改性海藻酸纳米胶囊对氯氟氰菊酯的释放性能

以DCC/DMAP偶联反应将胆固醇基接枝到天然多糖海藻酸钠上,制备了胆固醇基接枝海藻酸钠衍生物(CSAD),采用乳化法对氯氟氰菊酯进行了负载,得到载药纳米胶囊。通过FTIR、1HNMR、荧光光谱、动态光散射、TEM和释药实验分别对改性海藻酸钠的结构和疏水性能以及载药纳米胶囊的形貌结构和释药性能进行了表征。结果表明,改性海藻酸钠的取代度为5.3%⁷.9%,其临界聚集质量浓度由1.23 mg/L降为0.267.9%,其临界聚集质量浓度由1.23 mg/L降为0.26⁰.63mg/L,且随着取代度的增大,疏水基的增多,临界聚集质量浓度降至更低。所制备的载药纳米胶囊的d50为(576.4±7.4)nm。Zeta电位值为(-32.3±0.6)mV,在水溶液中能够表现出极好的稳定性能。对比常规AEO n微乳剂,CSAD的氢键作用是CSAD纳米胶囊具备缓释性能的关键因素。     

海藻酸钠衍生物对水乳液在靶标表面行为的影响

采用反相乳化法制备了以烷基糖苷(APG)为乳化剂的高效氯氟氰菊酯水乳液。测定了药液的动、静态表面张力、接触角以及在香蕉叶片上的持留量和药物吸附量,考察了胆固醇改性海藻酸钠衍生物(CSAD)对载药水乳液在叶片上的润湿性和沉积量的影响。结果表明:室温下,CSAD+APG体系和APG单独体系稳定的水乳液中表面活性剂(APG)的临界胶束质量浓度均为0.1 g/L。当ρAPG=0.1 g/L时,两种体系药液的最大持留量分别为0.010 4和0.007 8 g/cm2,粘附张力分别为24.32和16.14 m N/m,粘附功分别为55.23和46.47 m N/m;在叶片上的药物吸附量分别为524和412μg/L。由此推断:两亲性嵌段聚合物CSAD是通过疏水作用与APG形成混合胶束吸附在固液界面,其有效地提高了药液在叶片上的持留量和药物吸附量。     

毒死蜱/壳聚糖改性凹凸棒土/海藻酸钠微球的制备与缓释性能

采用接枝方法制备了壳聚糖改性凹凸棒土,利用外源挤出法制备了毒死蜱/壳聚糖改性凹凸棒土/海藻酸钠复合微球,利用红外、热重分析和X射线衍射对改性凹凸棒土的结构进行了表征,并研究了改性凹凸棒土对载药微球的载药率、包封率、溶胀性能及缓释性能的影响。结果表明,毒死蜱仍以结晶态存在于复合微球中;壳聚糖改性凹凸棒土复合微球的载药量和包封率均高于相应的酸化凹凸棒土复合微球;加入凹凸棒土降低了载药微球的溶胀率、提高了微球的缓释性能,且壳聚糖改性凹凸棒土在抑制微球溶胀和增强缓释方面优于酸化凹凸棒土;载药微球的释药行为可用HIGUCHI动力学模型来描述。     

海藻酸辛酯衍生物的制备及其载药微纳米胶囊的释药性

以1-溴辛烷为疏水改性剂，采用双分子亲核取代反应(SN2)制备海藻酸辛酯衍生物(OAD)，通过红外光谱(FT-IR)、核磁谱图(1H NMR)对其结构进行鉴定，并采用热重分析(TGA)、X射线衍射(XRD)、荧光光谱(FM)、表面张力(SFT)、透射电镜(TEM)、激光粒度和zeta电位分析仪对其性能进行了表征。 结果表明，辛基侧链的接枝使OAD的分子内氢键断裂，其热稳定性下降，失重率增大，同时伴随其微晶结构的改变。荧光测试中，随聚合物浓度的增大，芘在其溶液中的第一电子振动峰与第三电子振动峰的荧光强度之比(I1/I3)呈现逐步下降的趋势。并且辛基侧链的接枝使海藻酸钠(SA)的临界聚集浓度(CAC)由1.09 g/L降为0.34 g/L，而其SFT也随其浓度的增大而逐步降低，两者同时体现其具有良好的两亲性。 另外，OAD能自聚集形成类胶束的球形结构，相比SA，OAD胶束的水动力学粒径(dH)变小，由255 nm变为193.2 nm，zeta电位也降低，由-36.4 mV降为-39.3 mV，说明OAD具有一定的胶体界面活性. 采用 OAD 胶束负载布洛芬制备载药微纳米胶囊，其对药物的释放具有一定的缓释作用，药物的释放过程属于 Non-Fickian 扩散机制。     

