层状复合氢氧化物的药物控释动力学机制

以层状复合氢氧化物(LDH)为载体组装乙酰苯甲酸(ASP)的插层复合物LDH-ASP,以pH2.48~6.89的磷酸盐溶液为介质进行药物释放动力学实验,通过对不同时间药物释放度的测定及释放药物后载体结构变化分析研究了LDH对层间药物的控制释放机制。结果表明粉末状LDH-ASP能在较宽的pH范围表现明显缓控释作用,药物释放度积分方程与Higchi方程、Ritger-Peppas方程、Bhaskar方程及一级动力学方程等经验模型吻合。复合物与溶出介质的反应机制研究表明,药物释放速率及释放度大小取决于交换配比n(ASP)/n[HnPO4(3-n)-]所决定的LDH层间通道畅阻情况。     

层状复合氢氧化物对乙酰苯甲酸的负载与体外释放

共沉淀-微波晶化法合成层状复合氢氧化物(LDH)后, 用不同方式将乙酰苯甲酸(ASP)组装到LDH层间制成载药体LDH-ASP, 通过对合成及药物释放前后的液相分析与固相表征数据研究了LDH对ASP的负载及载药体LDH-ASP在磷酸盐介质的溶释现象. 结果表明: LDH层间通道是负载、贮存及控制药物释放的微观基础; 载体选择、药物配比、反应能量供给方式及搅拌强度是决定并影响LDH-ASP载药效率的基本因素, LDH-ASP结构参数可以反映药物负载情况、并与其释放性能明确相关; LDH对ASP的负载与释放均致晶胞参数改变、结晶度下降; 载药体与前体的晶态属性、热力学行为及表面特性相似, 而释放药物后固相的晶态性征减弱、无定形性增强、通道吸附活性降低, 有利于使命后载体在体内降解消除.     

布洛芬插层类水滑石/淀粉凝胶复合物的制备及缓释行为

为设计新型布洛芬缓释体系提供实验依据,以氯化镁、氯化铝、布洛芬(IBU)及淀粉等为原料,采取共沉淀-焙烧还原法及冷冻-解冻法,制备了层状双氢氧化物-布洛芬插层复合物(LDH-IBU)、淀粉凝胶-布洛芬复合物(淀粉凝胶-IBU)及层状双氢氧化物/淀粉凝胶-布洛芬插层复合物(LDH/淀粉凝胶-IBU)。 通过傅里叶红外光谱仪(FT-IR)、X射线衍射仪(XRD)表征了上述3种复合物的结构,并研究了它们在模拟人体环境条件下的缓释性能。 结果表明,3种复合物中的IBU在不同的缓释介质中都具有一定的缓释效果,复合物释放速率大小为:LDH/淀粉凝胶-IBU>LDH-IBU>淀粉凝胶-IBU;在pH值为6.6和7.4以及0.9%生理盐水3种缓冲介质中释放速率依次减小。 释放动力学均符合准一级动力学方程。     

喜树碱插层的镁铝型层状双金属氢氧化物的合成及表征

采用共沉淀法把抗癌药物喜树碱（Camptothecin, CPT）插入层状双金属氢氧化物(layered double hydroxide, LDH)层间, 合成了CPT-LDH纳米杂化物。结果表明,在CPT-LDH纳米杂化物中,CPT在层间的排布方式有两种,即平行于层板的单层排列和垂直于层板的双层排列;缓释研究表明,CPT-LDH在pH 7.5的磷酸缓冲液中具有明显的缓释效果,其释放速率较相同pH值时CPT和LDH物理混合物的释放速率明显降低;考察了CPT-LDH的药物释放机理,在 pH 7.5的缓冲溶液中,释放过程受粒内扩散过程控制;CPT-LDH纳米杂化物的释放动力学符合准一级动力学过程。     

5-氟尿嘧啶在pH敏感型分子筛控释载体中的缓释行为

以肠溶性的羟丙基甲基纤维素邻苯二甲酸酯(HPMCP)作为包覆材料,制备了HPMCP包覆的SBA-15介孔分子筛药物控释载体(HPMCP/SBA-15),并考察了抗癌药物5-氟尿嘧啶(5-Fu)负载于控释载体后,在不同pH释放环境中的释放行为.结果表明,在模拟胃液中(pH=1.2),HPMCP能明显地延缓5-Fu的释放速度;药物释放4h后,其释放率仅为15%.而在模拟肠液中(pH=7.5)HPMCP迅速溶解,对5-Fu释放速度的影响甚微;药物释放4h后,释放率可达到80%.与此同时,包覆膜的干燥温度影响5-Fu的释放行为,干燥温度越高,药物在模拟胃液中的释放速度越慢.     

