and composites forming, which lead to new materials with unique properties including high performance, low cost, and good processability. This paper reviews the recent information about the morphology of blends consisting of both biodegradable and non-biodegradable polymers and associated mechanical, rheological, and thermal properties of these systems as well as their degradation behavior. In addition, the mechanical performance of composites based on biodegradable polymers is described.     

Encapsulation and sustained release of a model drug, indomethacin, using CO(2)-based microencapsulation

A carbon dioxide (CO(2))-based microencapsulation technique was used to impregnate indomethacin, a model drug, into biodegradable polymer nanoparticles. Compressed CO(2) was emulsified into aqueous suspensions of biodegradable particles. The CO(2) plasticizes the biodegradable polymers, increasing the drug diffusion rate in the particles so that drug loading is enhanced. Four types of biodegradable polymers were investigated, including poly(d,l-lactic acid) (PLA), poly(d,l-lactic acid-co-glycolic acid) (PLGA) with two different molar ratios of LA to GA, and a poly(d,l-lactic acid-b-ethylene glycol) (PLA-PEG) block copolymer. Biodegradable nanoparticles were prepared from polymer solutions through nonsolvent-induced precipitation in the presence of surfactants. Indomethacin was incorporated into biodegradable nanoparticles with no change of the particle size and morphology. The effects of a variety of experimental variables on the drug loadings were investigated. It was found that the drug loading was the highest for PLA homopolymer and decreased in PLGA copolymers as the fraction of glycolic acid increased. Indomethacin was predicted to have higher solubility in PLA than in PLGA based on the calculated solubility parameters. The drug loading in PLA increased markedly as the temperature for impregnation was increased from 35 to 45 degrees C. Drug release from the particles is a diffusion-controlled process, and sustained release can be maintained over 10 h. A simple Fickian diffusion model was used to estimate the diffusion coefficients of indomethacin in the biodegradable polymers. The diffusion coefficients are consistent with previous studies, suggesting that the polymer properties are unchanged by supercritical fluid processing. Supercritical CO(2) is nontoxic, easily separated from the polymers, can extract residual organic solvent, and can sterilize biodegradable polymers. The CO(2)-based microencapsulation technique is promising for the production of drug delivery devices without the use of harmful solvents.     

In vitro enzymatic degradation of nanoparticles prepared from hydrophobically-modified poly(gamma-glutamic acid)

Amphiphilic poly(gamma-glutamic acid) (gamma-PGA) was prepared by the introduction of L-phenylalanine ethylester (L-PAE) as a side chain. This gamma-PGA-graft-L-PAE formed monodispersed nanoparticles in water. The particle size of the gamma-PGA nanoparticles could be controlled by the degree of L-PAE grafting. The hydrolytic degradation and enzymatic degradation by gamma-glutamyl transpeptidase (gamma-GTP) of these gamma-PGA nanoparticles was studied by gel permeation chromatography (GPC) and scanning electron microscopy (SEM). The hydrolysis ratio of gamma-PGA was found to decrease upon increasing the hydrophilicity of the gamma-PGA. The degradation of the gamma-PGA backbone by gamma-GTP resulted in a dramatic change in nanoparticle morphology. With increasing time, the gamma-PGA nanoparticles reduced in size and finally disappeared completely.Time-course of the changes in the morphology of the gamma-PGA nanoparticles following incubation with gamma-glutamyl transpeptidase.     

Ring‐opening polymerization of ε‐caprolactone and L‐lactide from silica nanoparticles surface

Coating of silica nanoparticles by biocompatible and biodegradable polymers of ε‐caprolactone and L ‐lactide was performed in situ by ring‐opening polymerization of the cyclic monomers with aluminum, yttrium, and tin alkoxides as catalysts. Hydroxyl groups were introduced on the silica surface by grafting of a prehydrolyzed 3‐glycidoxypropyl trimethoxysilane to initiate a catalytic polymerization in the presence of metal alkoxides. In this manner, free polymer chains were formed to grafted ones, and the graft density was controlled by the nature of the metal and the alcohol‐to‐metal ratio. The grafting reaction was extensively characterized by spectroscopic techniques and quantified. Nanocomposites containing up to 96% of polymer were obtained by this technique. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 1976–1984, 2004     

Improved alternate deposition of biodegradable naturally occurring polymers onto a quartz crystal microbalance

The ultrathin polymer films that were composed of biodegradable and naturally occurring chitosan and poly(γ‐benzylglutamate) were stably deposited onto a quartz crystal microbalance (QCM) by alternate immersion of a QCM from their aqueous solutions in the presence of water‐soluble organic solvents as a USS soluble solvent. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 36: 801–804, 1999     

