Dialdehyde starch nanoparticles as antitumor drug delivery system: An in vitro, in vivo, and immunohistological evaluation

Sustaining the release of therapeutic nanoparticles in a cell-, tissue-, or disease-specific manner is a potentially powerful technology. A new drug carrier-dialdehyde starch nanoparticle (DASNP) that can sustain the loading and release of 5-fluorouracil (5-Fu) antitumor drug is reported in this study. IR spectrophotometer and 1H NMR confirmed the formation of aldehyde groups, and scan electron microscope determinations showed that the dialdehyde starch nanoparticles obtained had an average diameter of 90 nm. 5-Fu, the model drug, was conjugated into nanoparticles by aldehyde groups. These 5-Fu-binding nanoparticles significantly enhanced breast cancer cell (MCF-7) inhibition in vitro compared with free 5-Fu. After subcutaneous 0 injection in the breast tumor-loaded rats, 5-Fu-DASNP exhibited remarkable tumor-inhibitory efficacy determined by measuring tumor weight in vivo. The tumor inhibition of 5-Fu-DASNP was 61%±6%, whereas that of free 5-Fu was only 42%±4%. Bcl-2/Bax immunohistochem-istry studies indicated that 5-Fu-DASNP remarkably induced tumor tissue necrosis. These results demonstrated that the DASNP prepared in this work is a potentially effective drug carrier.     

A novel o-nitrobenzyl-based photocleavable antitumor prodrug with the capability of releasing 5-fluorourail一种基于邻硝基苄基的可光致释放5-氟尿嘧啶的新型抗癌前药

An o-nitrobenzyl-based photocleavable antitumor prodrug with a terminal carboxyl group was designed and synthesized.The photolysis properties of the prodrug were investigated by means of1H NMR,HPLC,UV,and MTT methods.The results showed that the toxicity of the anticancer drug was effectively shielded before release.However,the prodrug effectively regained the antitumor capability against cancer cells by release of 5-fluorouracil when it was exposed to ultraviolet irradiation.     

Glycyrrhizic Acid-Targeted Carbon Nanotube Nanocomposites with Polyethylenimines-Mediated for Cancer Drug Delivery

In order to enhance the efficiency and specificity of anticancer drug delivery and realize intelligently controlled release,a new multi-functional nanoparticle drug carrier was synthesized.The drug carrier was prepared by functionalizing multi-walled carbon nanotubes(MWCNTs) with polyethylenimines(PEI),fluorescein isothiocyanate(FITC) and glycyrrhizic acid(GL).After detailed characterization,doxorubicin(DOX) was loaded onto the obtained MWCNT composites through π-π stacking interactions.The drug loading capacity of the GL-functionalized material was up to 92%,and the release behavior was significantly pH-sensitive.Release at pH = 5.8(typical of the tumor cell microenvironment) was much more rapid and reached a greater extent than release under normal physiological conditions(pH = 7.4).The modified MWCNTs had high biocompatibility with the liver cancer cell line SMMC-7721,but were able to induce cell death after 24 h incubation if loaded with DOX.Tests with shorter incubation time(2 h) were undertaken to investigate the selectivity of the MWCNT composites,showed that the nanocomposites could specifically target cancer cells.The above results suggest that the functionalized carbon nanotubes-based material has potential applications for targeted delivery and controlled release of anticancer drug.     

Starch Modification for Slow Release of Herbicide Encapsulated with Concentrated Starch Paste

An attempt on starch modification has been made to increase the paste concentration of potato starch for reducing the energy consumption required for the encapsulation of herbicide within starch matrix by encapsulating 2,4-D as model herbicide. The matrix behaviors were evaluated in terms of the herbicide content,capability of swelling in water,encapsulation efficiency,and the rate of herbicide released from the matrix. To increase paste concentration of starch for decreasing the energy consumption in dry process,potato starch was acidified before the encapsulation. However,the matrix prepared in such a way showed that it weakened the control to the herbicide encapsulated,which increased the rate of herbicide released from the matrix. By introducing covalent bonds among starch molecules,the problem with the control and release rate can be completely solved. Moreover,the effects of formaldehyde amount,medium pH,herbicide content,and particle size on the matrix behaviors and release rate were also investigated. The newly developed matrix shows low capability of swelling and slow release,and reduces water evaporation in dry process by about 40% during matrix preparation.     

