交联海藻酸钠磁性微球的制备及固定化胰蛋白酶研究

制备了交联海藻酸钠磁性微球,并以磁性微球为载体,戊二醛为交联剂,将胰蛋白酶固定化;利用透射电镜、粒度分析、红外分析对交联海藻酸钠磁性微球进行了表征;探讨给酶量、戊二醛浓度和pH值对固定化酶活性的影响;与自由酶比较,考察了固定酶的酶学性质.结果表明:交联海藻酸钠磁性微球是固定化胰蛋白酶的良好载体,固定化酶最适宜的条件是吸附时间12h,给酶量为100mg/0.1g磁性载体、交联剂戊二醛浓度为5%、溶液pH值为6,同时将酶固定化后,酶的稳定性和催化性能均有所提高.     

阿霉素磁性海藻酸钠纳米微球的制备与性能

为了增强化疗药物靶向治疗肿瘤效果,减少毒副作用,本文采用微乳方法制备了负载阿霉素的磁性靶向药物微球.系统考察了海藻酸钠、乳化剂浓度、药物投入量等因素对所制微球性质的影响,并对微球的性能进行了表征.结果表明,选择最优化的制备条件,可得平均粒径约为185nm、外观为球型、铁含量为16.5%、载药量为¨.9%的阿霉素磁性纳米微球.该微球具有强磁响应性和长时间药物缓释效果.这种阿霉素磁性纳米微球粒径小,分散性好,具有磁靶向功能,有望成为一种优良靶向肿瘤的药物载体.     

茶多酚/壳聚糖/海藻酸钠纳米微球的制备

目的探讨各因素对制备茶多酚/壳聚糖/海藻酸钠纳米微球载药率、包埋率的影响,研究纳米微球体外释放行为,为后期缓释抗菌膜的制备提供基础。方法采用单因素实验、正交实验考察海藻酸钠溶液浓度、壳聚糖溶液浓度、CaCl_2溶液浓度、茶多酚溶液浓度对纳米微粒载药率、包封率的影响,并考察其体外释放率。结果当海藻酸钠溶液、壳聚糖溶液、CaCl_2溶液、茶多酚溶液的质量浓度分别为15,10,15,0.8 mg/m L时,该工艺条件下制备的纳米微粒载药率为22.71%,包封率为61.38%,且粒径集中在500 nm左右,有较好的缓释效果。结论所得的最佳工艺制备条件为后期做缓释抗菌膜打下良好基础。     

载当归羧甲基纤维素-海藻酸钠复合微球的制备和表征

采用W/O乳液法,在不同条件下,用Ca2+交联和戊二醛交联制备了羧甲基纤维素(CMC)-海藻酸钠(SA)复合微球。SEM结果显示,当m(CMC)∶m(SA)=1∶5、温度为60℃时,球形较好。采用FT-IR分析了复合微球的化学结构。对复合微球的溶胀率、药物包封率进行表征,结果显示复合微球在磷酸缓冲液中的溶胀率达到700%,且溶胀速度快。该复合微球对当归(ASD)具有较好的缓释作用。     

预交联法制备海藻酸钠复合微球及其缓释性能

采用预交联法制备海藻酸钠(SA)/凹土(ATP)复合微球(PCM)以克服常规制备方法导致微球交联不均匀的缺陷,从而改善微球的缓释性能。将ATP先与Ca~(2+)进行部分离子交换制备Ca~(2+)-ATP,然后在与SA复合过程中同时进行预交联形成交联密度有所提高的微球内核,再采用滴注法制备该复合微球。利用红外光谱、扫描电镜和电子照片对微球结构和形貌进行表征,考察了Ca~(2+)浓度对PCM力学强度、溶胀率、载药和缓释性能的影响。结果表明,PCM在1h的累计释放率由预交联前的68%降为50%,显著改善了微球的"突释"。释放动力学研究表明,微球的释药可用Ritger-Peppas方程很好地拟合,释药速率受骨架溶蚀和药物扩散双重控制。     

新型磁性海藻酸钠复合微球的制备与表征

以碳包铁(Fe@C)纳米粉作为磁性内核,用海藻酸钠作表层高分子,以正庚烷为油相,AOT为表面活性剂,氯化钙、环氧氯丙烷作交联剂,通过反相微乳法制备出了碳包铁/海藻酸钠核壳微球,系统考察了海藻酸钠的浓度、交联剂用量等对所制复合纳米微球性质的影响,并对产物进行了初步的性能表征.结果表明,选择合适的海藻酸钠的浓度、交联剂用量和其它相关参数,可以制备出外观为球形、分散性好、平均粒径约为250nm、具有强磁响应性的复合微球.     

