Preparation and Evaluation of Poly-γ-Glutamic Acid Hydrogel Mixtures with Basic Drugs or Acidic Drugs: Effect on Ease of Swallowing and Taste Masking

The purpose of this study was to prepare a poly-γ-glutamic acid hydrogel (PGA gel), to examine its ease of swallowing using texture profile analysis (TPA) and to evaluate its taste-masking effects on basic or acidic drugs using the artificial taste sensor. Using TPA, 0.5% and 1.0% PGA gels, 0.5% and 1.0% agar and 1.0% ι-carrageenan in the absence of drug was examined the hardness, adhesiveness and cohesiveness, ranked according to permission criteria published by the Japanese Consumers Affairs Agency. 0.5% PGA gel and 1.0% agar were classified into grade II. In the taste sensor measurement, the bitterness suppressions by 0.5% PGA gel were larger than that by 1.0% agar in all drugs and the bitterness suppressions of basic drugs in 0.5% PGA gel were more potent than those of acidic drugs in 0.5% PGA gel. 1H-nuclear magnetic resonance spectroscopic analysis was carried out to examine the difference in mechanism of bitterness suppression between basic drugs and acidic drugs mixed with PGA gel. The signals of the proton nearest to the nitrogen atom of basic drugs shifted clearly upfield, suggesting an interaction between the amino group of basic drugs and the carboxyl group of PGA gel. In conclusion, PGA gel is expected to be a useful excipient in formulations contained various drugs, especially basic drugs;it also has advantage for not only increasing ease of swallowing but also masking the bitterness of drugs even though a small amount of a single drug dose might be preferred.

Development of a Freeze-Dried Skin Care Product Composed of Hyaluronic Acid and Poly(γ-Glutamic Acid) Containing Bioactive Components for Application after Chemical Peels

Eight types of spongy sheet were prepared by freeze-drying aqueous solutions of hyaluronic acid (HA) and poly(γ-glutamic acid) (PGA) with or without bioactive components including vitamin C derivative (VC), glucosylceramide (GC), and epidermal growth factor (EGF). Spongy sheets were categorized into the following groups: Group I (HA/PGA), Group II (HA/PGA + VC), Group III (HA/PGA + GC), Group IV (HA/PGA + VC, GC), Group V (HA/PGA + EGF), Group VI (HA/PGA + VC, EGF), Group VII (HA/PGA + GC, EGF), and Group VIII (HA/PGA + VC, GC, EGF). In the first experiment, we examined fibroblast proliferation in conditioned medium that had been prepared by immersing each spongy sheet in a conventional culture medium. EGF-incorporating spongy sheets (Groups V-VIII) enhanced fibroblast proliferation more than EGF-free spongy sheets (Groups I-IV). In the second experiment, cytokine production by fibroblasts was evaluated using a wound surface model. This involved elevation of fibroblasts-incorporating collagen gel sheets to the air-liquid interface, on which a spongy sheet (Groups I, IV, V and VIII) was placed and cultured for 1 week. EGF-incorporating spongy sheets (Groups V and VIII) enhanced the production of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) by fibroblasts more than EGF-free spongy sheets (Groups I and IV). The effect of these four types of spongy sheet on wounds was investigated in animal experiments. Chemical peel was performed by contacting 50% trichloroacetic acid (TCA) on the dorsal region of mice, after which a spongy sheet was placed, and the wound condition was then observed in a two-week period. Angiogenesis was facilitated to a greater degree in Group VIII compared with Groups I, IV and V. This finding indicates that Group VIII spongy sheet is a promising aid for skin recovery after chemical peel.

Combretastatin A4/poly(L-glutamic acid)-graft-PEG conjugates self-assembled to nanoparticles

Combretastatin A4(CA4) possesses varying ability to cause vascular disruption in tumors,while the short half-life, low water solubility and deactivation of many CA4 analogs during storage limited its antitumor efficacy and drug stability. A novel macromolecular conjugate of CA4(CA4-PL) was synthesized by covalent bonding of CA4 onto poly(L-glutamic acid)-graft-polyethylene glycol(PLG-g-PEG) via Yamaguchi reaction. The obtained CA4-PL was characterized by ~1H NMR, GPC, and UV methods, and the properties of the nanoparticles composed of CA4-PL, including critical aggregation concentration, size and size distribution, and morphology, were investigated. CA4-PL can self-assemble to form micelle-like nanoparticles of 80～120 nm in diameter, which may have potential to improve the blood circulation period as well as the targetability of CA4, and find applications to treat various tumors when combined with traditional chemotherapy or radio therapy.

