基于HPMCP包覆介孔SBA-15的pH敏感药物缓释系统

以肠溶性包衣材料羟丙甲纤维素邻苯二甲酸酯(HPMCP)为原料,在负载法莫替丁(Famo)的SBA-15药片表面包覆聚合物膜,成功制备了一种新型的pH敏感药物缓释系统, 并考察了此缓释系统在不同pH释放环境中的释放行为. 结果表明: 在模拟胃液中(SGF, pH=1.2),HPMCP能致密包覆在药片表面,从而明显延缓Famo的释放速度;而在模拟肠液中(SIF, pH=7.5),HPMCP能够迅速溶于缓释溶液中,因而对Famo释放速度的影响甚微. 因此,可以将这种新型智能药物缓释系统应用于肠道靶向给药.     

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.     

脂环族酸酐在不同极性气相色谱柱上的性能研究

研究了甲基四氢苯酐、甲基六氢苯酐、萜烯马来酸酐及氢化萜烯马来酸酐等脂族酸酐在HP-1、HP-5、OV-17和FFAP四种不同极性毛细管色谱柱上的色谱性能。分析结果表明,这四种脂环族酸酐均能在OV-17毛细管色谱柱上获得很好的峰形和分离效果。     

NIR触发的两亲性含糖聚合物修饰的纳米金棒的制备及应用

通过配体交换的方法成功将含糖聚合物PGAMA14-PCL32-SH接枝到纳米金棒的表面(Gly@AuNRs).借助X-射线光电子能谱(XPS)、动态光散射(DLS)、热重分析(TGA)等对Gly@AuNRs进行了表征.为了得到药物控释所需要的合适的实验条件,研究了近红外光照射下Gly@AuNRs在水溶液中的光热转换行为.用Gly@AuNRs包裹药物姜黄素(CUR),研究了药物的体外释放,发现近红外光能有效控制药物的体外释放.细胞实验结果表明含糖聚合物的接枝大大提高了纳米金棒的生物相容性.因此,Gly@AuNRs复合材料能够作为生物相容性载体材料,并实现近红外光触发的药物的可控释放.     

非等温DSC法研究甲壳型液晶PBPCS改性环氧树脂的固化动力学

采用非等温DSC法对聚乙烯基对苯二甲酸二(对丁氧基苯酚)酯(PBPCS)/环氧树脂/甲基四氢苯酐固化体系的固化反应热行为以及固化动力学进行了研究,分别利用Kissinger和Ozawa动力学模型计算得到各体系固化反应的表观活化能,利用Crane模型计算出固化反应级数,得出了适于该树脂体系固化反应过程的动力学方程.结果表明该体系固化反应按照一级反应进行,PBPCS的加入不改变环氧树脂的固化机理,甲壳型液晶高分子PBPCS可以用于环氧树脂的改性研究.通过固化体系的DSC分析确定了体系固化工艺为90℃/2h→120℃/2h→140℃/1.5h,为聚乙烯基对苯二甲酸二(对丁氧基苯酚)酯/环氧树脂/甲基四氢苯酐体系的固化、性能测试和应用提供了理论依据,也为甲壳型液晶高分子改性环氧树脂的研究提供一定理论基础.     

来源湛江红树内生真菌的二氢异香豆素及其抑菌活性

为了研究湛江红树(Rhizophora apiculata)植物内生真菌Fusarium sp.F67和B42的二氢异香豆素类次级代谢产物及其抑菌活性,采用色谱技术对菌株F67和B42的代谢产物进行分离纯化,确认所得化合物的结构为:3,6,8-三羟基-3,4,5,7-四甲基-3,4-二氢异香豆素(sclerotinin A)(1),二氢橘霉素(2)、5-甲基蜂蜜曲菌素(3)、5-羧基蜂蜜曲菌素(4)、4-羟基蜂蜜曲菌素(5)和蜂蜜曲菌素(6),并利用滤纸片琼脂扩散法检测化合物对7种常见致病菌的抑菌活性。在1.0 g/L质量浓度下化合物1~4对受试菌株的抑菌圈范围为5.1~11.0 mm,其中化合物4的抑菌活性相对较强,抑菌谱相对较广,可为挖掘新型抗菌药物的研究提供补充。     