“右旋糖酐-磁性层状复合氢氧化物-氟尿嘧啶”给药系统的超分子组装表征与急毒性水平

用"前体共沉淀-离子交换插层-原位复合-溶剂转换"技术合成"右旋糖酐-磁性层状复合氢氧化物-氟尿嘧啶"(DET-MLDH-FU,DMF)运载系统,通过XRD,IR,TEM,TG表征及体外释放实验研究了DMF的物相特征与缓释性能,通过对小鼠灌胃和腹腔注射给药考察了DMF与载体MLDH的急毒性水平.结果表明,DMF等超分子的XRD与R-六方LDH衍射特征相符,是Fe3.6Fe0.9(O,OH,Cl)9型LDH及微量Fe3O4的复合晶相,DMF具有DET,MLDH与FU分级组装形成的核壳式构造.体外pH 7.35 PBS溶出介质中,DMF的药物释放遵守零级模型C-1.162×10-5=4.566×10-7t,速率常数4.566×10-7 mol-1?L?m-1.DMF,MLDH-FU及MLDH可经正常代谢排出体外,口服毒性小;腹腔注射DMF的LD50为2542.8 mg?kg-1,MLDH的LD50为1951.0 mg?kg-1,均属低毒性物质.DET的复合组装对Fe(II,III)LDH构架有抗氧化保护作用,对不同MLDH-FU粒子进行选择、分离与包封,提高MLDH-FU的缓释效果、强化MLDH的控释性能,降低给药系统DMF的急毒性水平.     

含5-氟尿嘧啶的羧甲基纤维素钠/聚(N-异丙基丙烯酰胺)半互穿网络水凝胶的药物释放性能

以5-氟尿嘧啶(5-FU)为模型药物,对羧甲基纤维素钠/聚(N-异丙基丙烯酰胺)半互穿网络水凝胶(CMC/PNIPA semi-IPN)的药物释放性能进行了研究。结果表明:在37℃、pH=7.4时,药物的释放速率以及释放量都随着凝胶中羧甲基纤维素钠含量的增加而增大。在25℃时,pH对药物释放速率的影响较小;而在37℃时,药物释放速率受pH的影响较大。该凝胶体系用做5-FU的口服释放载体具有较佳的释放性能。     

羟基喜树碱-类水滑石纳米杂化的共组装制备及表征

采用共组装法在水溶液中制备羟基喜树碱(HCPT)-层状双金属氢氧化物(LDH)纳米杂化物.先利用微通道反应器通过共沉淀法制备了Zn₂Al-NO₃ LDH纳米片,然后与羧酸盐型HCPT在水介质中共组装,制备了HCPT插层LDH的纳米杂化物.利用酸处理,可将层间HCPT由非生物活性的羧酸盐型转化为生物活性的内酯型,这对高生物活性HCPT-LDH纳米杂化物的绿色制备具有重要意义.共组装法制备HCPT-LDH纳米杂化物,耗时短、载药量高、分散性好,且利用原料配比可方便地调控载药量. HCPT分子在LDH层间以其长轴倾斜于层板呈双层排列.所制备的HCPT-LDH纳米杂化物具有良好的药物缓释性能,颗粒内部扩散是药物释放过程的控速步骤.药物释放过程可用准二级动力学模型描述.可以用于构筑LDH基药物输送-控释体系.     

水滑石负载 Au 纳米粒子的制备及其催化醇氧化反应

 采用离子交换法和 NaBH4 还原法制备了 Mg-Al-水滑石 (LDH) 负载的 Au 纳米粒子 (Au/LDH) 催化剂. X 射线衍射和透射电镜结果表明, Au 粒子较均匀地分散在水滑石表面, 载体仍保持层状结构. 在温和的反应条件下, Au/LDH 对一系列醇的氧化反应表现出优异的催化性能, 如在室温常压下进行分子 O2 氧化 1-苯基乙醇的反应, 底物转化率和苯乙酮选择性都接近 100%, 而且催化剂经过多次循环使用后, 其活性未见下降. 可见, Au/LDH 催化剂在醇氧化反应中具有良好的应用前景.     