纤维素-海藻酸钠-海泡石多孔微球的制备及其对亚甲基蓝吸附性能

以微晶纤维素(Microcrystalline cellulose,MCC)和海藻酸钠(Sodium alginate,SA)为网络框架,海泡石(Sepiolite,SEP)为功能单元,采用悬浮液滴法构建纤维素-海藻酸钠-海泡石(MCC-SA-SEP)双网络多孔复合微球。通过SEM和TG对复合微球结构和热稳定性能进行表征,并研究该微球对亚甲基蓝(Methylene blue,MB)水溶液的吸附性能。结果表明,MCC-SA-SEP复合微球呈现三维网络多孔结构,且随着SEP含量的增加热稳定性逐渐提高。吸附结果显示MCC-SA-SEP符合准二级动力学模型和Langmuir等温线,对MB的饱和吸附容量高达333.3 mg/g。经过五次再生循环后,对MB吸附能力仍能维持85.4%,表明该多孔复合微球可以作为一种高效可再生的有机-无机复合吸附剂用于染料废水处理。      

聚氨酯/淀粉复合微球的制备及药物释放性能研究

采用预聚-扩链-中和-分散法合成聚氨酯(PU)水溶液,将PU与淀粉(ST)溶液按照不同质量比进行复合,采用凝聚相分离法制备PU/ST复合微球;用傅立叶变换红外光谱(FTIR)、扫描电子显微镜(SEM)对微球进行表征,并以盐酸四环素为模型药物制备载药复合微球,初步研究了载药PU/ST复合微球的药物释放性能.结果表明,微球...     

低密度碳空心微球的制备及酚醛树脂空心微球复合材料的性能

以BJO-0930酚醛树脂空心微球为原料,通过酸洗、预氧化、碳化三步工艺,成功制备球形度好、强度高的碳空心微球,并与热固性酚醛树脂复合,热压成型得到轻质酚醛树脂/空心微球复合材料。系统考察了碳化温度、循环酸洗、预氧化等对碳空心微球强度的影响。复合材料的力学性能和隔热性能分别通过压缩性能以及热导率测试进行表征。结果表明:直接碳化得到的碳空心微球破球率高、强度低;通过循环酸洗可以有效去除树脂球的灰分,破球率由28.07%降低至18.03%;进一步预氧化处理可以显著提高碳空心微球的强度,其破球率和等静压破球率分别为10.03%和17.34%;制备得到的酚醛树脂/碳空心微球复合材料具有优异的隔热性能和力学性能,热导率降低至0.115 W·m~(-1)·K~(-1),压缩强度为46.02MPa。     

SA／GT／CS复合水凝胶载药微球的制备与药物释放性能研究

将海藻酸钠/明胶/盐酸四环素共混液滴入含有CaCl2的壳聚糖醋酸溶液中,制备出SA/GT质量配比分别为10/0.6、10/0.8、10/1.0的SA/CS/GT复合水凝胶载药微球,考察了模拟肠液和胃液中不同原料配比对载药性能的影响.结果表明,在配比为10/0/8下微球具有最大载药量,模拟肠液中水凝胶微球释放药物周期较长.因此,SA/CS/GT三元复合水凝胶微球由于其良好的控制释放和降解性能,将是口服释药系统的一种优良载体.     

自修复氧化海藻酸钠-羧甲基壳聚糖水凝胶的制备及药物缓释性能

本研究基于动态亚胺键合成了一种具有自修复性能的氧化海藻酸钠-羧甲基壳聚糖水凝胶(OSA-CMCS).通过海藻酸钠的糖醛酸,合成了OSA,并通过与CMCS的席夫碱反应制备了具有不同交联度的自修复OSA-CMCS水凝胶,研究了OSA-CMCS水凝胶的微观形态、黏弹性能、溶胀性能、自修复性能、酶促降解性能和体外药物释放性能....     

pH-sensitive sodium alginate/calcined hydrotalcite hybrid beads for controlled release of diclofenac sodium

Objective: The aim of this study was to prepare pH-sensitive sodium alginate/calcined hydrotalcite (SA/CHT) hybrid bead with improved the burst release effect of the drug.

Materials and methods: A series of pH-sensitive SA/CHT hybrid beads were prepared by using Ca²⁺ cross-linking in the presence of diclofenac sodium (DS) and SA. The structure and drug loading of the beads were characterized by Fourier transform infrared spectroscopy and X-ray diffraction. The swelling and the drug release of the fabricated beads were investigated by the pH of test medium and CHT content.

