环糊精基的金属有机骨架的合成及负载5-氟尿嘧啶的研究

用溶剂热法合成了基于环糊精的金属有机骨架化合物(Na-CD-MOF),采用X-射线单晶衍射、红外光谱和元素分析进行了结构表征.以5-氟尿嘧啶(5-FU)为模型药物,研究了Na-CD-MOF的细胞毒性和载药及体外释药的能力.研究结果表明,新合成的Na-CD-MOF对5-FU的负载量最大为1.18g/g,且具有明显的缓释作用.体外细胞毒性实验表明,Na-CD-MOF具有良好的生物相容性,有望成为一种绿色的药物载体.     

乳酸-磷酸酯共聚物为载体的高分子药物的合成及其控释研究

以5-氟尿嘧啶(5-FU)为药物模型,以乳酸-磷酸酯共聚物为高分子药物载体,合成了侧链带药的乳酸-磷酸酯共聚物药物。用¹HNMR、IR、UV谱对其结构进行了表征。测定高分子药物中5-FU的含量,研究了高分子药物的体外释药性能及共聚物组成对释药性能的影响。     

ZIF-8的制备及其作为杀菌药物载体的研究

采用室温搅拌法制备了金属有机骨架材料ZIF-8.通过X射线粉末衍射(XRD)、红外光谱(IR)、N2吸附-脱附、透射电子显微镜(TEM)和扫描电子显微镜(SEM)对所得样品进行了表征分析,并以苯扎氯铵为杀菌药物模型,研究了ZIF-8对苯扎氯铵这种药物的载药及体外释药性能.表征结果显示,制备的ZIF-8是一种具有规则十二面体方钠石结构的晶体,BET比表面积为2 643m2/g.载药及体外释放实验表明,ZIF-8对浓度为4mmol/L苯扎氯铵的载药量为43g/100g ZIF-8,载药后的ZIF-8在释放90h后,释放率达84.82%,说明ZIF-8对苯扎氯铵有较好的缓释性能.     

功能化纳米粒子作为药物载体的研究

将合成的含有羧基侧基官能团的己内酯类聚合物, 用溶剂挥发与超声乳化相结合的方法制备成表面可供修饰的纳米粒子. 利用扫描电镜(SEM)研究了纳米粒子在水溶液中的形态. 使用5-氟脲嘧啶(5-FU)作为模型药物制备了载药纳米粒子, 利用紫外分光光度计法、差示扫描量热法(DSC)、X射线衍射法(XRD)研究了纳米粒子的载药及释放性能. 研究表明, 载药纳米粒子可以控制5-FU的释放速率. 释放时间可持续至96 h 以上, 符合Higuchi 动力学方程.     

羟丙基-β-环糊精磁性复合微粒的合成及作为阿霉素载体的体外释药研究

羟丙基-β-环糊精因具有内部疏水和外部亲水锥形圆筒空腔结构和良好的生物相容性在磁性药物载体方面有潜在应用价值。本研究将羟丙基-β-环糊精修饰在超顺磁性纳米四氧化三铁粒子表面制备磁性复合微粒,用红外光谱,透射电镜,振动磁强计,电感耦合等离子发射等方法对该复合微粒进行了表征,并将其用于抗肿瘤药物阿霉素的体外载药与释药实验研究。结果表明该复合微粒的粒径大小在10-20nm,饱和磁化强度59.9 emu/g,铁含量55.4%。对阿霉素的载药量为87.8 μg/mg。体外释药结果显示载药复合粒子在PBS中1天,4天,10天的累积释药量分别为35.5%, 49.3%, 76.5%,表明该载体具有一定的药物缓释功能。由此可知,羟丙基-β-环糊精磁性复合微粒可作为磁性靶向给药系统的有效载体。     