光致聚合物材料中各组分对光聚合速度的影响及其在全息存储中的应用实验

本文研究了光敏剂、光引发剂、光促进剂、单体及高分子成膜树脂等成份对全息光致聚合物薄膜光存储性能的影响.在一定范围内,材料中光引发剂浓度的提高使光聚合速度显著增加,链转移剂浓度则存在一个最佳的相对浓度.适当地增加液态辅助单体含量及其所含双键官能团的数目,会明显增加光聚合速度.在聚醋酸乙烯酯薄膜中单体聚合速度明显优于在醋酸纤维素中的速度,所制备的光致聚合物材料实现了同一位置的多幅全息图像的存储和再现,表明了该材料有用于大容量全息存储的可能.     

抗癌载药体系Fe_3O_4@ZIF-8@PA的合成及药物释放

采用溶剂热法合成磁性Fe_3O_4纳米粒子,并以此为基底设计制备了一种具有pH响应核壳结构的磁性纳米复合材料Fe_3O_4@ZIF-8@PA.该材料的比饱和磁化强度可达35.46 A·m2/g,具有良好的磁性.Fe_3O_4纳米粒子呈球型结构,分散性良好.与基底相比,复合微球的粒径尺寸明显增大,但依然符合载体材料的理想尺寸且分布均匀.此外,载体具有多孔结构,表面积较大,载药效率和载药量分别高达96.4%和144.6 mg/g.在pH为7.4和5.0的条件下对载药纳米粒子进行了药物释放研究.24 h内,粒子在2种pH下累计释放量分别为39.8%和78.6%.通过药物缓释验证了载体的pH响应性能.在实验中引入了对癌细胞具有杀伤作用的植酸,使合成的载体具有一定的抗癌作用.同时采用四甲基偶氮唑盐(MTT)法对人骨肉瘤细胞(MG-63)进行了体外分析实验,证实材料与抗癌药物阿霉素(DOX)之间存在着一定的协同抗癌效果.     

聚乳酸自支持膜的叠加及其作为药物控释阻隔层的研究

发展了一种将自支持膜层层叠加制备多层膜的新方法,并研究了该薄膜对药物释放的调控效果. 首先利用聚乙烯醇作为牺牲层制备出聚乳酸自支持膜,然后将聚乳酸自支持膜转移或层层叠加到载药薄膜表面,最后对覆盖有聚乳酸薄膜的载药膜进行药物释放研究. 实验结果表明,聚乳酸薄膜对药物的释放起到了明显的调节作用,并且转移的薄膜的控释效果优于原位制备的薄膜,多层叠加的薄膜控释效果强于同等厚度的单层薄膜. 这可能是由于转移和叠加的薄膜层与层之间的空隙对药物的释放起到了缓冲作用所致. 这种基于自支持膜叠加制备多层膜的方法为药物涂层的研究提供了新思路,在生物材料、医用植入器件等领域都有一定的发展前景.     

温敏性PCL-PEG-PCL水凝胶的合成、表征及蛋白药物释放

考察了温敏性PCL-PEG-PCL水凝胶中聚乙二醇(PEG)及聚己内酯(PCL)不同嵌段组成对其溶胶-凝胶相转变温度以及亲水性药物(牛血清白蛋白, BSA)释放速率的影响. 采用开环聚合法, 以辛酸亚锡为催化剂、PEG1500/PEG1000为引发剂, 与己内酯单体发生开环共聚, 合成了一系列具有不同PEG和PCL嵌段长度的PCL-PEG-PCL型三嵌段共聚物. 通过核磁共振氢谱及凝胶渗透色谱对其组成、结构及分子量进行了表征. 共聚物的溶胶-凝胶相变温度由翻转试管法测定. 利用透射电镜、核磁共振氢谱及荧光探针技术证实了该材料在水溶液中胶束的形成. 以BSA为模型蛋白药物, 制备载药水凝胶, 利用microBCA法测定药物在释放介质中的浓度, 研究其体外释放行为. 实验结果表明, 共聚物的溶胶-凝胶相变温度与PCL及PEG嵌段长度紧密相关, 即在给定共聚物浓度情况下, 固定PEG嵌段长度而增加PCL嵌段长度, 会导致相变温度降低; 而固定PCL嵌段长度而增加PEG嵌段长度, 其相变温度相应升高. 水凝胶中蛋白药物的释放速率与疏水的PCL嵌段长度无关, 而与亲水的PEG嵌段长度密切相关, 即PEG嵌段越长, 蛋白药物释放越快.     