Folate-Polyethyleneimine Grafted Polymer Multilayer Hollow Microcapsules as a Slow-Release Carrier of Doxorubicin

A novel biodegradable and biocompatible multilayer hollow microcapsules,modified by folate-conjugated polyethyleneimine(PEI),as targeted and sustained release carriers of doxorubicin(DOX),were successfully synthesized using the sequential layer-by-layer electrostatic assembly technique from the sacrificial microtemplates(CaCOj/CMC,spherical,1.7 μm) with chitosan(CS) and sodium carboxymethyl cellulose(CMC) as the polycation and polyanion polyelectrolyte.Scanning electron microscope(SEM) observation showed that the diameter of the seven assembly multilayer microparticles was about 2.0 μm with relatively regular sphere.After the microparticle cores was removed by complexation with ethylene diamine tetraacetic acid(EDTA) for calcium ions,the range of 200- 300 nm wall thickness of microcapsules was built,and it made the forming microcapsules to be stable.Thermogravimetric analysis confirms the deposition and modification total amount of polymer on the microtemplates is about33.5%.The assembly microparticles were modified by introducing PEI,and the grafting rate of folate could reach 20.0%.It was 4times that of traditional method.The high grafting rate helped to improve targeting action of microcapsules.The deposition of DOX was prominent and the encapsulation efficiency was 96.9%,and the plateaued release of loaded drug reached 78%in pH 7.4 buffer solution,and then in pH 5.7 showed significantly a slow release.     

Cupric ion release and cytotoxicity for Yuangong Cu-IUDs and the release behavior of indomethacin for medicated 220 Cu-IUD

These years Yuangong copper-bearing intrauterine devices （Cu-IUDs） have been used because of less side effects in use. The corrosion of copper is essential to the success of contraception, and the release behavior of indomethacin from medicated Cu-IUD is related to its therapeutic effect. In this study, analytical methods were established to investigate the release behavior of cupric ion of three kinds of Yuangong Cu-IUDs and indomethacin of medicated Yuangong 220 Cu-IUD. Cu-IUDs were incubated in simulated uterine solution （SUS）. The concentrations of cupric ion and indomethacin were analyzed by flame atomic absorption spectrometer （FAAS） for 60 days and UV/vis -3310 spectrophotometer for 60 days, respectively. The morphology of copper after corrosion was characterized by SEM. In addition, we detected cytotoxicity by MTT of L929 mouse fibroblasts cells caused by extracts of the three Yuangong Cu-IUDs. The release behavior of cupric ion for three kinds of Yuangong Cu-IUDs was biphasic, which consisted of the initial burst release and then slow and constant release. In vitro release experiment confirmed a biphasic release of indomethacin from Yuangong 220. The copper wire of Yuangong Cu-IUDs showed uneven corrosion. The RGR value of Yuangong 365 Cu-IUD was smaller than that of medicated Yuangong 220 Cu-IUD and RGR value of medicated Yuangong 220 Cu-IUD was smaller than that of Yuangong 300 Cu-IUD. The cupric ion release and indomethacin release showed biphasic. Indomethacin increased the cupric ion release rate and might diminish the adverse effects caused by burst release of cupric ion. The toxicity grade of these three Yuangong Cu-IUDs was 4. We should canvass the adverse events of Cu-lUDs based on practical experiments, and try our best to reduce the toxicity of Cu-lUDs.     