5-氟尿嘧啶分子表面印迹微球MIP-PSSS/CPVA的制备及其体外结肠定位释药特性研究

以对苯乙烯磺酸钠(SSS)为功能单体, 以N,N'-亚甲基双丙烯酰胺(MBA)为交联剂, 采用铈盐-羟基氧化还原引发体系, 在交联聚乙烯醇(CPVA)微球表面实施了5-氟尿嘧啶(5-FU)分子的表面印迹, 在微球CPVA表面形成印迹聚合物(MIP)层, 即制备了5-FU分子印迹微球MIP-PSSS/CPVA. 采用红外光谱(FTIR)和扫描电子显微镜(SEM)法, 对印迹微球进行了表征. 重点考察分析了印迹微球对5-氟尿嘧啶(5-FU)的结合(载药)性能与结合机理, 考察探索了载药微球在不同pH介质中的释放行为. 实验结果表明, 基于本体系特殊的羟基-铈盐表面引发体系, 可有效地实现5-FU分子的表面印迹, 在微球CPVA表面形成分布有大量5-FU分子印迹空穴的聚合物层. 在酸性介质中, 受强静电相互作用的驱动, 印迹微球MIP-PSSS/CPVA对5-FU分子表现出很强的结合能力, 结合容量达110 mg/g, 可实现有效载药. 载药微球的释药行为既具有强烈的pH依赖性, 又具有时滞性: 在模拟胃液中(pH＝1), 基本不释药; 在模拟小肠液中(pH＝6.8), 释药量很小; 在模拟结肠液中(pH＝7.4), 则发生突释, 表现出高效的结肠定位释放行为.     

可生物降解固体脂质纳米粒的制备、表征及药物的体外释放

以可生物降解材料硬脂酸为载体, 以葛根总黄酮为模型药物, 采用乳化蒸发-低温固化法制备固体脂质纳米粒. 采用透射电镜研究载药纳米粒形态, 激光粒度分析仪测定其粒径, X射线衍射仪进行物相鉴别, 并对纳米粒的包封率及体外释药特性等进行了研究. 分析结果表明, 所制备硬脂酸固态脂质纳米粒为类球实体, 粒径分布比较均匀, 平均粒径为(263.82±3.6) nm, 包封率为(67.53±0.12)%. X射线衍射分析证明药物以分子或细小粒子分散于脂质骨架中. 体外释药研究结果表明, 纳米粒体外释药先快后慢, 12 h累积释药50%, 包封于降解材料骨架内的药物通过骨架溶蚀缓慢释放. 药物的体外释放符合Higuchi方程.     

叶酸修饰硬脂酸接枝白芨共聚物的合成及作为抗肿瘤药物载体的研究

制备了叶酸修饰硬脂酸接枝白芨(FA-BSPs-SA)的共聚物,通过氢核磁光谱(1H NMR)、紫外-可见分光光度法(UV)及红外光谱法(IR)对其进行结构表征.以乳化-溶剂挥发法制备了载多西他赛胶束并对其进行表征,并采用噻唑蓝(MTT)法测定了共聚物及其载药胶束的细胞毒性.结果证实硬脂酸和叶酸均已接枝在白芨多糖上.疏水性药物多西他赛可被包嵌于FA-BSPs-SA的胶束内.叶酸取代度增加,胶束粒径减小,载药量与包封率均增加.载药胶束体外释药具有p H依赖性(p H=5.0~7.4).共聚物FA-BSPs-SA和BSPs-SA浓度为40μg/m L时,细胞存活率均在80%以上.与多西他赛溶液相比,相同药物浓度的FA-BSPs-SA和BSPs-SA载药胶束抗肿瘤效果更佳,且载药FA-BSPs-SA胶束对有叶酸受体表达的肿瘤细胞的抑制作用较载药BSPsSA胶束更强.FA-BSPs-SA共聚物有望作为难溶性抗肿瘤药物的纳米载体材料.     