Result: The formed positively charged hydrotalcite layers were adsorbed on the negatively charged SA polymer chains through electrostatic interaction and act as inorganic cross-linkers in the three-dimensional network. Compared to pure SA beads, the incorporation of CHT enhanced the drug encapsulation efficiency, improved the swelling behaviors and slowed the drug release from the hybrid beads.

Discussion and conclusions: The electrostatic interaction between hydrotalcite and SA has restricted the movability of the SA polymer chains, and then slowed down swelling and dissolution rates in aqueous solutions. The results provided a simple method to moderate drug release and matrix degradation of the SA beads.     

Preparation of chitosan–sodium alginate microcapsules containing ZnS nanoparticles and its effect on the drug release

Chitosan–sodium alginate microcapsules were prepared in the presence of ZnS nanoparticles via the W/O/W emulsification solvent-evaporation method. Microscopy showed that the microsphere was about 150 nm and by the absorption spectra, ZnS nanoparticles incorporated was 4 nm. Aspirin was chosen to investigate the effect of microcapsules on the drug release. It reveals that comparing with the microsphere without nanoparticles, the release speed of microsphere containing ZnS nanoparticles is significantly decreased from complete release at 10 h to 50% release by 50 h. The data of release kinetics for the microcapsules can be well fitted by the classic Higuchi model.     

氧化海藻酸钠交联壳聚糖载药复合体系的制备及其药物缓释初步研究

为获得一种新型的药物释放复合体系,本实验首先通过乳化交联法制备壳聚糖(CS)包载四环素(TC)微球,然后利用氧化海藻酸钠交联聚磷酸钙/壳聚糖(CPP/CS)复合材料,用冷冻干燥法制备了载药微球复合体系.并用傅立叶红外光谱仪(IR)、扫描电镜(SEM)及药物的体外释放等方法对该载药微球复合体系进行分析和表征.结果显示,经...     

Preparation of novel porous starch microsphere foam for loading and release of poorly water soluble drug

Background: Organic porous material is a promising carrier for enhancing the dissolution of poorly water soluble drug. The aim of the present study was to enhance dissolution and oral bioavailability of lovastatin (LV) by preparing a porous starch microsphere foam (PSM) using a novel method, meanwhile, looking into the mechanism of improving dissolution of LV.

Methods: PSM was prepared by the W/O emulsion – freeze thawing method. The porous structure of PSM was characterized by scanning electron microscopy (SEM) and nitrogen adsorption/desorption analysis. The adsorption role of nanopores on the drug dissolution and physical state of LV was systematically studied by instrumental analysis, and in vitro and in vivo drug dissolution studies. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to evaluate carrier cytotoxicity.

Results: The SEM images of PSM showed nanometer-sized pores. Physical state characterization indicated that porous structure effectively limited the degree of crystallinity of LV. The results of in vitro and in vivo tests testified that PSM accelerated the release of LV and enhanced its oral bioavailability in comparison with crude LV and commercial capsules. The loaded PSM powder indicated a good physical stability under storage for 12 months. MTT assay shows PSM has no toxicity for Caco-2 cell.

Conclusion: The preparation was a promising method to produce small and uniform PSM with markedly enhanced dissolution rate and oral bioavailability due to the spatial confinement effect of porous structure. The present work demonstrates the significant potential for the use of PSM as a novel delivery system for poorly water soluble drugs.     

The role of fillers and sodium metabisulfite on drug release from aged polyox tablets

Polyethylene oxides (PEOs) are extensively used to control the release rate of drugs from matrices. Unfortunately, polyox polymers are prone to oxidation under high temperature and relative humidity. The aim of this study was to investigate the effect of sodium metabisulfite as an antioxidant to overcome the drug release changes from polyox matrices (PEO 301 and 303) when stored at 40?°C. The effect of different types of fillers (lactose, mannitol and dicalcium phosphate dihydrate) on stability of diltiazem HCl release profiles was also investigated. Generally, the presence of sodium metabisulfite stabilized the release of drug from PEO matrices stored at 40?°C for 8 weeks. Whilst the absence of metabisulfite caused an increase in drug release from polyox matrices when stored at 40?°C. The results indicate that all three concentrations (0.25, 0.5 and 1% w/w) of sodium metabisulfite were able to overcome structural changes of polyox samples hence stabilizing the drug release. The results also showed that the incorporation of fillers in polyox matrices reduced the sensitivity of drug release when stored at elevated temperature. This indicates that when these excipients were used there was no need to incorporate additional antioxidant. DSC results showed that there was no difference in the melting points of fresh polyox samples and aged polyox samples containing sodium metabisulfite, whereas the melting point of aged polyox samples without sodium metabisulfite were lower than fresh polyox samples. This indicates that the presence of metabisulfite is essential to stabilize polyox samples.     

