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。     

大蒜素/海藻酸钠/明胶/壳聚糖复合微球的制备及性能

以大蒜素为模型药物,采用复凝聚法制备了海藻酸钠/明胶/壳聚糖复合微球,考察了不同条件对微球溶胀性、载药性能和缓释性能等指标的影响。结果表明,明胶和海藻酸钠(质量比为1∶3)为2%,大蒜素投入量与混合胶比为1∶2时,制备的载药微球(DSGCM)外形规则,粒径分布在0.8~0.9mm之间,载药量为24.3%,包封率为69.4%,复合微球具有p H敏感性,在p H=7.4介质中微球溶胀率达到450%,药物释放过程符合Higuchi方程,明胶的加入可以延缓DSGCM复合微球的药物释放性能。     

响应面法优化海藻酸盐复合凝胶微球的制备工艺条件

以氯化钙(CaCl2)和壳聚糖(CS)作为交联体系,膨润土(BT)作为吸附剂制备了负载甲氨基阿维菌素苯甲酸盐的海藻酸盐(SA)复合凝胶微球,以其载药率(DLR)和平衡溶胀率(ESR)的比值作为响应值(UR,UR=DLR/ESR),采用Box-Behnken设计建立模型和考察海藻酸钠质量分数(1.00~3.00 wt.%)、膨润土质量分数(1.00~5.00 wt.%)、氯化钙浓度(0.10~0.40 mol/L)和壳聚糖质量分数(0.50 ~1.50 wt.%)对响应值的影响。结果表明响应值与四因素关系符合二次模型,在实验范围内,该数学回归模型具有良好的预测性。在各因素设定范围内预测最佳工艺条件为：海藻酸钠浓度2.39 wt.%、膨润土浓度2.81 wt.%、氯化钙浓度0.24 mol/L、壳聚糖浓度0.71 wt.%。在该条件下进行3次重复实验,实际测得的平均响应值为3.5509%,与理论预测值3.5836%无显著性差异。在该条件下制备的复合凝胶微球,包封率为98.31%,载药率为2.11%,并且具有良好的缓释性能。     

响应面法优化海藻酸盐复合凝胶微球的制备工艺

以氯化钙(Ca Cl2)和壳聚糖(CS)作为交联体系,膨润土(BT)作为吸附剂制备了负载甲氨基阿维菌素苯甲酸盐的海藻酸盐(SA)复合凝胶微球,以其载药率(DLR)和平衡溶胀率(ESR)的比值作为响应值(UR,UR=DLR/ESR),采用Box-Behnken设计建立模型和考察海藻酸钠质量分数(1.00%~3.00%)、膨润土质量分数(1.00%~5.00%)、氯化钙浓度(0.10~0.40 mol/L)和壳聚糖质量分数(0.50%~1.50%)对响应值的影响。结果表明,响应值与四因素关系符合二次模型,在实验范围内,该数学回归模型具有良好的预测性。在各因素设定范围内预测最佳工艺条件为:海藻酸钠质量分数2.39%、膨润土质量分数2.81%、氯化钙浓度0.24 mol/L、壳聚糖质量分数0.71%。在该条件下进行3次重复实验,实际测得的平均响应值为3.550 9%,与理论预测值3.583 6%无显著性差异。在该条件下制备的复合凝胶微球,包封率为98.31%,载药率为2.11%,并且具有良好的缓释性能。     

改性蒙脱石对海藻酸钠载药凝胶微球的结构及释药性能的影响

以双十二烷基二甲基溴化铵(DDAB)作为改性剂对钠基蒙脱石进行插层改性,并以此改性蒙脱石吸附啶虫脒,然后包覆在海藻酸钠微球中。通过红外光谱、X射线衍射、扫描电子显微镜和释药实验对改性蒙脱石的结构、形貌和载药微球的释药性能进行了表征。结果表明:经DDAB改性后的蒙脱石的层间距由原来的1.21 nm增加到3.64 nm。改性蒙脱石对农药啶虫脒的吸附能力显著增强;且改性蒙脱石的加入使海藻酸钠凝胶微球的内部呈多孔结构,提高了其对药物的缓释性能,在50 h内微球仅释药约16%,其释药过程符合Non-Fickian扩散模型。     

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.     