同源细胞膜包覆智能释药纳米粒用于肝癌靶向治疗

近年来,纳米药物递送系统在癌症治疗方面的应用受到广泛关注。 传统的纳米药物递送系统存在生物相容性差、靶向性缺乏、在肿瘤部位释药缓慢等问题。 本文设计制备了一种同源细胞膜(M)包覆、癌细胞还原微环境控制释药的脂质体纳米粒子(命名为P-ss-G/D/Sf@M)来递送肝癌治疗药物索拉非尼(Sf)用于肝癌的靶向治疗。 利用薄膜水化法结合静电吸附及过膜挤压法制备包覆细胞膜的空白(P-ss-G/D@M)及载药(P-ss-G/D/Sf@M)纳米粒子。 P-ss-G/D/Sf@M对Sf的载药量为7.2%,包封率为79.9%。 体外释药结果显示,P-ss-G/D/Sf@M在还原条件下会加快药物的释放,48 h时药物释放量达到65%以上,较非还原条件下释药量提高了25%。 体外细胞实验结果证明,包覆肝癌细胞膜的纳米粒子更易被肝癌细胞摄取,表现了对肝癌细胞的靶向性,同时在肿瘤细胞高浓度谷胱甘肽(GSH)还原环境作用下,纳米粒子中的二硫键断裂,迅速释放药物,与非还原敏感载药纳米粒子相比,显著抑制肝癌细胞生长,提高细胞凋亡率。 因此,本文制备的同源细胞膜包覆的智能释药载体有可能用于今后的癌症治疗中。     

5-氟尿嘧啶/壳聚糖载药纳米微球的制备及性能

以三聚磷酸钠为交联剂,采用离子交联法制备了5-氟尿嘧啶/壳聚糖纳米微球,评价其性能、体外释药性能及对人肺癌细胞GLC-82的体外杀伤效应,并通过Zeta电位和红外光谱分析载药纳米微球形成机理.结果表明,所制备的5-Fu/CS纳米微球平均包封率为32.3%,平均载药量为25.6%,平均粒径为253nm,平均zeta电势为+8.38mV,成球性及分散性良好.CS载药纳米微球具有缓释性能,体外释药行为符合双向动力学规律.在体外作用72h,CS载药纳米微球对人肺癌细胞GLC-82的杀伤率达66.6%,杀伤效果明显优于5-Fu对照组.     

聚甘油酸-g-胆固醇胶束的制备及药物释放性能研究

以甘油酸为单体,通过本体缩聚制备了水溶性生物降解高分子聚甘油酸,利用聚甘油酸侧基上的羟基固定生物相容性好的疏水性分子胆固醇,通过亲疏水作用自组装形成胶束.以形成的胶束作为载体负载抗肿瘤药物阿霉素,研究了药物的体外释放行为.将肝癌细胞HepG2与载药胶束共培养研究其体外抗肿瘤效果.研究结果表明,聚甘油酸-g-胆固醇共聚物...     

Structure and Performance Modulation of Self-Adhesive SIS/C5 Electrospun Membranes for Transdermal Drug Delivery北大核心CSCD

Electrospun membranes are widely utilized to enhance the water vapor permeability and drug delivery performance of transdermal drug delivery patches. Due to the lack of adhesion property,however,most of them cannot closely contact with skin,which impedes the delivery of drugs to the skin,thus affecting the transdermal administration. C5 resin is used to endow poly（styrene isoprene styrene）（SIS）electrospun membranes with pressure-sensitive adhesion property. Investigation is performed on how to control the structure,adhesion properties and drug delivery performance of SIS/C5 electrospun membranes loaded with synthetic capsaicin via compositions,drugs and electrospinning conditions. The results demonstrate that the electrospun membrane with a SIS/C5 ratio of 2∶1 has excellent water vapor permeability（7. 17×10－3 g/（h·cm2）and adhesion properties（180（°）peel strength is 0. 2 kN/m,tack force is 0. 64 N/cm2 ,holding power is greater than 7 days）. The synthetic capsaicin has good compatibility with the SIS/C5 electrospun membranes,in which no drug crystallizes and the drug loading is beneficial to improve the water vapor permeability. As the drug loading is 8%,the tack force is 0. 6～0. 8 N/cm2 ,the 180（°）peel strength is 0. 2～0. 3 kN/m,the holding power is greater than 7 days,and no residue is left during peeling tests. In vitro drug release indicates that the drug has a behavior of sustained release with a 24-hour cumulative release rate of greater than 50% for all SIS/ C5 electrospun membranes,meeting the requirements of transdermal drug delivery patches. © 2022, Science Press (China). All rights reserved.     