Characterization of cellulose acetate micropore membrane immobilized acylase I

This paper describes an innovative method for the immobilization of acylase I, which was entrapped into the CA-CTA micropore membrane. The most suitable casting solutions proportion for immobilizing the enzyme was obtained through orthogonal experiment. Properties of the enzyme membrane were investigated and compared with those of free enzyme and blank membrane. The thermal stability and pH stability of the enzyme inside the membrane were changed by immobilization. The optimum pH was found to be 6.0, which changes 1.0 unit compared with that of free acylase I. The optimum temperature was found to be about 90℃, which is higher than that of free acylase I (60℃). Experimental results showed that immobilization had effects on the kinetic parameters of acylase I.     

Novel PLGGE graft polymeric micelles for doxorubicin delivery

Novel poly{(lactic acid)-co-[(glycolic acid)-alt-(L-glutamic acid)]}-g-monomethyl poly(ethylene glycol) (PLGGE) micelles were prepared and used as carriers for anti-tumor drug delivery. Three PEGylated PLGG copolymers (PLGGE2000, PLGGE1100 and PLGGE500) were characterized by XRD, TG and DSC. The critical micelle concentrations (CMCs) of the amphiphilic copolymers were 1.04, 0.55 and 0.13 μg/mL, respectively. The TEM, AFM and DLS measurements revealed that the micelles were homogeneous spherical nanoparticles with the diameters ranged from 50 to 150 nm when THF was used as solvent in the preparation of the micelles. Interestingly, extended cylindrical micelles were obtained using CHCl 3 as solvent. The micelles could trap doxorubicin (DOX) in the core with the highest drug loading content up to 23.7%. The mean diameter of drug loaded micelles was much bigger than that of blank micelles. The in vitro drug release of the micelles was diffusion-controlled release within the first 36 h and initial burst release was not obvious. However, after 36 h, the release rate in pH 5.0 was faster than that in pH 7.4 due to the degradation. The PLGGE micelles were nontoxic to both NIH 3T3 fibroblasts and HepG2 cells. The in vitro cytotoxicity against HepG2 cells demonstrated that the drug loaded micelles exhibited high inhibition activity to cancer cells. CLSM observation of HepG2 cells showed that DOX released from the micelles could be delivered into cell cytoplasm and cell nuclei. PLGGE micelles are potential promising carriers for anti-tumor drug delivery.     

In Vitro Cytotoxicity and Protein Drug Release Properties of Chitosan/Heparin Mlcrospheres

Chitosan/heparin microspheres were prepared using the water-in-oil emulsification solvent evaporation technique. The microsphere diameters were controlled by selecting the fabrication process parameters. Scanning electron micrographs showed that the chitosan/heparin microspheres were regular and the surface morphology was smooth. Fourier transform infrared showed that the chitosan amino groups reacted with heparin carboxylic groups to form acylamides in the microspheres. Analysis of the microsphere cytotoxicity showed that they had no cytotoxic effect and behaved very similar to the negative control （polystyrene）. To analyze the protein drug release profiles of the microspheres, bovine serum albumin was loaded as a model drug into the microspheres and released in vitro. Marked retardation was observed in the BSA release profiles. The results show that chitosan/heparin microspheres may provide a useful controlled release protein drug system for used in pharmaceutics.     

Synthesis and evaluation of methionine and folate co-decorated chitosan self-assembly polymeric micelles as a potential hydrophobic drug-delivery system

In this study, an amphiphilic copolymer folate-succinyl-methionine-chitosan-octyl (FSMCO) was successfully synthesized step by step for self-assembling polymeric micelles. The copolymers formed micelle-like nanoparticles by their amphiphilic characteristics and structures were examined by UV-Vis absorption and Fourier transform spectroscopy. The sizes of blank and ICG derivativeloaded micelles measured by dynamic light scattering were about 170 and 140 nm, respectively, which were spherical in shape with an average zeta potential of 10 mV. Further studies on the stability showed that the micellar solutions maintain their sizes at room temperature for 1 month without distinct aggregation or dissociation. ICG derivative was much better photostable after being entrapped by the new carrier. The prepared FSMCO micelles displayed a good drug loading content (11.7%), entrapment efficiency (66.5%) and sustained release rate for the model drug fluorescein. The copolymers demonstrated weeny cytotoxicity toward Bel-7402, L02 and A549 cells when incubated for 2 d. Ligands modified micelles endowed preferable cell targeting capability and beautiful cell inhibition of HCPT-FSMCO on Bel-7402 tumor cells. This kind of polymeric micelles may be a promising nanovehicle in delivering near-infrared dyes for tumors imaging and chemotherapeutic drugs for cancer therapeutics.     