凹凸棒黏土对壳聚糖/海藻酸钠微球释放性能的影响

将凹凸棒黏土(ATP)与海藻酸钠(SA)进行复合以改善SA的缓释性能。以ATP/SA复合物为球芯材料,壳聚糖(CS)为包覆材料,采用复凝聚法制备凹土/海藻酸钠/壳聚糖复合微球(ASCM),并以双氯芬酸钠(DS)为模型药物,考察了凹土添加量对复合微球溶胀性能、载药性能和缓释性能的影响。结果表明,凹土的加入改善了微球的溶胀性能和缓释性能,而对微球载药性能影响不大。与海藻酸钠/壳聚糖微球(SCM)相比,当复合微球中ATP/SA(w/w)为20%时,其在pH6.8的磷酸缓冲溶液中2 h的累积释放率由58.8%减小到38.7%。复合微球体外释放动力学数据表明,其释药行为可以很好地用一级动力学方程拟合。凹土的加入有效改善了SA的缓释性能,ASCM可作为缓释药物的载体材料。     

阿维菌素凝胶微球制备及其缓释性能研究

以壳聚糖(CS)和海藻酸钠(ALG)为包封材料,以阿维菌素(AVM)为芯材,采用锐孔法制备了阿维菌素-海藻酸钠-壳聚糖微球,考察了海藻酸钠质量分数、壳聚糖质量分数、氯化钙质量分数和芯壁体积比(质量分数1%的阿维菌素乳液与质量分数3%海藻酸钠溶液的体积比)对微球形态及包埋率的影响,利用SEM、FTIR等对微球结构及性质进行了表征,并考察了其在土壤中的缓释性能和释药机制。结果表明,经优化的制备条件为:海藻酸钠、壳聚糖及氯化钙的质量分数分别为3%、0.6%及5%,芯壁体积比为1∶2,制备的载药微球形状规整,成球性良好,粒径约0.7 mm,载药量31.65%,包埋率83.81%;红外光谱分析显示,芯壁材料之间除氢键外,没有发生化学作用。所制备的阿维菌素微球在土壤中具有缓释特性,42 h累积释药率达到82.06%,之后药物释放减缓。药物释放特性符合Riger-Peppas模型,释放机理为Fick扩散。     

阿司匹林壳聚糖纳米缓释微球的制备及体外释放性能的研究

以自制阿司匹林为药物,壳聚糖为载体,采用乳化-化学交联法制备了阿司匹林-壳聚糖载药微球,确定了阿司匹林-壳聚糖载药微球的制备工艺条件,探讨搅拌速度、阿司匹林/壳聚糖质量比、交联剂戊二醛、乳化剂Span-80用量对微球的药物包封率、载药量和释药性能的影响。研究结果表明,室温条件下,以液体石蜡为介质,选用3%的壳聚糖冰醋酸溶液、按阿司匹林∶壳聚糖=1.5∶1、4%的戊二醛为交联剂、Span-80用量为体积比6%、中等搅拌速度制备出的微球药物包封率可达79%,微球粒径最小可达20 nm,制得的载药微球在16 h内对药物有良好的缓释作用,在25 h之内仍存在缓药效果。     

啶虫脒/脲醛树脂微胶囊的制备及表征

以脲醛树脂为载体,采用原位聚合法制备了啶虫脒/脲醛树脂微胶囊,通过正交实验考察了单体摩尔比、乳化时间、酸化时间、固化时间等对微胶囊载药率、包封率的影响,并对微胶囊的形貌、释药性能和贮存性能进行了表征。结果表明,当尿素与甲醛摩尔比1.0∶1.8、乳化时间1 h、酸化时间1.0 h、固化时间2.0 h时,所得啶虫脒/脲醛树脂微胶囊形态光滑,粒径分布均匀,包封率高且具有良好的缓释效果和贮存稳定性。     

Electrospray preparation of propranolol‐loaded alginate beads: Effect of matrix reinforcement on loading and release profile

In the present study, propranolol loaded‐calcium alginate beads were prepared from concentrated solutions of sodium alginate, using combined method of electrospray and ionotropic gelation. The objectives of the study were to increase the propranolol‐HCl loading and to decrease its initial burst release. However, the effects of voltage, nozzle diameter, flow rate, and concentration of sodium alginate on size of the beads and drug entrapment efficiency (DEE) were also investigated. The matrix of alginate beads was reinforced with dextran sulfate and/or coated with chitosan. The mean particle size of the beads, their swelling behavior, and drug entrapment efficiency were characterized. Furthermore, the drug release profiles from the prepared beads in simulated gastric fluid and intestinal fluid were evaluated and compared. Among the parameters that affected the electrospray of alginate, voltage had a pronounced effect on the size of beads. The size of beads was reduced to a minimum value on increasing the voltage. Furthermore, increasing the flow rate, alginate concentration, and nozzle diameter and decreasing the voltage led to improvement in DEE. Enhancing the alginate concentration as well as coating with chitosan and reinforcing with dextran sulfate led to increase of the encapsulation efficiency and therefore decrease of the drug release rate in both pHs. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41334.     