An Anionic Polymer Incorporating Low Amounts of Hydrophobic Residues Is a Multifunctional Surfactant. Part 2: Emulsification, Moisture Absorption, and Moisture Retention of Alkyl Esterified Poly-γ-Glutamic Acid

In the accompanying paper (Part 1), we showed that the fatty acid moiety and the acidity of the polysaccharide-backbone of a fatty acid-containing polysaccharide might be involved in its emul-sification, moisture absorption, and moisture retention abilities. In this study, we synthesized alkyl esterified poly-γ-glutamic acid (PGA) with various chain lengths and degrees of substitution of the alkyl moieties to examine how hydrophobic groups incorporated in the anionic polymer contribute to enhanced emulsification, moisture absorption, and moisture retention. With a low degree of alkylation of PGA, these abilities were drastically improved. To improve the moisture absorption of PGA, alkylation with a short chain length is effective in forming interspaces between PGA chains to trap water molecules. Hydrophobic-hydrophilic balance may also be important to improve the emulsification and moisture retention abilities of PGA alkylates. To the best of our knowledge, this is the first report of the relationship between the structure and the multifunctional abilities of an anionic polymer incorporated with a small amount of hydrophobic residue. PGA alkylates, as well as fatty acid-containing polysaccharides, have potential use as multifunctional surfactants throughout various industries.

锰肥配施γ-PGA对无芒雀麦种子生产的影响

本研究以无芒雀麦(Bromus inermis)为试验材料,在初花期叶面喷施锰肥配施不同浓度γ-聚谷氨酸(γ-PGA)处理,对无芒雀麦的叶绿素含量(SPAD值)、可溶性糖和淀粉含量,以及产量构成因子和种子产量进行了系统的分析。结果表明:包括单穗小花数、单穗种子数、单株小穗数、单株种子数、千粒重和种子产量在内的种子产量构成因子分别提升2.94%~16.47%,,6.86%~16.67%,,8.26%~31.39%,,44.98%~67.37%,,8.40%~12.47%和19.61%~27.98%,其中种子产量最高为623.97 kg·hm^(-2)。锰肥配施γ-PGA后无芒雀麦叶片内SPAD值升高,保证其更有效地进行光合作用而积累更多有机物质,在源、库器官中可溶性糖和淀粉发生积累转移,优先保证生殖器官的生长发育。基于综合评价表明,在无芒雀麦初花期喷施0.05%Mn+1.5%γ-PGA,能够有效提高无芒雀麦的种子产量。

γ-聚谷氨酸和鱼蛋白水溶肥对松花菜生长和产量的影响

为明确γ-聚谷氨酸和鱼蛋白水溶肥在蔬菜生产上的作用,以松花菜为供试作物,设置常规施肥、γ-聚谷氨酸、鱼蛋白3个处理。试验结果表明,γ-聚谷氨酸处理和鱼蛋白处理都能显著提高松花菜的株高、茎粗,提升松花菜品质和产量,增加松花菜的经济效益,以鱼蛋白处理对松花菜增产增效效果更好。

根施γ-聚谷氨酸对烤烟根系活力及烟叶产量和品质的影响

【目的】研究γ-聚谷氨酸(γ-PGA)对烤烟根系发育及烟叶产量和品质的影响,为其在烤烟生产中的合理应用提供理论依据。【方法】在河南卢氏县和洛宁县进行大田试验,设置在移栽时(T1)、团棵期(T2)、移栽时+团棵期(T3)浇灌γ-PGA原液(用量15 L/hm^(2))200倍稀释液,以浇灌等量清水的处理为对照(CK),于移栽后30和60 d测定0~10,10~20 cm土层土壤的含水率,于移栽后30,60和90 d测定根系体积和活力,于烤烟圆顶期测定烟株农艺性状及根、茎、叶干物质质量,在烟叶收获烘烤后测定其经济性状和化学成分,分析各处理土壤水分以及烤烟根系发育、干物质积累及烟叶产量和品质的差异。【结果】浇灌γ-PGA处理能显著提高0~20 cm土层土壤含水率,以T3处理效果最好。与CK相比,施用γ-PGA显著提高了烤烟根系体积和生育前中期烟株的根系活力,在移栽后60 d,T1、T2、T3处理烤烟根系体积较CK增幅分别为39.15%~43.64%,47.38%~73.64%和62.92%~93.41%,根系活力增幅分别为39.01%~39.98%,36.33%~46.32%和51.72%~54.98%。施用γ-PGA显著增加了烟株全株干物质积累量,提高了烤后烟叶的产量、产值、上等烟比例和还原糖含量、糖碱比、钾氯比,改善了烤烟化学成分的协调性,且均以T3处理效果最好,其全株干物质积累量、产量、产值、上等烟比例较CK分别提高了25.20%~46.60%,13.49%~20.79%,27.83%~31.89%和8.14%~12.72%。【结论】在豫西烟区于移栽时、团棵期2次浇灌γ-PGA溶液对烤烟促生增产提质效果最佳。