Preparation of folateconjugated starch nanoparticles and its application to tumor-targeted drug delivery vector

The lower toxicity and high effect of drug are very important for clinic therapy. So more and more atten-tion has been paid to the targeted drug delivery system. Folate receptor (FR) has been reported to be vastly overexpressed in most human tumors but se…     

可降解纳米氧化钇空心球载药体系的体外抗肿瘤效应

纳米氧化钇空心球在生物医学领域具有广泛的应用.以酚醛树脂微球为模板,合成出了尺寸均一、分散性好的纳米Y₂O₃空心球(HYNPs).它不仅在体外表现出显著的酸性降解行为,而且负载抗肿瘤药物阿霉素(DOX)后,载药体系HYNPs-DOX也表现出明显的pH响应药物释放特点.pH为5.0时,72 h的药物释放可达到70.46%;而pH为 7.4时,72 h的药物释放仅25.04%.进一步通过激光共聚焦显微镜监测载药体系在细胞内的DOX释放,发现随着时间的延长,细胞内DOX的荧光逐渐增加,表明DOX在细胞内释放量的增加.体外抗肿瘤细胞毒性结果显示,HYNPs对肿瘤细胞MCF-7和MDA-MB-231的活性没有影响,而HYNPs-DOX则表现出较高的体外抗肿瘤效应,与游离DOX相当.可见,该材料作为抗肿瘤药物载体具有潜在的应用价值.     

CMCT-FA修饰阿霉素纳米脂质体的制备与体外pH敏感释放

利用1-乙基-3-(3-二甲基丙基)-碳二亚胺(EDC)介导反应合成了叶酸偶联的羧甲基壳聚糖(CMCT-FA),以阿霉素为模型药物,采用薄膜分散-pH梯度法制备CMCT-FA修饰的阿霉素纳米脂质体。考察了CMCT-FA修饰阿霉素纳米脂质体的包封率、粒径、ζ电位以及在不同pH释药介质中的释放特性。结果表明:CMCT-FA修饰阿霉素纳米脂质体的ζ电位较未修饰脂质体明显减小,但较CMCT修饰阿霉素纳米脂质体无明显差别;与阿霉素纳米脂质体和CMCT修饰的阿霉素纳米脂质体相比,CMCT-FA修饰的阿霉素纳米脂质体在酸性条件下的药物释放速率和药物释放量均有明显提高。     

羧甲基壳聚糖修饰阿霉素纳米脂质体的制备及体外细胞实验

以羧甲基壳聚糖(CMCT)为修饰剂,采用薄膜-pH梯度法制备具有pH敏感性的阿霉素纳米脂质体(CMCT-DOX-NL),以增加抗癌药物在肿瘤部位的蓄积,同时增强抗癌药物向肿瘤细胞内的传递。结果表明:制备的CMCT-DOX-NL粒子形貌圆整,粒径分布均匀为(38±22.1)nm,药物包封率为88.83%;相比传统的阿霉素纳米脂质体(DOX-NL),CMCT-DOX-NL与Hela细胞的结合和摄取均有所提高,对细胞的杀伤作用更强;CMCT-DOX-NL的体外药物释放具有明显的pH敏感性,比普通的阿霉素脂质体更能促进阿霉素(DOX)向肿瘤细胞内的传递。     