海藻酸辛酰胺协同纳米二氧化硅稳定Pickering乳液

采用辛胺疏水改性海藻酸钠合成了具有两亲性的高分子表面活性剂海藻酸辛酰胺(OAAD),并将其与SiO2纳米颗粒协同制备了稳定的Pickering乳液。通过FTIR、1HNMR、表面张力、荧光光谱、动态光散射、接触角测量、光学显微镜分别对OAAD、OAAD/SiO2纳米颗粒水分散体系和Pickering乳状液的性能进行了表征。结果表明,辛胺氨基成功接枝到海藻酸钠(SA)分子链上,OAAD界面张力较SA降低、临界聚集质量浓度为0.60 g/L,表现出良好的两亲性。将OAAD吸附在SiO2纳米颗粒表面形成的水分散体系用于稳定Pickering乳液时,发现随着OAAD质量浓度增加,SiO2纳米颗粒润湿性增加,Zeta电位减少,粒径增加;而乳液的粒径则逐渐减少,稳定性增强,其机理经初步分析为,当一定浓度的OAAD吸附在SiO2纳米颗粒表面,可导致颗粒间絮凝,从而在油水界面形成网络结构式界面膜,有利于提高Pickering乳液的稳定性。     

乳化法制备海藻酸钙/聚组氮酸微胶囊

采用乳化法制备海藻酸钙微球及海藻酸钙/聚组氨酸载药微胶囊,并考察不同海藻酸钠浓度、氯化钙浓度对微球表面形态、粒径分布、载药性能及微胶囊控制释放性能的影响。结果表明海藻酸钠浓度主要影响微球的粒径大小,氯化钙浓度主要影响微球的分散程度及粒径分布,微球载药量均随海藻酸钠浓度及氯化钙浓度的增加而减小,所制备的微胶囊均无明显的突释现象。     

pH敏感O-羧甲基壳聚糖自组装纳米粒的制备及表征

用5β-胆烷酸(5β-CHA)对O-羧甲基壳聚糖(OCMC)进行疏水改性,接枝磺胺地托辛(SDM)以增强其pH敏感性,在pH=9的磷酸盐缓冲溶液中制备了对肿瘤组织具有靶向潜力的自组装纳米粒子.所得纳米粒粒径在100hm左右,且随5β-CHA接枝量的增加5β-CHA/OCMC纳米粒的粒径减小.自组装纳米粒有较低的临界聚集浓度(10-2 mg/mL),在pH=7.4(人体正常pH)的水溶液中表现出高度稳定性.而当溶液的pH<6.8(肿瘤组织pH)时,接枝SDM的纳米粒子会迅速聚集,粒径剧增,且随SDM接枝量的增加pH敏感性增强.     

猪脾脏转移因子壳聚糖-海藻酸钠微囊的制备及其性能

以壳聚糖-海藻酸钠为囊材,采用乳化-外部凝胶法制备猪脾脏转移因子壳聚糖-海藻酸钠微囊,并研究了其粒径、载药量、包封率、体外释药等性质. 结果表明,经优化工艺所制微囊球形度良好,平均粒径11.05 mm,平均载药量11.60 mg/g,平均包封率60.8%,在磷酸缓冲液(pH=7.4)中的释药曲线方程为ln(1-Q)=-0.0692t-0.6449 (R2=0.9876),符合一级动力学方程. 该制备工艺简单,所制猪脾脏转移因子微囊具有良好的溶胀性能和缓释性能.     

纳米缓释微胶囊的制备及其缓释性能

以海藻酸钠、壳聚糖、啶虫脒为原料,采用高压静电喷雾法制备了纳米海藻酸钠/壳聚糖微胶囊,并采用紫外分光光度计研究了其释药行为。结果表明:纳米海藻酸钠/壳聚糖微胶囊能够实现药物缓释作用,且药物释放比例高达90%。从纳米海藻酸钠/壳聚糖微胶囊释药表现发现其药物释放规律:当波长为250 nm时,吸光度(y)和浓度(x)的定量计算关系为y=0.095 2x-0.000 6,为进一步研究纳米海藻酸钠/壳聚糖微胶囊释药能力的提升奠定了基础。     

两亲性聚乙二醇接枝聚乳酸胶束的制备及特性

制备聚乙二醇接枝聚乳酸(PPLA)聚合物胶束,探讨其作为药物载体的可行性和稳定性。溶剂挥发法制备PPLA胶束并对其表征。萘普生为模型药物,单因素考察了投药量、丙酮用量、加样顺序对包封率的影响。结果表明,PPLA临界胶束质量浓度(CMC)低,为3×10-4g/L;胶束呈球形、平均粒径小于200nm;在室温、稀释、碱性条件下稳定;最佳载药条件为:材料与药物同时溶于丙酮后滴入水中、丙酮与水的体积比1∶10,萘普生与PPLA质量比0.8∶10,PPLA胶束质量浓度1.0g/L。37℃时载药胶束在磷酸盐缓冲液(PBS)中可缓慢持续释放5d以上。结果证明,制备的聚乙二醇接枝改性聚乳酸聚合物胶束可用作疏水性药物的缓释给药载体。     