聚-γ-谷氨酸对黄瓜产量和果实品质的影响

本文研究了复合肥与聚-γ-谷氨酸(poly-γ-glutamic acid,γ-PGA)的不同配方处理对黄瓜产量和果实品质的影响。结果表明,与对照相比,处理3(复合肥配施150 mL/L、3.5%的PGA发酵液)和处理4(复合肥配施300 m L/L、3.5%的发酵液)能使果实长度增加,果形均匀一致,亮度增加,果实表面更富有光泽,果实产量提高;与对照相比,这两组处理后黄瓜产量分别提高了53.2%和47.1%,且单株挂果数极显著提高(P<0.01)。在黄瓜的内在品质上,γ-PGA也有增益作用。可见,γ-PGA与N、P和K的配合及使用,有利于提高黄瓜的生产效益。

枯草芽孢杆菌HG-02聚谷氨酸发酵条件优化

筛选得到了一株高产γ-聚谷氨酸的枯草芽孢杆菌HG-02。通过单因素试验和正交实验对发酵培养基和培养条件进行了优化,小试发酵验证结果显示,优化后γ-聚谷氨酸的发酵质量浓度达35.9 g/L。优化后的发酵培养基为:蔗糖4%,蛋白胨3.5%,谷氨酸钠6%,硫酸镁0.1%,氯化钠0.5%,氯化钙0.01%,磷酸氢二钾0.05%,硫酸锰0.02%,消泡剂1%。优化后的培养条件为:初始pH7.0,装液量40%,接种量6%,摇床转速为220 r/min,37℃恒温培养48 h。

高吸水性聚合物γ-聚谷氨酸对砂壤土水分运移的影响

高吸水性聚合物γ-聚谷氨酸(γ-PGA)又名纳豆胶,是一种节水材料和土壤改良剂,目前已被广泛应用于农业生产。采用室内试验和数值模拟相结合的方法,研究了γ-PGA施用量、施用深度和土壤容重对砂壤土水分入渗特性的交互影响。结果表明,累积入渗量随γ-PGA施用量的增加而减小,入渗率随γ-PGA施用量的增加而减小,Philip入渗模型的吸渗率S和入渗率A值均随土壤容重和γ-PGA施用量的增加而降低;土壤中施加γ-PGA后,饱和含水率θs随γ-PGA施用量的增加而递增,θs增幅为3.15%~10.77%,各处理残余含水率θr变幅为0.031~0.033,其变化不显著,进气吸力值α有明显降低,其极差为0.004 6,n值随γ-PGA施用量的增加而降低,其极差为0.13;土壤容重和γ-PGA施用深度对累积入渗量的影响较γ-PGA施用量更明显。

Preparation and Characterization of Poly(γ-glutamic acid) Hydrogels as Potential Tissue Engineering Scaffolds

In this paper, methacrylated γ-PGA（m PGA） precursor was synthesized via reaction between γ-PGA and glycidyl methacrylate（GMA）. Hydrogels from this precursor were prepared under 365 nm ultraviolet irradiation. The swelling behavior and mechanical properties were studied in detail as functions of the degree of substitution（DS）, precursor concentration, and environmental p H. Results showed that the crosslink density, swelling kinetics and mechanical properties of the hdyrogel could be tailored by adjusting the DS and concentration of the precursor as well as the environmental p H. Three-dimensional photo-encapsulation of swine cartilage chondrocytes and Live/Dead assay proved the cytocompatibility of the hydrogel.