液-液萃取-液相色谱-串联质谱法测定“地沟油”中辣椒碱类化合物及丁香酚

建立了“地沟油”中辣椒碱类化合物(包括辣椒素、二氢辣椒素、合成辣椒素)及丁香酚的液-液萃取及液相色谱-串联质谱(LC-MS/MS)检测方法。“地沟油”中辣椒碱类化合物及丁香酚用甲醇萃取,采用SUPEL COSIL ABZ+Plus dC18色谱柱(150 mm×4.6 mm, 5 μm)分离,电喷雾离子源在正、负离子模式下电离,多反应监测(MRM)模式扫描。对辣椒素、二氢辣椒素、合成辣椒素及丁香酚的检出限分别为0.02、0.03、0.03和0.6 μg/L,且在一定的质量浓度范围内线性良好。同一操作人员与不同操作人员间测定的精密度低于5%。该方法专属性强、灵敏、准确,可以作为“地沟油”的判定标准之一。     

Characterization of pore structure in metal-organic framework by small-angle X-ray scattering

MOF-5-like crystals were studied by small-angle X-ray scattering (SAXS) to reveal, both quantitatively and qualitatively, their real structural details, including pore surface characteristics, pore shape, size distribution, specific surface area (SSA), spatial distribution, and pore-network structure. A combined SAXS and wide-angle X-ray scattering (WAXS) experiment was conducted to investigate the variation of the pore structure with the MOF-5 crystalline phase produced at different cooling rates. The SSA of the MOF-5 crystals synthesized herein spanned a broad range from approximately 3100 to 800 m2/g. The real pore structures were divided into two regimes. In regime I the material consisted mainly of micropores of radius approximately 8 A as well as mesopores of radius 120 approximately 80 A. The structure in regime II was a fractal network of aggregated mesopores with radius >or=32 A as the monomer, reducing SSA and hydrogen uptake capacity at room temperature. The two regimes can be manipulated by controlling the synthesis parameters. The concurrent evolution of pore structure and crystalline phase during heating for solvent removal was also revealed by the in-situ SAXS/WAXS measurement. The understanding of the impact of the real pore structure on the properties is important to establish a favorable synthetic approach for markedly improving the hydrogen storage capacity of MOF-5.     

Characterization and in vitro release kinetics of chitosan based biocomposites from Scotch Bonnets

The main aim of this study is to formulate the combination of the bioactive composite containing chitosan/β -tricalcium phosphate (CH/β-TCP) as potential drug delivery platforms for the sustained release of antibiotics. Herein the mode of amoxicillin (AMX) maintained in the β-TCP/chitosan composite was characterized using XRD, FT-IR to confirm the phase purity and functional groups. SEM was used to examine the size and shape of particles. The SEM images of the biocomposites after drug release confirmed that they are biodegradable. In vitro drug release experiments in PBS (pH 7.4) revealed a sustained release profile in a neutral medium. Drug release profiles were evaluated according to five different kinetic models including Zero Order, First Order, Higuchi, Hixon Crowel, and Korsmeyer-Peppas. The release profile was best expressed by the Korsmeyer Peppas model because the results showed high linearity. Overall, the positive effect of chitosan coating on the drug elution profile of β-TCP as carriers for the controlled delivery of antibiotics was regarded as biocompatible for the controlled drug delivery system.     

基于聚(L-谷氨酸)树状分子的智能药物释放系统研究

以天然氨基酸L-谷氨酸为原料,通过收敛法合成了聚(L-谷氨酸)树状分子,通过半胱氨酸将抗肿瘤药物甲氨蝶呤( MTX)键合到聚(L-谷氨酸)树状分子上,构建氧化还原敏感的药物传输系统.用核磁(1H～NMR)等对载体以及载药粒子进行了表征.体外释放研究发现,载药粒子具有良好的氧化还原响应性,在不同浓度的还原剂二硫苏糖醇(D...     