Thermoplastic Cellulose-Based Compound for Additive Manufacturing

The increasing environmental awareness is driving towards novel sustainable high-performance materials applicable for future manufacturing technologies like additive manufacturing (AM). Cellulose is abundantly available renewable and sustainable raw material. This work focused on studying the properties of thermoplastic cellulose-based composites and their properties using injection molding and 3D printing of granules. The aim was to maximize the cellulose content in composites. Different compounds were prepared using cellulose acetate propionate (CAP) and commercial cellulose acetate propionate with plasticizer (CP) as polymer matrices, microcellulose (mc) and novel cellulose-ester additives; cellulose octanoate (C8) and cellulose palmitate (C16). The performance of compounds was compared to a commercial poly(lactic acid)-based cellulose fiber containing composite. As a result, CP-based compounds had tensile and Charpy impact strength properties comparable to commercial reference, but lower modulus. CP-compounds showed glass transition temperature (Tg) over 58% and heat distortion temperature (HDT) 12% higher compared to reference. CAP with C16 had HDT 82.1 °C. All the compounds were 3D printable using granular printing, but CAP compounds had challenges with printed layer adhesion. This study shows the potential to tailor thermoplastic cellulose-based composite materials, although more research is needed before obtaining all-cellulose 3D printable composite material with high-performance.     

Fatty acid terminated polyanhydrides

A systematic study on the synthesis, characterization, degradation, and drug release of fatty acid terminated poly(sebacic acid) (PSA) is reported. Fatty acid terminated sebacic acid polymers were synthesized by melt condensation of acetate anhydrides of linear fatty acids (C8–C18) and sebacic anhydride oligomers to yield waxy off-white materials. Polymers with molecular weights (M_w) in the range of 9,000 and 5,000 were obtained for the 10% and 30% (weight ratio) containing fatty terminals, respectively. Up to about 30% of fatty acid terminals, the final product is mainly fatty terminated polymer with up to about 5% w/w of the symmetric fatty anhydride. Increasing amounts of fatty acid acetate anhydride in the polymerization mixture had little effect on the polymer molecular weight up to a ratio of 40 : 60 (fatty acid acetate : sebacic acid oligomer) which remains in the range of 5,000–8,000. Above this ratio the molecular weight dropped to a level of 2,000–3,000 and the percent of the symmetric anhydride increased to 10–40%. The fatty terminals had little effect on PSA melting point and crystallinity. However, the fatty terminals had a significant effect on the polymer degradation and drug release rate. PSA with 30% w/w of C14–C18 terminals degraded and released the incorporated drug for more than 4 weeks as compared with 10 days for the acetate-terminated PSA. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 3337–3344, 1999     

Continuous cellulose fiber-reinforced cellulose ester composites III. Commercial matrix and fiber options

Thermoplastic composites were prepared using two continuous regenerated cellulose fiber types, rayon and lyocell, and with several different commercially-available thermoplastic cellulose esters as matrix. Matrix options included cellulose acetate propionate (CAP), and several cellulose acetate butyrates (CAB) with different butyryl content, having different molecular weights and different methods of plasticization (adipates and very low molecular weight cellulose ester fractions). Choice of cellulose ester type was generally found to have little or no effect on mechanical properties. A significant effect, however, was revealed for fiber type. The lyocell-based composites thereby were reflective of the greater stiffness of a fiber produced from anisotropic solution state. Their modulus consistently exceeded 20GPa whereas the rayon fiber-based composites had moduli between 6 and 8GPa. The latter, however, possessed failure strains that were 3 to 4 times greater than their stiffer counterparts.     