Open-pore biodegradable foams prepared via gas foaming and microparticulate templating

Open-pore biodegradable foams with controlled porous architectures were prepared by combining gas foaming and microparticulate templating. Microparticulate composites of poly(epsilon-caprolactone) (PCL) and micrometric sodium chloride particles (NaCl), in concentrations ranging from 70/30 to 20/80 wt.-% of PCL/NaCl were melt-mixed and gas-foamed using carbon dioxide as physical blowing agent. The effects of microparticle concentration, foaming temperature, and pressure drop rate on foam microstructure were surveyed and related to the viscoelastic properties of the polymer/microparticle composite melt. Results showed that foams with open-pore networks can be obtained and that porosity, pore size, and interconnectivity may be finely modulated by optimizing the processing parameters. Furthermore, the ability to obtain a spatial gradient of porosity embossed within the three-dimensional polymer structure was exploited by using a heterogeneous microparticle filling. Results indicated that by foaming composites with microparticle concentration gradients, it was also possible to control the porosity and pore-size spatial distribution of the open-pore PCL foams.     

Effects of an avidin-biotin binding system on chondrocyte adhesion and growth on biodegradable polymers

Cell adhesion to a scaffold is a prerequisite for tissue engineering. Many studies have been focused on enhancing cell adhesion to synthetic materials that are used for scaffold fabrication. In this study, we applied an avidin-biotin binding system to enhance chondrocyte adhesion to biodegradable polymers. Biotin molecules were conjugated to the cell membrane of chondrocytes, and mediated cell adhesion to avidin-coated surfaces. We demonstrated that immobilization of biotin molecules to chondrocyte surfaces enhanced cell adhesion to avidin-coated biodegradable polymers such as poly(L-lactic acid), poly(D,L-lactic acid), and polycaprolactone, compared to the adhesion of normal chondrocytes to the same type of biodegradable polymer. The biotinylated chondrocytes still maintained their proliferation ability. This study showed the promise of applying the avidin-biotin system in cartilage tissue engineering. [diagram in text].     

Reverse thermal gelation of aliphatically modified biodegradable triblock copolymers

A simple aliphatic modification demonstrated how to turn a water-soluble biodegradable triblock copolymer synthesized from PEG, L-lactide, and epsilon-caprolactone into a thermoreversible polymer of which aqueous solution underwent a sol-to-gel phase transition upon a mild temperature rise. Thermogelling behavior of the aliphatically modified polymer was dependent on the degree of aliphatic modification and polymer concentration. When the polymer solutions were subcutaneously injected into rats, immediate depot formation has been observed. The polymeric gel depots have lasted for two weeks in vivo. This aliphatically modified thermogelling polymer can find applications in drug delivery.     

Facile design of degradable poly(β‐thioester)s with tunable structure and functionality

The synthesis of a range of linear biodegradable poly(β‐thioester)s, PBTs, via hexylamine‐catalyzed thiol‐ene Micheal additions between a variety of diacrylate and dithiol monomers is described. Molecular weights up to 12,000 g mol^?1 are obtained for this new class of polymer materials. PBTs featuring very different chemical and mechanical behavior are obtained on the basis of seven diacrylate and three dithiol monomers. Polar PBTs are synthesized based on ethylene glycol‐containing monomers in an environmentally friendly solvent. Furthermore, PBTs containing urethane units in the main chain are obtained, providing access to an isocyanate‐free polyurethane polymerization method. The thiol‐ene addition approach can also be used to couple polystyrene oligomers synthesized from a bifunctional trithiocarbonate reversible addition fragmentation transfer agent. In this way, PBTs featuring polystyrene segments as well as diacrylate segments are produced. In general for these step‐growth polymerizations, by tuning the stoichiometric monomer ratio, a desired end group functionality can be quantitatively introduced into the PBT, which is demonstrated via soft ionization mass spectrometry analysis. As an example, alkyne end groups have been built in, giving access to use these materials in modular polymer design strategies. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 178–187     

Poly(Lactic Acid)-Based Graft Copolymers: Syntheses Strategies and Improvement of Properties for Biomedical and Environmentally Friendly Applications: A Review

As a potential replacement for petroleum-based plastics, biodegradable bio-based polymers such as poly(lactic acid) (PLA) have received much attention in recent years. PLA is a biodegradable polymer with major applications in packaging and medicine. Unfortunately, PLA is less flexible and has less impact resistance than petroleum-based plastics. To improve the mechanical properties of PLA, PLA-based blends are very often used, but the outcome does not meet expectations because of the non-compatibility of the polymer blends. From a chemical point of view, the use of graft copolymers as a compatibilizer with a PLA backbone bearing side chains is an interesting option for improving the compatibility of these blends, which remains challenging. This review article reports on the various graft copolymers based on a PLA backbone and their syntheses following two chemical strategies: the synthesis and polymerization of modified lactide or direct chemical post-polymerization modification of PLA. The main applications of these PLA graft copolymers in the environmental and biomedical fields are presented.     