Antibiotic drug release behavior of poly (vinyl alcohol)/sodium alginate hydrogels

Poly (vinyl alcohol)/sodium alginate hydrogels were prepared by freeze-thaw followed by calcium ion crosslinking. Chloramphenicol release behavior from the poly (vinyl alcohol)/sodium alginate hydrogels in mimic conditions of gastrointestinal tract was examined. The effects of composition, number of freeze-thaw cycles and calcium ion concentration on drug release process were investigated. The results showed that the cumulative release amount of chloramphenicol from the hydrogels (crosslinked through 4 freeze-thaw cycles and immersed in 2 % calcium chloride solution) decreased from 84.3 % to 72.3 % as sodium alginate content increased from 0 % to 75 %. For the hydrogels containing 50 % sodium alginate and immersed in 2 % calcium chloride solution after the freeze-thaw cycles, cumulative release amount of chloramphenicol decreased from 83.5 % to 76.6 % as the freeze-thaw cycles increased from 2 to 6. Cumulative release amount of chloramphenicol from the hydrogels containing 50 % sodium alginate and with 4 freeze-thaw cycles decreased from 79.8 % to 75.6 % when concentration of calcium chloride solution increased from 1 % to 4 %.     

Tracking the effect of microspheres size on the drug release from a microsphere/sucrose acetate isobutyrate (SAIB) hybrid depot in vitro and in vivo

The effects of particle size of microspheres on the drug release from a microsphere/sucrose acetate isobutyrate (SAIB) hybrid depot (m-SAIB) was investigated to develop a long-term sustained release drug delivery system with low burst release both in vitro and in vivo. A model drug, risperidone, was first encapsulated into PLGA microspheres with different particle sizes using conventional emulsification and membrane emulsification methods. The m-SAIB was prepared by dispersing the risperidone-microspheres in the SAIB depot. The drug release from m-SAIB was double controlled by the drug diffusion from the microspheres into SAIB matrix and the drug diffusion from the SAIB matrix into the medium. Large microspheres (18.95?±?18.88?µm) prepared by the conventional homogenization method exhibited porous interior structure, which contributed to the increased drug diffusion rate from microspheres into SAIB matrix. Consequently, m-SAIB containing such microspheres showed rapid initial drug release (C_max?=_?110.1?±54.2?ng/ml) and subsequent slow drug release (C_s(4–54d)=?2.7?±?0.8?ng/ml) in vivo. Small microspheres (5.91?±?2.24?µm) showed dense interior structure with a decreased drug diffusion rate from microspheres into SAIB matrix. The initial drug release from the corresponding m-SAIB was significantly decreased (C_max?=_?40.9?±?13.7?ng/ml), whereas the drug release rate from 4 to 54 d was increased (C_s(4–54d)=4.1?±?1.0?ng/ml). By further decreasing the size of microspheres to 3.38?±?0.70?µm, the drug diffusion surface area was increased, which subsequently increased the drug release from the m-SAIB. These results demonstrate that drug release from the m-SAIB can be tailored by varying the size of microspheres to reduce the in vivo burst release of SAIB system alone.     

Design and characterization of calcium-free in-situ gel formulation based on sodium alginate and chitosan

The aim of this study was to prepare and evaluate calcium-free sustained release drug delivery systems, based on the in-situ gelation of oral suspensions containing chitosan, sodium alginate and Ranitidine as drug model. The combined effects of polymer concentrations and their interactions on the rheological characteristics of both gels and suspensions and, on the kinetics of drug release were evaluated by using a central composite face-centered design. Rheological analysis showed that suspensions were potentially stable, with a viscosity increased by 1000 times compared to that of water. In addition, the obtained gels were consistent; their storage modulus could reach values close to 50?kPa when alginate concentration was greater than 7.5?g/100?mL and chitosan was fixed to 0.5?g/100?mL. In these conditions gels should have a higher gastric residence time, in comparison to the standard gastric emptying time (～2?h). Evaluation of the in-vitro release kinetics of Ranitidine showed that the association of the lowest concentration of chitosan (0.5?g/100?mL) with higher alginate concentrations generates sustained release kinetics profiles. The time corresponding to 63% of release was found close to 1.5?h, in which case the process is governed by Fickian diffusion. Finally, calcium-free alginate-chitosan based on the in-situ gelation of suspensions is advantageous as a drug delivery system for sustained-release.