Development and in vitro evaluation of ketoprofen extended release pellets using powder layering technique in a rotary centrifugal granulator

Powder layering technique was evaluated using laboratory scale centrifugal granulator instrument to prepare extended release pellet dosage form of ketoprofen. Ethyl cellulose and shellac polymers were used for drug layering and extended release coating in the same apparatus. Inert sugar spheres were intermittently treated with drug powder and binding solution. Combination of ethyl cellulose (45cps) and shellac was evaluated as binders at different levels (1:3 ratio, at 6%, 12%, 16% and 21%w/w polymer) for drug loading and for extended release coating (1:3 ratio at 2%, 4% and 7% w/w polymer). Pellets were evaluated for drug release study using paddle apparatus in pH 6.8 Phosphate buffer, 900ml at 100 rpm. Ethyl cellulose and shellac when used as binder during drug layering did not extend the ketoprofen release beyond 4h. However, coating of drug loaded pellets using ethyl cellulose and shellac resulted in extended release profile of ketoprofen for about 10h. Ethyl cellulose coating alone at a level of 3% w/w resulted in extended release profile. Coated pellets were evaluated for sphericity, Hardness-Friability Index and scanning electron microscopy. Scanning electron micrographs of the pellets showed a uniform coating of polymer on the core pellets substantiating the use of centrifugal granulator for extended release coating. Release pattern from the optimized batch was best explained by Higuchi's model. The drug release pattern from the pellets was found to be Non-Fickian anomalous type, involving both diffusion and erosion mechanism. Accelerated stability study of the coated pellets filled in hard gelatin capsule was conducted for 3-month period and observed for the effect on drug release profile.     

Stability and solution concentration enhancement of resveratrol by solid dispersion in cellulose derivative matrices

Resveratrol is a highly biologically active phytoalexin, found in many plant materials that are common elements of the human diet, such as grapes, nuts, and red wine. The therapeutic or disease preventative potential of this natural polyphenolic antioxidant has been limited in part due to its poor aqueous solubility and low oral bioavailability. We hypothesized that solid dispersion of resveratrol (Res) in cellulose derivative matrices might afford amorphous dispersions, from which supersaturated Res solutions would be produced in the human gastrointestinal (GI) tract, resulting in higher Res bioavailability. We carried out structure–property studies employing cellulose esters with a range of physical characteristics but possessing features suitable for use in amorphous solid dispersions: carboxymethylcellulose acetate butyrate (CMCAB), hydroxypropylmethylcellulose acetate succinate (HPMCAS) and cellulose acetate adipate propionate (CAAdP). The cellulose derivative results were compared with those of a negative control, pure crystalline Res, and a positive control, Res/poly(vinylpyrrolidinone) (PVP). Solid dispersions were characterized by powder X-ray diffraction (XRPD), modulated differential scanning calorimetry (MDSC), nuclear magnetic resonance (NMR) and Fourier transform infrared spectroscopy (FT-IR) of solid dispersions. HPMCAS and PVP solid dispersions afforded faster and more complete Res release at pH 6.8; however Res is also released from PVP matrices at pH 1.2. The carboxyl-containing cellulose derivatives release Res to only a small extent at pH 1.2. This combination of solution and solid phase stabilization against crystallization, and pH-triggered drug release makes these cellulose esters attractive candidates for Res bioavailability enhancement.     

Catalytic activity of lipase immobilized onto ultrathin films of cellulose esters