Recovery of rare-earth metal neodymium from aqueous solutions by poly-γ-glutamic acid and its sodium salt as biosorbents:Effects of solution pH on neodymium recovery mechanisms

For recovery of metals from low-concentration sources, biosorption is one of promising technologies and poly-γ-glutamic acid（γ-PGA） has been known as a potential biosorbent for recovery of heavy metals from aqueous solutions. Effects of solution pH on recovery of rare-earth metal Nd are systematically examined to clarify mechanisms of Nd recovery by y-PGA and its sodium salt（y-PGANa）. The recovery efficiency of Nd by y-PGA increases from 2.4 to 19.6% as pH increases from 2 to 4. Subsequently the Nd recovery efficiencies for y-PGA and y-PGANa remain almost constant in the range of pH from 4 to 7. For pH 〉 7 the increase in Nd recovery is significant and 100% recovery of Nd is achieved at pH 9. The pH dependency on Nd recovery by y-PGANa is similar to that by y-PGA. Contributions of adsorption and precipitation/coagulation to Nd recovery process are quantified. Whereas the adsorption dominates Nd recovery at lower pH（〈～4）, the precipitation/coagulation controls Nd recovery process for pH 〉 7. At higher pH, purple gel precipitates are observed. The maximum adsorption capacities for γ-PGA and yPGANa are 215 mg-Nd/（g-γ-PGA） at pH 4 and 305 mg-Nd/（g-y-PGANa） at pH 3, respectively. From the spectra of FT-IR and XPS, the biosorption of Nd onto y-PGA and y-PGANa via electrostatic interaction with carboxylate anions at pH 3 is verified. The Nd complexation with amide and carboxylate anion groups on γ-PGA and γ-PGANa may also contribute to the Nd recovery. The biosorption isotherms for Nd recovery by γ-PGA and γ-PGANa can be satisfactorily fitted by the Langmuir model. The thermodynamic studies suggest that the biosorptions of Nd by γ-PGA and γ-PGANa are endothermic. The utilization of γ-PGA and γ-PGANa as potential and eco-friendly biosorbents for the highly effective recovery of Nd from aqueous solution is confirmed.

Safety and photochemotherapeutic application of poly(γ-glutamic acid)-based biopolymeric nanoparticle

The safety of nanomaterials, a crucial consideration for clinical translation, is enhanced by using building blocks that are biologically nontoxic. Here, we used poly(γ-glutamic acid)(γ-PGA) and dopamine as building blocks of polymeric nanomaterials for carrying hydrophobic anticancer drugs. The introduction of phenylalanine onto γ-PGA enabled the resulting amphiphilic derivative of γ-PGA acid to self-assemble in the presence of the anticancer drug paclitaxel(PTX) to form PTX-encapsulated micelles.The surfaces of PTX-loaded micelles were then coated with polymerized dopamine(PDA). The PDAcoated, amphiphilic γ-PGA-based micelles(AM) carrying PTX(PDA/AM/P) exerted near-infraredresponsive photothermal effects. Near-infrared irradiation of cancer cells treated with PDA/AM/P nanoparticles produced a greater anticancer effect than that observed in other treatment groups, indicating a synergistic effect. Intravenous administration of PDA/AM/P completely ablated tumors and prevented their recurrence. Notably, the in vivo safety profile of PDA/AM/P nanoparticles allowed PTX to be delivered at a 3.6-fold higher dose than was possible with PTX solubilized in surfactant, and circumvented the side effects of the surfactant. These results support the multifunctional potential of PDA/AM for the delivery of various hydrophobic drugs and imaging dyes for safe translation of nanomaterials into the clinic.

Adsorption of La^(3+) and Ce^(3+) by poly-γ-glutamic acid crosslinked with polyvinyl alcohol

With the exploitation of rare earth ore, more and more rare earth elements came into groundwater, caused waste of resources and toxicity to the organisms. This study aimed to find an efficient adsorption material to mitigate the above issue. Through doping polyvinyl alcohol with poly-γ-glutamic acid, an immobilised PSP gel particle was produced and had the adsorption rate of La3＋ up to 97.10%. The factors including initial concentration of La3＋ or Ce3＋, adsorbent dosage, pH and temperature of the solution, which potentially affected the adsorption rate and were studied in batch mode. It was found that the optimum adsorption conditions were composed of 50 mg/L La3 VCe3＋ of initial concentration, 600 mg/L （dry mass） biomass for adsorption, pH 6, temperature 30 ℃, 150 r/min rotational speed, and 1 h adsorption time. The selective adsorption of 15 different rare earth ions in mixed aqueous solu- tions were investigated. However, no significant selective differences were observed. Scanning electron microscopy showed that the morphological characteristic of the novel gel was its porous structure, while polyvinyl alcohol gel had a compact structure. Fourier transform infrared spectroscopy suggested that carboxyl groups in the poly-γ-glutamic acid might played a key role in the adsorption process. The adsorption mechanism forecasted to be cation exchange between -COOH and R3＋. The adsorption kinetic and thermodynamic process for La3＋ and Ce3＋ was consistent with the pseudo-second-order equation and Langmuir adsorption isotherm model. It demonstrated that PSP gels particles were useful for removing REEs from wastewater.

