pH敏感水凝胶微球的制备及二甲酸钾缓释和抗菌性能分析

二甲酸钾(KDF)为抗生素的新型替代品,但在牲畜饲养中还未大量普及。采用水热法自制P型分子筛(Zeolite P),负载KDF分散在羧甲基纤维素(CMC)溶液中,与FeCl₃交联,利用凝聚法制备壳聚糖-羧甲基纤维素-P型分子筛-二甲酸钾pH敏感水凝胶抗菌微球。通过FT-IR,TGA和SEM分析可知,壳聚糖(CS)和CMC通过离子键形成结构稳定的聚电解质复合物,Zeolite P镶嵌缠绕在CMC基质中。溶胀差异性表明水凝胶微球具有高pH敏感性,可以适用不同pH条件下的持续给药。缓释动力学研究表明:抗菌微球对KDF具有一定的缓释作用,且遵循一级动力学释放模型和Higuchi模型。体外抗菌实验发现,抗菌液浓度为24 mg/mL和48 mg/mL时对大肠杆菌和金黄色葡萄球菌有显著的抗菌性,可以有效地抑制细菌的生长。     

静电喷雾法制备羧甲基纤维素/壳聚糖液芯微胶囊

以羧甲基纤维素(CMC)和壳聚糖(CS)聚合物为原料,采用静电喷雾技术制备了CMC/CS液芯微胶囊。研究了制备条件对微胶囊成型和尺寸的影响,并用激光扫描共聚焦显微镜、扫描电子显微镜和倒置显微镜进行了表征。将四环素与CMC溶液共混,以Al3+-CS作为凝固浴,在电压10 kV、液面距离20 mm、流速10 mL/h的条件下,制备了载药微胶囊。微胶囊的药物包封率随壳聚糖浓度增大而提高,在1.5%时达到99.5%。药物释放实验结果表明CMC/CS液芯微胶囊的释放率与pH有关,控释性能良好。     

可生物降解羧甲基纤维素/壳聚糖吸水保水材料的制备与表征

用溶液共混及冷冻干燥法制备了不同比例的羧甲基纤维素/壳聚糖(CMC/CS)吸水保水复合材料。用X射线衍射(XRD)、红外光谱(IR)和扫描电镜(SEM)对复合材料进行了表征,并对复合材料的吸水保水能力、吸水速率和重复使用性能进行了测试。结果表明,复合材料两组分间有很好的相容性,二者发生了一定的相互交联作用;在不同组分比例的复合材料中,当CMC/CS比例为9/1时其吸水率最高,为(6676.0±50.2)%,其吸水速度极快,且具备优异的保水性能。     

银/壳聚糖-g-甲基丙烯酸甲酯复合物的制备与抗菌性能

采用液相化学还原法合成了Ag/壳聚糖(CS)复合胶乳, 并制备了 Ag/CS-g-甲基丙烯酸甲酯(MMA)复合物。研究结果表明, 纳米Ag粒子对CS与MMA的接枝聚合起阻碍作用, 导致接枝率和接枝效率比无Ag粒子存在时有所下降。结构表征显示纳米Ag粒子均匀分散于复合物中。抗菌评价结果表明: Ag/CS和 Ag/CS-g-MMA 复合抗菌剂具有比Ag或CS单一抗菌剂更高效的抗菌性能, Ag/CS-g-MMA 复合物对E.coli、 B.subtilis、 S.aureus和P.aeruginosa四种菌的抑菌率分别为96.3%、 97.6%、 93.2%、 95.8%; Ag/CS-g-MMA复合抗菌剂的抗菌性能是纳米Ag粒子与CS协同作用的结果。      

羧甲基壳聚糖/Ce^3＋掺杂TiO2复合抗菌材料的研究

采用溶胶-凝胶法制备稀土（Ce^3＋）掺杂纳米TiO2（纳米Ce/TiO2）,借助XRD、BET、SEM对Ce/TiO2进行表征。结果表明纳米Ce/TiO2晶型为锐钛矿,平均晶粒大小为19.95nm,比表面积为43.302m^2/g。采用超声波催化法合成了羧甲基壳聚糖（CMC）,并与Ce/TiO2复配制得羧甲基壳聚糖/Ce3＋掺杂纳米TiO2复合材料（CMC/Ce/TiO2）,借助FT-IR对CMC及CMC/Ce/TiO2复合材料进行了结构表征。初步研究了纳米Ce/TiO2、普通纳米TiO2、CMC/Ce/TiO2、CMC的抗菌性能,结果显示纳米Ce/TiO2对大肠杆菌和金黄色葡萄球菌的抗菌率分别为55%和53%,普通纳米TiO2对两种菌的抗菌率分别为50%和45%,Ce^3＋的掺杂可提高纳米TiO2的抗菌性能;CMC/Ce/TiO2对大肠杆菌和金黄色葡萄球菌的抗菌率分别达到99%和95%,CMC对两种菌的抗菌率分别为90%和80%,Ce/TiO2的复合可显著提高CMC的抗菌性能。     