正渗透膜过程中临界通量的影响因素

临界通量是膜过程中一种重要的污染特性指标.采用阶梯汲取液浓度递增法测定不同污染物、架桥离子浓度及膜面流速对正渗透(FO)膜过程临界通量的影响.结果表明,海藻酸钠(SA)、腐殖酸(HA)及二氧化硅(SiO2)污染时FO膜临界通量值分别为29.32,46.35和32.17 L/(m2·h);随 Ca2+浓度由0 mmol/...     

Design of microcrystalline cellulose-free alginate spheroids by extrusion-spheronization technique

Conventional spheroid preparation by extrusion-spheronization technique requires microcrystalline cellulose (MCC) as processing aid to improve extrudability of wet mass and spheronization capacity of extrudates. The present study investigated formulation and processing attributes in extrusion and spheronization necessary for design of MCC-free alginate spheroids. The physicochemical characteristics of these spheroids were examined and compared against MCC-loaded alginate spheroids using chlorpheniramine maleate and tolbutamide as water-soluble and poorly water-soluble drugs respectively. Alginate spheroids demonstrated a slower release of hydrophilic drug due to ease of matrix swelling and aggregation in the absence of MCC. This reduced their specific surface area for drug dissolution. Crosslinking of alginate with soluble calcium densified the surface of spheroids and hindered matrix aggregation. It led to faster drug release from alginate than alginate-MCC spheroids. Fast drug release was also noted in spheroids embedded with hydrophobic drug when MCC was absent as drug adsorbent. A complete replacement of MCC with alginate can promote or retard drug release of spheroids as a function of drug–polymer interaction and state of matrix swelling and aggregation.     

海藻酸辛酰胺的制备及其协同氨基SiO2纳米粒稳定液体石蜡/水乳液的研究

以辛胺为疏水改性剂,采用酰化法制得具有两亲性的海藻酸辛酰胺(ACA)。将ACA与采用修正Stber法制备的氨基二氧化硅(SiO_2-NH_2)纳米粒混合,在超声的作用下制得O/W型Pickering乳液。通过FT-IR,~1H NMR和荧光光谱对ACA的结构和性能进行表征。并采用激光粒度和Zeta电位分析仪、接触角测量仪和光学显微镜探究了ACA,SiO_2-NH_2及其协同水分散体系的胶体性能和相应的Pickering乳液的形貌。结果表明:ACA的取代度为0.29,在0.15 mol/L Na Cl水溶液中的临界聚集浓度(cac)为0.42 g/L,表现出较强的两亲性能。ACA通过静电作用力成功地吸附于SiO_2-NH_2纳米粒上,使水动力学粒径只有155 nm的SiO_2-NH_2纳米粒增长至386 nm,Zeta电位由+22.2 mV转变为-30.7 mV,在水溶液中能够表现出良好的稳定性。吸附于SiO_2-NH_2纳米粒表面的ACA可以抑制无机纳米粒的聚沉,而游离的ACA形成的胶束结构的疏水内腔能够增溶油滴,减少小油滴的聚并。光学显微镜中出现了粒径较大的Pickering乳液液滴和粒径较小的传统乳液液滴共存的现象,当ACA质量浓度在0.5 cac~1.0 cac时,2种乳液共存现象最为显著。     

载药蒙脱石/海藻酸钠凝胶球的制备和释放性能

以离子交换方式将硫酸氢氯吡格雷插入蒙脱石层间,再用海藻酸钠包衣得到凝胶球。利用XRD、FTIR进行表征以及体外释放实验检测缓释效果。结果表明,硫酸氢氯吡格雷成功地插入蒙脱石层间,蒙脱石的层间距由1.25 nm增大到1.48 nm;体外释放实验显示在1 h内载药凝胶球的累积释放量为12.9%,表明载药蒙脱石/海藻酸钠凝胶球能明显的减少药物突释,因此可将它作为硫酸氢氯吡格雷的缓释载体。     