AMS-8-NH2的合成及其对ODN的负载释放

以阴离子表面活性剂肉豆蔻酰基谷氨酸钠(C₁₄GluA-Na)为模板剂, 3-氨丙基三甲氧基硅烷(APS)为辅助结构导向剂, 合成了介孔材料AMS-8-NH₂, 并结合XRD分析、N₂吸附/脱附技术及²⁹Si魔角旋转核磁共振(MAS NMR)等技术手段对纳米孔洞材料AMS-8-NH₂进行了表征. 结果表明, AMS-8-NH₂是高度有序的纳米孔洞材料, 其孔径和比表面积分别为3.2 nm和706 m²/g; 有机胺基团通过化学键连接在材料内表面, 这些基团的覆盖度达到25%. 以AMS-8-NH₂为载体, 寡核苷酸(ODN)为模型生物分子研究在不同条件下AMS-8-NH₂对ODN的吸附和释放性能, 实验结果表明, 当ODN浓度一定时, 溶液的pH值越低, 对ODN的吸附量越大, pH=4.7时对ODN的最大负载量可达214 mg/g; 在释放过程中, 材料对ODN具有较高的缓释能力, 随环境pH值增加, 释放量增加.     

Synthesis and characterization of a novel controlled release nitrogen-phosphorus fertilizer hybrid nanocomposite based on banana peel cellulose and layered double hydroxides nanosheets

In the present study, a novel environment-friendly hybrid nanocomposite of Banana Peel Cellulose-g-poly(acrylic acid)/PVA (BPC-g-PAA/PVA) hydrogel and Layered double hydroxides (LDH) nanosheets was developed using in situ graft polymerization for slow release of NP (nitrogen, phosphorous) fertilizers and water retention. The hybrid nanocomposite hydrogel containing NP fertilizers was characterized using FTIR, and SEM. The effects of pH changes and different saline solutions on the swelling behavior, fertilizer release and water retention properties of the nanocomposite were investigated.The nanocomposite hydrogel showed a pH dependent swelling, as in the pH range of 7–10, the hydrogel had higher water absorbency. However, pH had opposite effects on the release of fertilizers. Phosphorus release had an increasing trend from pH 2 to 7 and it reached its maximum value at normal pH while nitrogen had a higher release rate at acidic pH and by increasing pH from 2 to 7, the release of nitrogen decreased gradually. Water absorption and fertilizer release of hydrogel was influenced by different cations in the order of Ca²⁺ < K⁺ < Na⁺. Water retention study in loamy sand soil showed that the nanocomposite hydrogel significantly improved the water retention of the soil for a longer period of time, compared to neat BPC-gPAA. This result indicated that incorporation of LDH nanosheets in hydrogel matrix improved its water retention property. The obtained results revealed that the nanocomposite of BPC-g-PAA/PVA hydrogel and LDH nanosheets can be a promising controlled release fertilizer formulation with enhanced water retention properties for agricultural applications.     

Fe-Al layered double hydroxides in bromate reduction: Synthesis and reactivity

This study presents a rare use of layered double hydroxides of Fe(II) and Al(III) (Fe-Al LDH), as reported for the first time for bromate removal from aqueous solutions. The Fe-Al LDH samples were prepared with Fe/Al molar ratios of 1-4 using a co-precipitation method at pH 7, with subsequent hydrothermal treatment at 120°C. The Fe-Al LDH (molar ratio of Fe/Al=1, 2) with a layered structure exhibited nearly complete removal of bromate from initial concentration of 100μmol/dm(3) at a wide pH range of 4.0-10.5 over a 2h reaction period; the residual bromate concentration in the solution was lower than the detection limit of 0.07μmol/dm(3) (9μg-BrO(3)(-)/dm(3)). During the reaction period, bromide was released into the solution via a reduction process. Reactivity of Fe-Al LDH with a Fe/Al molar ratio of 2 did not decrease the bromate reduction efficiency during 30days.     