纳米银/壳聚糖复合材料研究进展

纳米银/壳聚糖(CS)复合材料结合了纳米银和CS的诸多优点,是一种应用前景广阔的抗菌复合材料。综述了纳米银/CS复合材料在制备方法、抗菌机理及抗菌性能、应用现状等方面的研究进展。     

静电纺丝法制备载银敷料及其性能表征

采用静电纺丝方法制备了聚乳酸(PLA)/聚己内酯(PCL)-聚乙烯醇(PVA)-壳聚糖(CS)-银(Ag)抗菌剂纳米纤维敷料。通过扫描电镜观察了纤维的微观结构,同时对其亲水性能及抗菌性进行了测试,结果表明,通过使用甲酸/丙酮作为CS的溶剂,同时添加PVA改善CS和PLA/PCL的相容性,能够获得直径均匀的纳米纤维,其静态接触角大幅度降低,吸水性、保水性和水汽透过率有显著的提高。当银抗菌剂的质量分数在0.125‰时,敷料对于革兰氏阳性菌金黄色葡萄球菌和革兰氏阴性菌大肠杆菌具有良好的抗菌活性,可用于制备创面抗菌敷料。     

壳聚糖/聚乳酸复合纳米纤维的制备及抗菌性能研究

采用静电纺丝技术制备聚乳酸(PLA)质量分数为8%的纳米纤维及壳聚糖(CS)与聚乳酸(PLA)质量比为1/5、1/10、1/15、1/20、1/40的复合纳米纤维。借助扫描电子显微镜(SEM)观察和红外光谱(FT-IR)分析,并利用振荡烧瓶法测试抗菌性能。结果表明:CS的含量对纳米纤维的形态影响很大,且PLA与CS能很好地复合;复合纳米纤维对大肠杆菌和金黄色葡萄球菌有良好的抗菌作用,当CS与PLA质量比大于1/10时,对2种菌的抑菌率达90%以上。     

具有半互穿网络结构的电场响应性水凝胶正渗透脱盐性能

为了提高凝胶驱动正渗透(FO)脱盐过程的性能,利用互穿聚合物网络技术制备一种具有半互穿网络的电场响应性水凝胶聚(2-丙烯酰胺基-2-甲基丙磺酸-co-丙烯酰胺)/羧甲基纤维素钠(P(AMPS-AM)/CMC)用作新型汲取剂。使用红外光谱和扫描电镜表征其化学结构和形貌,考察其在水中的溶胀性及在电场刺激下的响应性,并探究其在FO脱盐过程中的性能。结果表明,P(AMPS-AM)/CMC呈现孔洞结构;溶胀过程符合二级溶胀动力学模型且理论平衡溶胀度为181.5 g/g;在15 V电压刺激下具有明显的消溶胀性。在FO试验中,与未经CMC改性的P(AMPS-AM)相比,P(AMPS-AM)/CMC产生类似的初始水通量但其在15V电压刺激下的水回收率是前者的1.9倍,且连续3次再生后水回收率仅下降7.97%。此外,与已报道的水凝胶汲取剂相比,P(AMPS-AM)/CMC不仅可获得较高的水通量而且在水回收率上具有一定的优势。     

壳聚糖-银纳米粒子抗菌棉纤维灭菌机理初探

以壳聚糖(CS)为保护剂和分散剂,液相还原法制备了水溶性银纳米粒子(Chitosan/Silver Nanoparticles,CS/Ag NPs),并通过化学键负载于商业用脱脂棉表面,制得表面负载CS/Ag NPs的抗菌棉纤维。研究表明硅烷偶联剂是甲苯体积的8%,第一次处理7h,第二次处理10h,可使棉纤维的银负载量达到最大。探讨了抗菌棉纤维对耐药性甲氧西林金黄色葡萄球菌、革兰氏阳性菌金黄色葡萄球菌、蜡状芽孢杆菌和革兰氏阴性菌大肠埃希氏菌的抗菌效果。实验结果表明,对上述细菌的抑制率都大于99.8%,具有很好的抗菌效果和持久抗菌性。短接触时间内,抗菌棉纤维能够完成吸附菌体和杀灭菌体2个过程。     

Design and optimization of thermosensitive nanoemulsion hydrogel for sustained-release of praziquantel

Objective: This work aimed to develop an alternative sustained-release thermosensitive praziquantel-loaded nanoemulsion (PZQ-NE) hydrogel for better schistosomiasis treatment.