尿素-双醛淀粉用作纺织浆料的可行性研究

介绍了尿素-双醛淀粉的制备工艺并测试了该产品的粘度、粘度热稳定性、粘附力,与玉米淀粉进行浆液性能对比,粘度热稳定性提高了6.7%,纯棉和涤棉粗纱的断裂伸长率分别提高6.9%和3.6%,结果表明尿素-双醛淀粉浆液性能优良,用作浆料来进行经纱上浆完全适宜;将尿素-双醛淀粉与变性淀粉JFJ以1∶1.98的比例混合后进行浆纱测试,测试结果与现今纺织厂常用的浆料配方相比,浆纱断裂强力、浆纱伸长率、上浆率、增强率和浆纱耐磨次数都基本相近,纱线毛羽降低率、减伸率更为优异,分别提高10.7%、4.8%,浆纱质量明显提高。     

PHBV/葡聚糖纳米药物载体的制备及表征

两亲性聚合物纳米颗粒作为疏水性抗肿瘤药物载体因其能够增强化疗效率并降低毒副作用而受到广泛关注.采用双乳液溶剂挥发法制备了聚(3-羟基丁酸酯-co-3-羟基戊酸酯)(PHBV)/葡聚糖纳米颗粒,测得平均粒径为205.0±6.9nm,Zeta电势为-1.59±0.12mV,纳米颗粒具有明显的壳核结构,粒径均一,分散性良好.将疏水性化疗药物顺铂包载后,其粒径及电势均无明显变化,载药量达19.3±2.9%.顺铂在模拟肿瘤细胞环境pH=5.5的磷酸盐缓冲液(PBS)中比正常细胞环境pH=7.4时释放更快,且累计释放周期均长达7d以上,表明该药物载体具有一定的pH响应性以及优异的缓释性能.细胞集落形成实验表明PHBV/葡聚糖纳米药物载体具有良好的生物相容性,而载药纳米颗粒对肿瘤细胞的毒性明显高于正常细胞,表明该纳米颗粒对肿瘤细胞具有更强的杀伤作用.综上所述,PHBV/葡聚糖纳米颗粒具有两亲性分子结构,合适的粒径及Zeta电势,显著的缓释效果,对肿瘤细胞具有pH响应性及更强的杀伤作用等优势,有望成为一种新型纳米药物载体,在癌症化疗中显著提高药物利用率并降低毒副作用.     

酶解双醛淀粉固定化脲酶性质的研究

采用酶解双醛淀粉固定化脲酶并对其固定化脲酶性质进行了研究。结果表明,酶解双醛淀粉固定化脲酶以后,载体之间形成较大的团状。酶解双醛淀粉载体固定化脲酶量达到24.3%。对固定化脲酶的性质研究表明,酶解双醛淀粉固定化脲酶的最适pH6.0,最适温度为70℃,具有很好的储存稳定性和较高的米氏常数,固定化脲酶重复使用10次后,活力下降了约25%。以上结果表明酶解双醛淀粉能有效固定化脲酶,是一种新型高效的固定化酶载体。     

基于单层MoS2纳米片的复合物制备及其光热性能和体外药物释放

将聚乙二醇(SH-PEG)修饰在单层MoS 2纳米片表面并进一步接枝聚乙烯亚胺(PEI),用以连接透明质酸(HA),从而构建一种新的HA-PEI-LA-MoS 2-SH-PEG纳米药物递送系统。用透射电镜、傅里叶变换红外光谱仪、紫外可见分光光度计、Zeta电位分析仪、动态光散射仪等仪器表征材料的形貌及理化性质。使用盐酸阿霉素(DOX)作为模型药物,研究复合物HA-PEI-LA-MoS 2-SH-PEG@DOX的体外药物释放行为。同时,在二硫化钼纳米复合物上负载一种新型的光热剂黑色素(Mel),研究其体外光热效果。结果表明:制备的纳米复合材料HA-PEI-LA-MoS 2-SH-PEG@(DOX/Mel)具有pH和近红外光(NIR)双重刺激响应药物释放的性能;黑色素的加载显著提高了MoS 2纳米复合物的光热效果,具有应用于肿瘤化学光热协同治疗的前景。