Tunable transport of glucose through ionically‐crosslinked alginate gels: Effect of alginate and calcium concentration

Alginate beads have numerous biomedical applications, ranging from cell encapsulation to drug release. The present study focuses on the controlled release of glucose from calcium‐alginate beads. The effects of alginate concentrations (1–6 wt %) and calcium chloride concentrations (0.1–1.0M) on glucose release from beads were examined. It was found that the time required for complete glucose release from beads could be tuned from 15 min to over 2 h, simply by varying alginate and calcium chloride concentrations in beads. For calcium‐alginate beads with sodium alginate concentrations of 1–4 wt %, higher sodium alginate concentrations lead to more prolonged release of glucose and thus a smaller value of a rate constant k, a parameter shown to be proportional to the diffusion coefficient of glucose in the alginate gel. For beads with sodium alginate concentrations of 4–6 wt %, there was no statistically significant difference in k values, indicating a lower limit for glucose release from calcium‐alginate beads. Similarly, higher calcium chloride concentrations appear to extend glucose release, however, no conclusive trend can be drawn from the data. In a 50 : 50 mixture of calcium‐alginate beads of two different alginate concentrations (1 and 4 wt %), glucose release showed a two‐step profile over the time range of 20–50 min, indicating that the pattern and time of glucose release from beads can be tuned by making combinations of beads with varying alginate and/or calcium chloride concentrations. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Chitosan/calcium–alginate beads for oral delivery of insulin

A mild chitosan/calcium alginate microencapsulation process, as applied to encapsulation of biological macromolecules such as albumin and insulin, was investigated. The microcapsules were derived by adding dropwise a protein-containing sodium alginate mixture into a chitosan–CaCl₂ system. The beads containing a high concentration of entrapped bovine serum albumin (BSA) as more than 70% of the initial concentration were achieved via varying chitosan coat. It was observed that approximately 70% of the content is being released into Tris-HCl buffer, pH 7.4 within 24 h and no significant release of BSA was observed during treatment with 0.1M HCl pH 1.2 for 4 h. But the acid-treated beads had released almost all the entrapped protein into Tris-HCl pH 7.4 media within 24 h. Instead of BSA, the insulin preload was found to be very low in the chitosan/calcium alginate system; the release characteristics were similar to that of BSA. From scanning electron microscopic studies, it appears that the chitosan modifies the alginate microspheres and subsequently the protein loading. The results indicate the possibility of modifying the formulation in order to obtain the desired controlled release of bioactive peptides (insulin), for a convenient gastrointestinal tract delivery system. © 1996 John Wiley & Sons, Inc.     

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     

Beta cyclodextrin–insulin‐encapsulated chitosan/alginate matrix: Oral delivery system

Cyclodextrins (CD) form inclusion complexes with many drug molecules. The complexed drugs have increased bioabsorption in in vivo system. We have attempted to complex insulin with β‐Cyclodextrin (BCD) and encapsulate in the chitosan/calcium alginate matrix. For drug release studies insulin complexed with BCD for 20 min and that complexed with BCD for 150 min have been used for encapsulation in the chitosan/calcium alginate matrix. The two matrices seem to have different drug release profiles in simulated intestinal medium (pH 7.4) It appears that drug release from the 20‐min BCD complexed system encapsulated in the chitosan/calcium alginate matrix begins only after an hour, where, being released from the 150‐min BCD complexed system it begins in the first hour itself. Also, aggregation of the insulin molecules seems to be reduced by the complexation of the drug with BCD. Another noticeable fact is the change in the loading character, which is found to be inversely related to the concentration of BCD when it is above the stoichiometric equivalent of the drug. In an attempt to increase the payload of the drug in the matrix, the pH of the processing medium consisting of calcium chloride and chitosan is varied. It is found that the encapsulation efficiency increases as the pH is decreased from 6.0 to 4.0. Another way of increasing the loading is studied by decreasing the concentration gradient of insulin in the processing alginate solution and the crosslinking medium consisting of chitosan/calcium chloride. Preliminary animal studies on rabbits seem to be promising. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 75: 1089–1096, 2000     