Significance: PZQ-NE-dispersed chitosan/glycerol 2-phosphate disodium/HPMC (NE/CS/β-GP/HMPC) hydrogel was successfully prepared to improve bioavailability of PZQ.

Methods: Solubility tests and pseudo-ternary phase diagrams were applied to screen optimal oils, surfactants and co-surfactants of NE. The hydrogels were characterized for gelling time, surface exudates, rheological properties and in vitro drug release. Formulation optimization of NE/CS/β-GP/HMPC hydrogel was conducted by Box–Behnken experimental design combined with response surface methodology. In vitro cytotoxicity of hydrogel was studied by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide method. The sustained-release property of PZQ in NE and optimized hydrogel was evaluated by pharmacokinetic study in rabbits.

Results: The formulation of PZQ-NE consisted of mass ratio of 12.5% capryol 90 containing PZQ (160?mg/g), 40% cremophor RH 40/tween 20 and transcutol HP (S/CoS?=?2:1), 47.5% deionized water. PZQ releasing from NE/CS/β-GP/HMPC hydrogels was best fitted to Higuchi model and governed by diffusion. Rheological investigation evidenced the themosensitive gelation of different hydrogel systems and their gel-like character at 37?°C. The optimized hydrogel formulation consisted of HPMC solution (103.69?mg/g), 3.03% (w/v) chitosan and 14.1% (w/v) β-GP showed no cytotoxicity when the addition of NE was no more than 100?mg/g. Pharmacokinetic parameters indicated that NE/CS/β-GP/HMPC hydrogel can significantly slow down drug elimination, prolong mean residence time and improve bioavailability of PZQ.

Conclusions: NE/CS/β-GP/HMPC hydrogel possessed sustained-release property and could be an alternative antischistosomal drug delivery system with improved therapeutic effect.     

Controlled release behaviors of chitosan/α, β- glycerophosphate thermo-sensitive hydrogels

Chitosan/α, β-glycerophosphate (CS/α, β-GP) thermo-sensitive hydrogels presented flowable solution state at low temperature and semisolid hydrogel when the ambient temperature increased. In this research, different concentrations of metronidazole encapsulated, CS and α, β-GP, as well as different acid solvents, were chosen to evaluate their influences on the drug release behaviors from CS/α, β-GP hydrogels. It was found that there was a sustaining release during the first 3 h followed by a plateau. SEM images showed that drugs were located both on the surface and in the interior of hydrogels. The optimal preparation conditions of this hydrogel for drug release were as follows: 1.8% (w/v) CS in HAc solvent, 5.6% (w/v) α, β-GP and 5 g/L metronidazole encapsulation. Cytotoxicity evaluation found no toxic effect. In order to control the release rate, 2.5 g/L chitosan microspheres with spherical shape and smooth surface were incorporated, and it was found that the initial release process was alleviated, while drug concentration had no obvious effect on the release rate. It could be concluded that the metronidzole release behaviors could be optimized according to practical applications.     

壳聚糖固载阳离子环糊精微球的制备及载药性能

将β-环糊精、环氧氯丙烷和氯化胆碱经一步缩聚反应制得阳离子环糊精聚合物(CPβCD),采用反相悬浮法制备壳聚糖微球(CS),再以环氧氯丙烷为交联剂制备具有CPβCD和CS双重特性的壳聚糖固载阳离子环糊精聚合物微球(CS/CPβCD),用核磁共振(1H-NMR),红外光谱(FT-IR),扫描电镜(SEM)和X射线衍射(XRD)对产物进行表征,以酮洛芬为模型药物,研究了CS/CPβCD微球的载药性能。结果表明,CS/CPβCD微球对酮洛芬的最大载药量为849.4 mg/g,吸附规律符合Freundlich等温方程,载药CS/CPβCD微球具有缓释性能,并且在模拟肠液中的缓释效果优于模拟胃液,为CS/CPβCD作为药物缓释载体提供了依据。     