pH响应的介孔二氧化硅纳米颗粒的制备及可控释放

选择带负电荷且溶解度和分子结构对pH值非常敏感的聚丙烯酸作为封堵分子, 采用静电吸附的修饰方法, 制备了pH响应的MCM-41型介孔二氧化硅纳米颗粒. 利用高倍透射电子显微镜(TEM)、 X射线衍射(XRD)、 傅里叶变换红外光谱(FTIR)及比表面积分析等手段表征了介孔二氧化硅纳米颗粒的物理化学性质. 以联钌吡啶染料分子作为模式客体分子, 研究了pH调控下的模式客体分子在介孔二氧化硅纳米颗粒中的包裹及释放行为. 结果表明, 该介孔二氧化硅纳米颗粒对pH具有很好的响应性; 在近中性条件下, 带正电的二氧化硅纳米颗粒通过静电吸附作用吸附带负电的聚丙烯酸, 导致介孔封堵, 使包载的染料分子几乎无释放; 客体分子的释放率随着pH值的降低而升高, 当pH≤5时, 染料分子显著释放, pH=1时客体分子的释放率高达98％, 可以实现对包载客体分子的控制释放. 该pH响应的介孔二氧化硅纳米颗粒载体具有制备简便、 价格低廉和包载量大等优点, 有望应用于药物的控制释放.     

Starch cellulose acetate co-acrylate (SCAA) polymer as a drug carrier

The present study aims to create a controlled-release system through the preparation and characterization of starch cellulose acetate co-acrylate (SCAA) polymer for application as a carrier for cancer drugs. SCA was prepared from maize starch and different ratios of cellulose acetate. The obtained product SCA was reacted with acrylic acid monomer to give cellulose acetate co-acrylate. The best ratio of starch to cellulose acetate was found to be 90:10, giving a stable product with acrylic acid. The cancer drug 8-(2-methoxyphenyl)-3,4-dioxo-6-thioxo-3,4,6,7-tetrahydro-2h-pyrimido[6,1-c]-[1,2,4]triazine-9-carbonitrile was dissolved in dimethylformamide then added gradually at the end of the previous reaction under stirring for 15 min. The prepared polymers with and without the drug were characterized by Fourier-transform infrared spectroscopy. Cuboids discs of the prepared polymer/drug were subjected to drug release in aqueous media at different pH values. The release was measured spectrophotometrically. It was found that the release rate depends on the pH of the aqueous medium as well as on the concentration of the drug loaded onto the polymer carrier. Above pH 12, the polymer containing the drug degraded completely within 1 h after being subjected to alkaline media. Sustained release of drug extended to about 20 days. The amount released depended on the pH of the media in the following order: basic media > acidic media > neutral. According to Higuch’s equation, the diffusion coefficient was found to be 4.2 × 10^?8 and 5.5 × 10^?8 cm s^?1 for the two evaluated concentrations (1.5 and 2 %) of active organic compound (drug).     

Decarbonation of MgAl-LDHs (layered double hydroxides) using acetate-buffer/NaCl mixed solution

By using acetate-buffer (sodium acetate and acetic acid)/NaCl mixed solutions, the deintercalation of carbonate ions (CO(2-)3) was conducted on MgAl--LDHs at different Mg/Al ratios-LDH2 (LDH with Mg/Al approximately 2) and LDH3 (LDH with Mg/Al approximately 3). When only an acetate-buffer solution was used, decarbonation did not take place even if the buffer solution was made acidic enough to dissolve LDH itself; however, the addition of NaCl to the buffer solution caused deintercalation of the carbonate ions from the MgAl-LDHs and the reaction was conducted without any morphological and weight change at 25 degrees C. Under the optimum conditions, full decarbonation was attained for the two MgAl-LDHs in minutes, and the obtained LDHs contained Cl(-) in the interlayer space without incorporation of any acetate anions due to their extremely low anion selectivity of acetate ion. The allowable range for the concentration of the decarbonation solution is wide, and the change in pH due to the decarbonation reaction is slight because of the buffering effect. The decarbonation was affected by the Mg/Al ratio of the LDH; i.e., the present LDH2 was slightly more difficult to decarbonate than LDH3, probably due to the higher layer-charge density of LDH2.     