高岭土的球磨疏水改性及其在海藻酸盐凝胶微球中的应用

为了提高高岭土(KL)对疏水性有机农药的亲和力,以聚甲基氢硅氧烷(PMHS)作为疏水改性剂,采用球磨法改性KL。进而,采用负压冷冻干燥技术将甲氨基阿维菌素苯甲酸盐(EB)负载到改性高岭土颗粒上,然后包覆于海藻酸盐基质中制得载药改性高岭土/海藻酸钙复合凝胶微球(MKL-CA-CMBs)。通过Zeta电位及激光粒度仪、FTIR、SEM、XRD、比表面积及孔径分析仪对改性后KL的结构、形貌和性能进行了表征,同时对MKL-CACMBs的载药和释药性能也进行了考察。结果表明,在球磨机械力作用下,PMHS以物理吸附或化学吸附的方式吸附于KL颗粒表面。改性后的KL粒径减小、比表面积增大,疏水性增强,利于疏水有机农药的负载,使高岭土/海藻酸钙复合凝胶微球(KL-CA-CMBs)的载药率(DLR)和包封率(EE)分别由6.5%和53.1%增长至9.7%和72.5%。MKL-CA-CMBs所具有的缓释性能主要基于MKL对疏水有机农药的亲和能力,剂型的释放模型属于Non-fickian扩散模型。     

海藻酸钙/埃洛石载药微球的制备与缓释盐酸二甲双胍性能

缓释可提高药物利用率,降低其毒副作用。采用交联法制备了海藻酸钙/埃洛石载药微球,以载药微球对盐酸二甲双胍（MH）药物的包封率和缓释效果为考察对象,研究了载药微球的制备工艺和缓释性能,并通过SEM、FTIR和TGA对其结构进行了表征。结果表明：在交联温度为0℃、海藻酸钠用量为1g、埃洛石添加量为2g时,能得到较优的载药微球包封率（79.23%）。上述条件下制得的复合载药微球在pH=6.8的磷酸盐缓冲液中能有效缓释,且720min后缓释度可达85.83%,说明其具有较好的pH敏感性和缓释效果。SEM表明海藻酸钙颗粒与埃洛石在载药微球内部形成复合结构,FTIR表明MH主要以物理包埋的形式于载药微球中,TGA表明添加埃洛石可以提高复合材料在200℃以上的热稳定性。     

Synthesis,and characterization folate-conjugated photocleavable poly(4-substituted-ε-caprolactone) polymers for drug delivery

Abstract

Photo-cleavable polymers containing 5-hydroxy-2-nitrobenzyl alcohol (ONB) junction point between the target molecule of folic acid (FA) and the hydrophobic poly(4-substituted-?-caprolactone) (PXCL_n) chain were synthesized. FA –terminated ONB-PXCL_n polymers formed micelles with critical micelle concentration (CMC) 1.2 – 64.3?mg L^?1. Fluorescence emission spectroscopy indicated the release of Nile red encapsulated FA-ONB-PXCL_n micelles in response to irradiation. Light-triggered bursts released were observed for drug-loaded FA-ONB-PXCL_n micelles. The nanoparticles exhibited nonsignificant toxicity at concentrations up to 300?µg mL^?1. Flow cytometry revealed that the uptake of folate-targeted doxorubicin (DOX) -encapsulated micelles by HeLa cells was faster than that of free DOX.     

Fabrication and characterization of dual drug-loaded poly (lactic-co-glycolic acid) fiber-microsphere composite scaffolds

The purpose of this work is to develop dual drug-loaded poly (lactic-co-glycolic acid) (PLGA) fiber-microsphere composite scaffolds with desired morphologies and dual drug loading properties, and to investigate the release kinetics of the dual drugs, both hydrophobic and hydrophilic, from the composite scaffolds. In this study, simvastatin (SIM) and bovine serum albumin (BSA) were used as model drugs, which were incorporated into the composite scaffolds by performing electrospinning and emulsion electrospraying simultaneously. The optimum condition for electrospraying (solution concentration: 0.06?g/mL; applied voltage: 15?kV; and flow rate: 0.6?mL/h) has been obtained to prepare PLGA microspheres. The release rate of SIM and BSA from the composite scaffolds fit the first order kinetics and the Higuchi model, respectively. The results indicated that fiber-microsphere composite scaffolds had the ability to load two types of drug, suggesting the scaffolds have great potential in the field of tissue engineering and combined therapies.     

Covalently cross‐linked and hydrophobically modified alginic acid hydrogels and their application as drug carriers

Covalently crosslinked and hydrophobically modified alginate hydrogels were prepared through esterification of alginic acid (ALG‐H) with 1,10‐decanediol that functioned as a crosslinking agent and hydrophobic component. The preparation was accomplished with one step and was carried out in N,N‐dimethylformamide solution at a reduced pressure for removing the water produced. The characterization results confirmed the esterification of the products. The modified alginate hydrogels could be used as drug delivery vehicles for controlled release. The drug release study revealed that compared with a calcium alginate hydrogel the modified hydrogels possessed improved loading rate and encapsulation efficiency for the hydrophobic drug(ibuprofen), and a remarkable sustained release behavior was observed. The release kinetics was close to zero order, a desirable drug release pattern. The modified alginate hydrogels were nontoxic and were potentially applicable as a promising biomaterial. POLYM. ENG. SCI., 2013. © 2012 Society of Plastics Engineers