Characterization and cytocompatibility of thermosensitive hydrogel embedded with chitosan nanoparticles for delivery of bone morphogenetic protein-2 plasmid DNA

A novel injectable chitosan thermosensitive hydrogel was designed as a target multi-effect scaffold for endogenous repair of the periodontium. The hydrogel complex was designed by embedding chitosan nanoparticles (CSn) loaded with bone morphogenetic protein-2 plasmid DNA (pDNA-BMP2) into a chitosan (CS)-based hydrogel with α,β-glycerophosphate (α,β-GP), termed CS/CSn(pDNA-BMP2)-GP. Characterization, the in vitro release profile for pDNA-BMP2, and cytocompatibility to human periodontal ligament cells (HPDLCs), were then conducted. The average diameter of the CSn(pDNA-BMP2) was 270.1 nm with a polydispersity index (PDI) of 0.486 and zeta potential of +27.0 mv. A DNase I protection assay showed that CSn could protect the pDNA-BMP2 from nuclease degradation. Encapsulation efficiency and loading capacity of CSn(pDNA-BMP2) were more than 80 and 30 %, respectively. The sol–gel transition time was only 3 min when CSn(pDNA-BMP2) was added into the CS/α,β-GP system. Scanning electron microscopy showed that CSn(pDNA-BMP2) was randomly dispersed in a network with regular holes and a porous structure. Weighting method showed the swelling ratio and degradation was faster in medium of pH 4.0 than pH 6.8. An in vitro pDNA-BMP2 release test showed that the cumulative release rate of pDNA-BMP2 was much slower from CS/CSn-GP than from CSn in identical release media. In release media with different pH, pDNA-BMP2 release was much slower at pH 6.8 than at pH 4.0. Three-dimensional culture with HPDLCs showed good cell proliferation and the Cell-Counting Kit-8 assay indicated improved cell growth with the addition of CSn(pDNA-BMP2) to CS/α,β-GP. In summary, the CS/CSn(pDNA-BMP2)-GP complex system exhibited excellent biological properties and cytocompatibility, indicating great potential as a gene delivery carrier and tissue regeneration scaffold for endogenous repair of the periodontium.     

Release behavior and kinetic evaluation of berberine hydrochloride from ethyl cellulose/chitosan microspheres

Novel ethyl cellulose/chitosan microspheres （ECCMs） were prepared by the method of w/o/w emulsion and solvent evaporation. The microspheres were spherical, adhesive, and aggregated loosely with a size not bigger than 5 pm. The drug loading efficiency of berberine hydrochloride （BH） loaded in microspheres were affected by chitosan （CS） concentration, EC concentration and the volume ratio of V（CS）/V（EC）. ECCMs prepared had sustained release efficiency on BH which was changed with different preparation parameters. In addition, the pH value of release media had obvious effect on the release character of ECCMs. The release rate of BH from sample B was only a little more than 30% in diluted hydrochloric acid （dHCl） and that was almost 90% in PBS during 24 h. Furthermore, the drug release data were fitted to different kinetic models to analyze the release kinetics and the mechanism from the microspheres. The released results of BH indicated that ECCMs exhibited non-Fickian diffusion mechanism in dHCI and diffusion-controlled drug release based on Fickian diffusion in PBS. So the ECCMs might be an ideal sustained release system especially in dHCl and the drug release was governed by both diffusion of the drug and dissolution of the polymeric network.     

Preparation and characterization of hybrid pH-sensitive hydrogels of chitosan-co-acrylic acid for controlled release of verapamil