氟尿嘧啶-壳寡糖/硒纳米微球的制备及抑制肿瘤细胞生长活性

为研究抗肿瘤药物与辅药负载于同一药物载体的作用效果, 首先以壳寡糖和广谱抗肿瘤药物5-氟尿嘧啶(5-Fu)为原料通过化学键合合成氟尿嘧啶-壳寡糖前体, 然后以其为模板通过溶胶-凝胶法制备了同时负载氟尿嘧啶和硒纳米颗粒的壳寡糖微球. 采用透射电子显微镜(TEM)、 Zeta电位仪和红外光谱(IR)对制备的微球进行了表征, 结果表明, 微球粒径为433 nm, 硒纳米颗粒包裹在微球内; 对微球包裹药物进行检测发现, 5-Fu装载率为(8.2±0.3)%, 硒装载率为(7.96±0.34)%; 体外缓释检测和细胞实验结果证实, 微球能够缓慢释放2种药物, 其缓释作用能很好地抑制肝癌细胞SMMC-7721的生长.     

Preparation,Characterization and Drug Release Behavior of 5-Fluorouracil Loaded Carboxylic Poly(ε-caprolactone) Nanoparticles

In this paper, 5-Fluorouracil (5-FU) loaded carboxylic poly(ε-caprolactone) nanoparticles have been prepared by emulsification/solvent evaporation o/w method, and the drug release behaviors of 5-FU were investigated. The novel carboxylic poly (ε-caprolactone) (P(CL-OPD)-mal) was synthesized via conjugation of maleic anhydride to sodium borohydride (NaBH₄) reduced poly(ε-caprolactone-co -4- carbonyl -ε-caprolactone) (P(CL-OPD)), while P(CL-OPD) was synthesized in bulk by ring-opening polymerization of ε-caprolactone and 4-carbonyl-ε-caprolactone (OPD) with stannous octoate as a catalyst. Their structures were confirmed by ¹HNMR, FT-IR and GPC. Dynamic light scattering (DLS), transmission electron microscopy (TEM), zeta potential measurements were used for nanoparticle characterization. TEM and DLS showed the nanoparticles were with spherical shape and uniform size distribution (mean diameter 70～100 nm), respectively. Zeta potential analysis revealed that the nanoparticles had an increased negative surface with the increase of carboxyl group concentration. UV spectroscopy was adopted to study the entrapment and release behaviour. The maximum 5-FU loading efficiency was 14.39% with the entrapment efficiency be 42%. In vitro release studies were performed in PBS at 37°C. Results of the study showed that the release behavior can be well-controlled, and the balanced release was up to 96 h. P(CL-OPD)-mal nanoparticles would provide increased benefit in biomedical and pharmaceutical applications.     

Tuning the hydrogen storage capacity of MOF-650 by Mg2+/Ca2+ substitution and B,N co-doped atoms: Grand canonical Monte Carlo simulation and periodic density functional theory

This study used periodic density functional theory and grand canonical Monte Carlo simulations to investigate the effects of the co-doping of B and N atoms and substituting Zn²⁺ with Mg²⁺ or Ca²⁺ in the organic linker groups of MOF-650. The functionalization increased the polarity of the organic groups, stabilizing the interaction between the MOF and hydrogen molecules. The highest average binding energy of the adsorbed hydrogen in MOF-650 NB-C7-azulene-Mg was calculated to be −4.75 to 5.40 kcal/mol for the α adsorption sites. Using the substitution of NB azulene and metal cations being Mg²⁺ or Ca²⁺, The hydrogen storage capacity of functionalized MOF-650 was increased to 22 mg/g at 90 bar/298 K, implying the modification strategy of MOF-650 would strengthen the interaction between MOF frameworks and hydrogen molecules.     

POLYCAPROLACTONE-POLY (ETHYLENE GLYCOL) BLOCK COPOLYMER Ⅲ DRUG RELEASE BEHAVIOR

The drug release behavior of degradable polymer--polycaprolactone-poly (ethyleneglycol)block copolymer(PCE) in vitro was investigated by using 5-Fluoro-uracil (5-Fu) asa model drug under a condition of pH 7. 4 at 37C. It is found that the release rate of 5-Fufrom PCE increased with increasing polyether content of the copolymer. The results showthat the increasing polyether content of the copolymer caused increasing hydrophilicity anddecreasing crystallinity of the PCE copolymer. Thus, the drug release behavior and thedegradable property of the PCE can be controlled by adjusting the composition of thecopolymer.