γ-聚谷氨酸的生物合成及应用

聚谷氨酸是一种可降解的生物高分子 ,可由微生物生物聚合而得到。综述了聚谷氨酸的生物合成方法、高吸水性聚谷氨酸制备技术以及在农业、医药。

肥料增效剂γ-聚谷氨酸对小青菜产量和品质的影响

研究了γ-聚谷氨酸(γ-PGA)肥料增效剂对盆栽小青菜产量和品质的影响。结果表明:正常施肥条件下,施用50 mg/kg的γ-PGA可以显著提高小青菜叶绿素、地下部鲜质量,使小青菜地上部鲜质量最大增产幅度达8.8%,与对照相比差异显著;同时还可以明显提高土壤铵态氮的含量,氮肥利用率增加10.6%。施用100 mg/kg的γ-PGA与对照相比,可降低小青菜中的硝酸盐含量44.8%,维生素C(Vc)含量提高18.1%,小青菜品质达到最好;当减施15%质量的氮肥时,20 mg/kg的γ-PGA可提高氮肥利用率10.2%～11.6%,说明在肥料缺乏时γ-PGA对小青菜产量、品质的改善效果显著。

γ-聚谷氨酸高产菌株筛选及发酵条件优化

γ聚谷氨酸是一种生物可降解的高分子材料,可应用于多种领域,因此受到普遍重视。报道了以11株枯草芽孢杆菌菌株为培养菌株,用3种谷氨酸钠含量不同的培养基进行筛选获得1株γ聚谷氨酸高产菌株;再以该菌株为研究对象进行碳源、氮源、谷氨酸钠浓度、初始pH、接种量、通气量等发酵条件的优化实验,结果表明最佳发酵条件为:250ml三角烧瓶装液40ml,接种体积分数5%,麦芽糖50g/L,酵母膏10g/L,谷氨酸钠30g/L,NaCl10g/L,KH2PO45g/L,MgSO4·7H2O0.5g/L,初始pH6.0,发酵60h,此时γ聚谷氨酸产量最高,达到30.26g/L,比国外报道的20g/L的产量有显著提高。纯化后产物经红外光谱及核磁共振检测,鉴定为γ聚谷氨酸。

产γ-聚谷氨酸菌株的筛选及其对玉米幼苗生长的影响

从土壤样品中分离和筛选到1株γ-聚谷氨酸(poly-γ-glutamic acid,γ-PGA)高产菌株C1。经形态、生理生化和16S rRNA序列分析,将C1鉴定为枯草芽孢杆菌。水培试验表明:添加γ-PGA对全养分条件下玉米幼苗生物量增长没有明显的影响,但显著提高了1/2和1/4养分条件下玉米幼苗地上部和地下部生物量。γ-PGA在各种养分条件下都能提高叶绿素相对含量(SPAD值)和根系活力,但1/2和1/4养分条件下提高作用更显著。当γ-PGA浓度低于0.30 g.L-1时,生物量和SPAD值随γ-PGA浓度增加而增加;添加γ-PGA处理的玉米根系活力始终高于对照且与γ-PGA添加量无关。本研究首次揭示了较低浓度的细菌源γ-PGA对低营养条件下玉米的生长有显著的促进作用。

高分子量的聚L-谷氨酸的合成与表征

采用三乙胺为催化剂经过氨基酸羧酸酐单体的开环聚合和脱保护基，制备了高分子量聚L-谷氨酸．实验结果表明。合成的高分子量聚L-谷氨酸黏均分子量控制在70000-350000左右．单体和引发剂的摩尔比n（A）／n（I）大于50时。分子量与n（A）／n（I）无关．

白氨酸-谷氨酸甲酯-谷氨酸共聚物的合成研究

本文研究了白氨酸－谷氨酸甲酯－谷氨酸共聚物的合成方法，先对谷氨酸进行苄酯和甲酯保护，再与光气溶液反应制备氨基酸酯的羧酸酐，共聚合，随后用溴化氢脱酯，由停放时间来控制游离侧羧基含量。红外光谱和紫外吸光度分析表明，反应失去绝大部分的苄基和部分的甲基。与溴化氢作用的时间越长，脱苄的程度越高，游离侧羧基含量越大，其亲水性越强。