In the present work crosslinked hydrogels based on chitosan (CS) and acrylic acid (AA) were prepared by free radical polymerization with various feed compositions using N,N methylenebisacrylamide (MBA) as crosslinking agent. Benzoyl peroxide was used as catalyst. Fourier transform infrared spectra (FTIR) confirmed the formation of the crosslinked hydrogels. This hydrogel is formed due to electrostatic interaction between cationic groups in CS and anionic groups in AA. Prepared hydrogels were used for dynamic and equilibrium swelling studies. For swelling behavior, effect of pH, polymeric and monomeric compositions and degree of crosslinking were investigated. Swelling studies were performed in USP phosphate buffer solutions of varying pH 1.2, 5.5, 6.5 and 7.5. Results showed that swelling increased by increasing AA contents in structure of hydrogels in solutions of higher pH values. This is due to the presence of more carboxylic groups available for ionization. On the other hand by increasing the chitosan content swelling increased in a solution of acidic pH, but this swelling was not significant and it is due to ionization of amine groups present in the structure of hydrogel. Swelling decreased with increase in crosslinking ratio owing to tighter hydrogel structure. Porosity and sol-gel fraction were also measured. With increase in CS and AA contents porosity and gel fraction increased, whereas by increasing MBA content porosity decreased and gel fraction increased. Furthermore, diffusion coefficient (D) and the network parameters i.e., the average molecular weight between crosslinks (M_c), polymer volume fraction in swollen state (V_2s), number of repeating units between crosslinks (M_r) and crosslinking density (q) were calculated using Flory-Rehner theory. Selected samples were loaded with a model drug verapamil. Release of verapamil depends on the ratios of CS/AA, degree of crosslinking and pH of the medium. The release mechanisms were studied by fitting experimental data to model equations and calculating the corresponding parameters. The result showed that the kinetics of drug release from the hydrogels in both pH 1.2 and 7.5 buffer solutions was mainly non-Fickian diffusion.     

Release profiles of theophylline from microspheres consisting of dextran derivatives and cellulose acetate butyrate: effect of polyion complex formation

The objective of this study was to evaluate the utility of mixtures among oppositely charged dextran derivatives as constituents of a controlled release microsphere. Carboxymethyldextran (CMD) and dextran sulfate (DS) were used as polyanions, and [2-(diethylamino) ethyl] dextran (EA) and [2-hydroxypropyltrimethylammonium] dextran (CDC) as polycations. The microspheres consisting of hydrophilic and hydrophobic polymers were prepared by emulsion-solvent evaporation method. The mixtures, CMD/EA, CMD/CDC, DS/EA, and DS/CDC, were used as hydrophilic polymers, because they can interact with each other to form polyion complexes for the improvement of sustained-release performances. Cellulose acetate butyrate and theophylline were used as a model hydrophobic polymer and a model drug, respectively. The yield of microspheres was excellent (more than 95%). According to observation, by scanning election microscopy (SEM) microspheres were spherical with a rough surface. The in vitro drug release from microspheres was examined in the JP XIV first fluid, pH 1.2, and second fluid, pH 6.8, at 37°C, and 100 rpm. In the DS/CDC system, drug release was depressed by formation of a polyion complex and not affected by pH of dissolution medium. The release rate was modulated by the ratio of hydrophilic and hydrophobic matrix. This particulate system, in which the polyion complex matrix is strengthened by a hydrophobic polymer, is a promising formulation for drug delivery.     

硼酸盐玻璃的原位转化及对浸泡液酸碱度的影响

采用火焰喷球法制备了组成为10Na₂O-10CaO-80B₂O₃(wt%)和19Na₂O-17CaO-64B₂O₃(wt%)的钠钙硼(NCB)玻璃(分别记为S1和S2)微球, 通过pH计、XRD、SEM、SEM-EDS、FTIR和BET研究了两种微球原位转化为中空羟基磷灰石(HA)微球及对浸泡液酸碱度的影响, 并以万古霉素为模型药物, 进一步研究了中空HA微球的缓释性能。结果表明, S1-HA微球具有较大的空腔体积和较好的药物负载性能, 其载药量和载药率分别达到13.5 mg/g和16.8%; 而S2微球对浸泡液pH的影响相对较强, S2-HA微球呈现显著的层状结构, 且具有较好的缓释性能, 其缓释时间可达到60 h。     

静电纺丝控释材料的最新研究进展

目的 综述静电纺丝的发展和原理,控释材料和控释体系,以及静电纺丝控释材料(Electrospinning controlled-release material,ECM)在药物缓释和抗菌方面的应用,旨在为ECM的相关研究提供理论参考和研究思路。方法 通过对国内外研究成果的分析和总结,介绍ECM通过环境pH调节、羧基修饰纳米纤维、光响应、纳米纤维膜厚度、纤维表面孔隙等因素进行控制释放的应用。结果 分析表明,ECM可以应用于药物缓释和抗菌方面,可以实现药物在特定条件下的响应和释放,让药物有合适的释放周期。此外,还可以对各类抗菌剂实现控释,达到长效杀菌、延长货架期的目的。结论 研究ECM(药物缓释用),能够实现药物的可控释放,保证药效的持久性,提升治疗效果。研究ECM(缓释抗菌用)可以获得更长效的抗菌效果,提高食品和药品的卫生安全性。ECM在药物缓释和抗菌方面具有很大的发展前景。