Preparation and in vitro evaluation of new pH‐sensitive hydrogel beads for oral delivery of protein drugs

New biodegradable pH‐responsive hydrogel beads based on chemically modified chitosan and sodium alginate were prepared and characterized for the controlled release study of protein drugs in the small intestine. The ionotropic gelation reaction was carried out under mild aqueous conditions, which should be appropriate for the retention of the biological activity of an uploaded protein drug. The equilibrium swelling studies were carried out for the hydrogel beads at 37°C in simulated gastric (SGF) and simulated intestinal (SIF) fluids. Bovine serum albumin (BSA), a model for protein drugs was entrapped in the hydrogels and the in vitro drug release profiles were established at 37°C in SGF and SIF. The preliminary investigation of the hydrogel beads prepared in this study showed high entrapment efficiency (up to 97%) and promising release profiles of BSA. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Dual crosslinked carboxymethyl sago pulp/pectin hydrogel beads as potential carrier for colon‐targeted drug delivery

Carboxymethyl sago pulp (CMSP)/pectin hydrogel beads were synthesized by calcium crosslinking and further crosslinked by electron beam irradiation to form drug carrier for colon‐targeted drug. Sphere‐shaped CMSP/pectin 15%/5% hydrogel beads is able to stay intact for 24 h in swelling medium at pH 7.4. It shows pH‐sensitive behavior as the swelling degree increases as pH increases. Fourier transform infrared spectroscopy analysis confirmed the absence of chemical interaction between hydrogel beads and diclofenac sodium. Differential scanning calorimetric and X‐ray diffraction studies indicate the amorphous nature of entrapped diclofenac sodium. The drug encapsulation efficiency is up to about 50%. Less than 9% of drug has been released at pH 1.2 and the hydrogel beads sustain the drug release at pH 7.4 over 30 h. This shows the potential of CMSP/pectin hydrogel beads as carrier for colon‐targeted drug. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43416.     

Preparation,Characterization, and Drug-Release Behaviors of a pH-Sensitive Composite Hydrogel Bead Based on Guar Gum,Attapulgite, and Sodium Alginate

A novel guar gum-g-poly (acrylic acid)/attapulgite/sodium alginate (GG-g-PAA/APT/SA) composite hydrogel bead with excellent pH sensitivity was prepared via a facile ionic gelation approach and characterized by FTIR and SEM techniques. The effect of APT content on the encapsulation efficiency (EE), swelling ratio, and drug release behaviors of the beads was investigated and the in-vitro release kinetics were also evaluated using diclofenac sodium (DS) as the model drug. The results indicate that the burst release effect of DS drug was eliminated due to the incorporation of APT, and the DS cumulative release was clearly decreased with increasing the APT content.     

Biodegradable Nanoparticles-Loaded PLGA Microcapsule for the Enhanced Encapsulation Efficiency and Controlled Release of Hydrophilic Drug

Recently, nano- and micro-particulate systems have been widely utilized to deliver pharmaceutical compounds to achieve enhanced therapeutic effects and reduced side effects. Poly (DL-lactide-co-glycolide) (PLGA), as one of the biodegradable polyesters, has been widely used to fabricate particulate systems because of advantages including controlled and sustained release, biodegradability, and biocompatibility. However, PLGA is known for low encapsulation efficiency (%) and insufficient controlled release of water-soluble drugs. It would result in fluctuation in the plasma levels and unexpected side effects of drugs. Therefore, the purpose of this work was to develop microcapsules loaded with alginate-coated chitosan that can increase the encapsulation efficiency of the hydrophilic drug while exhibiting a controlled and sustained release profile with reduced initial burst release. The encapsulation of nanoparticles in PLGA microcapsules was done by the emulsion solvent evaporation method. The encapsulation of nanoparticles in PLGA microcapsules was confirmed by scanning electron microscopy and confocal microscopy. The release profile of hydrophilic drugs can further be altered by the chitosan coating. The chitosan coating onto alginate exhibited a less initial burst release and sustained release of the hydrophilic drug. In addition, the encapsulation of alginate nanoparticles and alginate nanoparticles coated with chitosan in PLGA microcapsules was shown to enhance the encapsulation efficiency of a hydrophilic drug. Based on the results, this delivery system could be a promising platform for the high encapsulation efficiency and sustained release with reduced initial burst release of the hydrophilic drug.