Multi‐Stimuli‐Responsive Polymer Materials: Particles,Films, and Bulk Gels

Stimuli‐responsive polymers have received tremendous attention from scientists and engineers for several decades due to the wide applications of these smart materials in biotechnology and nanotechnology. Driven by the complex functions of living systems, multi‐stimuli‐responsive polymer materials have been designed and developed in recent years. Compared with conventional single‐ or dual‐stimuli‐based polymer materials, multi‐stimuli‐responsive polymer materials would be more intriguing since more functions and finer modulations can be achieved through more parameters. This critical review highlights the recent advances in this area and focuses on three types of multi‐stimuli‐responsive polymer materials, namely, multi‐stimuli‐responsive particles (micelles, micro/nanogels, vesicles, and hybrid particles), multi‐stimuli‐responsive films (polymer brushes, layer‐by‐layer polymer films, and porous membranes), and multi‐stimuli‐responsive bulk gels (hydrogels, organogels, and metallogels) from recent publications. Various stimuli, such as light, temperature, pH, reduction/oxidation, enzymes, ions, glucose, ultrasound, magnetic fields, mechanical stress, solvent, voltage, and electrochemistry, have been combined to switch the functions of polymers. The polymer design, preparation, and function of multi‐stimuli‐responsive particles, films, and bulk gels are comprehensively discussed here.     

Investigation of drug release and 1H‐NMR analysis of the in situ forming systems based on poly(lactide‐co‐glycolide)

In situ forming biodegradable polymeric systems loaded with betamethasone (BTM) and betamethasone acetate (BTMA) were prepared using poly(DL ‐lactide‐co‐glycolide) (PLGA), ethyl heptanoate (EH), and N‐methyl‐2‐pyrrolidone (NMP) as the biodegradable polymer, additive, and solvent, respectively. The drug release studies were carried out in buffer (pH = 7.4, 37°C) using high performance liquid chromatography (HPLC). ¹H‐NMR was used to determine the polymer degradation behavior, release mechanism, and interactions between the polymer and drug. The ¹H‐NMR spectra showed that all interactions between the polymer and drug were hydrogen bonding. Hydroxyl groups and fluorine in drugs were involved in hydrogen bonding with PLGA polymer. In ¹H‐NMR studies, we found that the degradation rate in the systems loaded with BTMA was higher than the systems loaded with BTM because BTMA is only slightly soluble and accelerates the hydrolysis of PLGA chains. The formulations loaded with BTM had obviously lower burst release compared with BTMA loaded samples. With respect to ¹H‐NMR spectra, the mechanism of BTM release is controlled by two effective factors: solvent removal and polymer degradation. Copyright © 2008 John Wiley & Sons, Ltd.     

Investigation of a Cu(II)-poly(gamma-glutamic acid) complex in aqueous solution and its insulin-mimetic activity

The complexation between cupric ions (Cu(II)) and poly(gamma-glutamic acid) (gamma-PGA) in aqueous solutions (pH 3-11) has been studied by UV-visible absorption and electron spin resonance (ESR) techniques. Formation of the Cu(II)-gamma-PGA complex is confirmed by the observation of the blue shift of the absorption band in the visible region, anisotropic line shapes in the ESR spectrum at room temperature, and a computer simulation of the visible absorption spectrum of the complex. The structure of the Cu(II)-gamma-PGA complex, depending on the pH, has been determined. The in vitro insulin-mimetic activity of the Cu(II)-gamma-PGA complex is examined by determining both inhibition of free fatty acid release and glucose uptake in isolated rat adipocytes treated with epinephrine, in which the concentration of the Cu(II)-gamma-PGA complex for 50% inhibition of free fatty acid release is very similar to that of CuSO4. However, it is significantly lower than that of a previously reported insulin-mimetic bis(3-hydroxypicolinato)copper(II), [Cu(3hpic)2], complex.     

生物降解高分子/羟基磷灰石复合材料研究进展

由于高分子/HA复合材料兼具HA优良的生物性能和高分子材料良好的力学性能而受到了广泛的重视.本文综述了近年来生物降解高分子/羟基磷灰石复合材料的研究进展,介绍了胶原及其衍生物、聚酯、甲壳素及其衍生物、淀粉等可降解高分子材料与羟基磷灰石复合作为骨修复材料的研究进展,并对此类材料存在的问题和发展前景进行了讨论.