Ultrathin (approximately 2.0 nm) films of cellulose acetate (CA), cellulose acetate propionate (CAP), and cellulose acetate butyrate (CAB) supported on Si wafers have been prepared by adsorption and characterized by means of ellipsometry, atomic force microscopy (AFM), and contact angle measurements. CA, CAP, and CAB ultrathin films were characterized in air just after their formation and after annealing under reduced pressure at temperature higher than the corresponding melt temperature. Upon annealing, CA, CAP, and CAB ultrathin films became smoother and more hydrophobic, evidencing molecular reorientation at the solid-air interface. CA, CAP, and CAB films were used as supports for the immobilization of lipase. The adsorption of lipase onto annealed films was more pronounced than that onto untreated films, showing the strong affinity of lipase for the more hydrophobic substrates. Enzymatic activity was evaluated by a standard procedure, namely, (spectrophotometric) measurement of p-nitrophenol, the product formed from the hydrolysis of p-nitrophenyl dodecanoate (p-NPD). Lipase immobilized onto hydrophobic films exhibited higher activity than that of free lipase and could be recycled three times while retaining relatively high activity (loss of ca. 30% of original enzymatic activity). The effect of storing time on the activity of immobilized lipase was studied. Compared with free lipase, that immobilized onto more hydrophobic films retained 70% activity after 1 month. More importantly, the latter level of activity is similar to that of free lipase. However, lipase immobilized onto more hydrophilic films retained 50% and 30% activity after 20 and 30 days, respectively. These results are explained in terms of surface wettability and the contribution of the interactions between the polar residues of lipase and the glucopyranosyl moieties of cellulose ester to maintain the natural conformation of immobilized enzyme.     

Property Comparison of Cellulose Acetate Prepared Homogenously in Different Ionic Liquids

Cellulose acetates were synthesized homogeneously in four types of ionic liquids without any catalyst using cotton linter as the raw material and acetic anhydride as the esterification agent. FTIR, XRD and DSC were used to characterize the obtained products. It was shown that the homogeneously prepared cellulose acetates became completely amorphous. Degree of substitution of cellulose acetate synthesized in [C₄C₁Im][OAc] was found the highest; whereas T_g of this ester was the lowest. It was also found that the film made of cellulose acetate prepared in [C₄C₁Im][OAc] had lower toughness.     

Zero-order drug release cellulose acetate nanofibers prepared using coaxial electrospinning

Novel drug-loaded cellulose acetate (CA) nanofibres were prepared by a modified coaxial electrospinning process, after which their zero-order drug release profiles were determined. Using 2 % (w/v) unspinnable CA solution as a sheath fluid, coaxial electrospinning can be conducted smoothly to generate ketoprofen (KET)-loaded CA nanofibres coated with a thin layer of blank CA. Scanning electron microscopy images demonstrated that nanofibres obtained from the modified coaxial process have a smaller average diameter, a narrower size distribution, more uniform structures, and smoother surface morphologies than those generated from single-fluid electrospinning. Transmission electron microscopy observations demonstrated that the nanofibres have a thin coating layer of blank CA on their surface with a thickness of ca. 15 nm. X-ray diffraction and differential scanning calorimetry verified that KET molecules in all of the nanofibres presented an amorphous state. Fourier transform infrared spectra demonstrated that CA has good compatibility with KET, which is brought about by hydrogen bonding. In vitro dissolution tests showed that the nanofibres coated with blank CA have no initial burst release effects and can provide a zero-order drug release profile over 96 h via a diffusion mechanism. The modified coaxial electrospinning method can provide new approaches in developing cellulose-based nano products with definite structural characteristics and improved functional performance.     

Preparation and Release Behavior of Ethylcellulose Microcapsules Containing Theophylline Dispersed in Cellulose Triacetate Matrices

Using ethylcellulose and cellulose triacetate as co-wall materials, sustained release microcapsules of theophylline were prepared. The solid drug dispersed in the cellulose triacetate matrices was first prepared by solvent evaporation; then the matrices were microencapsulated by means of coacervation-phase separation of ethylcellulose from toluene solution on addition of petroleum ether. The shapes and surface characteristics of theophylline, matrices and microcapsules were examined with a scanning-electron microscope. The release of theophylline from various particles into distilled water was studied. The microcapsules had good characteristics of sustained release. The period for theophylline to dissolve from ethylcellulose microcapsules containing cellulose triacetate matrices was larger than those from only ethylcellulose microcapsules with a similar ratio of core to wall. The half-time increased with increasing content of cellulose triacetate. The release pattern which was analogous to that from only ethylcellulose microcapsules obeyed a first-order equation.     

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).