Synthesis, characterization, and in vitro pH-controllable drug release from mesoporous silica spheres with switchable gates

To accomplish pH-controllable drug release on mesoporous carrier, one of the best ways is to graft stimuli-responsive organic molecules around mesopore outlets. In this work, the pH-responsive propyldiethylenetriamine groups (abbreviative phrase: multiamine chains) were grafted around mesopore outlets of mesoporous silica spheres (MSS) and expected to act as pH-responsive gates. To this end, three multiamine-grafted MSS (i.e., NM1, NM2, and NM3) were synthesized under different reaction temperatures and reaction times. The reaction temperature and time for multiamine grafting were 25 °C and 12 h for NM1, 100 °C and 1 h for NM2, and 100 °C and 12 h for NM3, respectively. Through systematic investigations of TEM, SEM, N(2) adsorption/desorption, TG, and (29)Si MAS NMR, it was found that NM3 had the highest grafting amount of multiamine chains. It was further confirmed that the multiamine chains around the pore outlets of NM3 played the role of "molecular switch" that could well control the transport of guest drug molecules. In contrast, the multiamine chains around the pore outlets of NM2 and NM3 did not show gate effect. The difference should be decided by the fact whether the grafting amount of multiamine chains around mesopore outlets were sufficient under determined reaction temperature and time. In the tests of in vitro drug release, multiamine-gated MSS (i.e., NM3) showed highly sensitive response to the solution pH. At high pH (pH 7.5), ibuprofen (IBU) in this carrier released rapidly and completely within 2 h; at low pH (pH 4.0 or 5.0), only a small part of the IBU (13 wt %) was slowly released from this carrier and the most of IBU was effectively confined in mesopores.     

示差脉冲伏安法测定乳酸脱氢酶活性及纳米微粒生物毒性检测新方法研究

采用示差脉冲伏安法，在乳酸脱氢酶(LDH)酶促体系“丙酮酸盐 + NADH +H⁺ (?) 乳酸盐 + NAD⁺”中，通过检测NAD⁺还原峰电流的变化，测定了不同条件下(不同酶用量、缓冲液pH值以及温度)LDH的活性、酶促体系的米氏常数K_m^NADH以及最大反应速率v_max。并且在最佳实验条件下，通过检测LDH活性的改变，实验考察了3种纳米物质(ZnS，TiO₂(R)和TiO₂(A))对乳酸脱氢酶酶促体系的影响。     

The homogeneous nucleation of 1-pentanol in a laminar flow diffusion chamber: the effect of pressure and kind of carrier gas

The influence of total pressure and kind of carrier gas on homogeneous nucleation rates of 1-pentanol was investigated using experimental method of laminar flow diffusion chamber in this study. Two different carrier gases (helium and argon) were used in the total pressure range from 50 to 400 kPa. Nucleation temperatures ranged from 265 to 290 K for 1-pentanol-helium and from 265 to 285 K for 1-pentanol-argon. Nucleation rates varied between 10(1) and 10(6) cm(-3) s(-1) for 1-pentanol-helium and between 10(2) and 10(5) cm(-3) s(-1) for 1-pentanol-argon. Both positive and slight negative pressure effects were observed depending on temperature and carrier gas. The trend of pressure effect was found similar for both carrier gases. Error analysis on thermodynamic properties was conducted, and the lowering of surface tension due to adsorption of argon on nucleated droplets was estimated. A quantitative overview of pressure effect is provided.     

Poly(PEGDMA‐MAA) copolymeric micro and nanoparticles for oral insulin delivery

Poly(ethylene glycol) dimethacrylate (PEGDMA) and methacrylic acid (MAA) based micro and nanoparticles were prepared and evaluated as a carrier for oral delivery of insulin. PEGDMA was synthesized by esterification reaction of the PEG4000 with MAA in the presence of an acid catalyst. Particles of different size were prepared by emulsion polymerization reaction using different concentration of sodium lauryl sulphate (SLS) as an emulsifying agent. Synthesized copolymeric particle were characterized by attenuated total reflectance‐Fourier transform infrared spectroscopy (ATR‐FTIR), scanning electron microscopy, and acid value. The mean particle diameter of the polymeric micro and nanoparticles at various physiologically relevant pH values was measured using dynamic light scattering. Insulin loading efficiency of the particles was found to be directly proportional to the particle size and inversely proportional to the acid value of the particles. In vitro insulin release studies from various insulin loaded particles were performed by simulating the gastrointestinal tract conditions using HPLC. At pH 2.5, the release of insulin from polymeric particles was observed in the range of 5–8% while a significant higher release (20–35%) was observed at pH 7.4 during first 15 min of in vitro release. Largest size copolymeric particles of 8.3 µm also showed the highest efficiency to reduce the blood glucose level in diabetic rabbits. Copyright © 2010 John Wiley & Sons, Ltd.