Pluronic F127/聚乳酸纳米粒子的药物作用

背景:国内关于纳米粒子在水及磷酸盐缓冲液中稳定性的研究报道较少。目的:考察PluronicF127/聚乳酸纳米粒子在水及磷酸盐缓冲液中的稳定性及PluronicF127/聚乳酸聚合物作为药物载体的可行性。方法:采用透析法制备PluronicF127/聚乳酸纳米粒子,通过高效液相色谱研究该纳米粒子作为药物载体包埋紫杉醇及体外释放行为,同时采用MTT法考察该聚合物的细胞毒性。结果与结论:PluronicF127/聚乳酸纳米粒子在水中的稳定性优于磷酸盐缓冲液,其次,温度对于纳米粒子的稳定性影响较大,无论是磷酸盐缓冲液还是水中,37℃条件下粒径变化均较大,因此纳米粒子在低温下稳定性较好。包埋紫杉醇的PluronicF127/聚乳酸纳米粒子的释放曲线在前20h内呈现快速释放,此后表现为缓慢释放,约有20%的紫杉醇释放出来,MTT测试结果表明PluronicF127/聚乳酸嵌段共聚物具有很好的生物相容性。综合以上结果表明,PluronicF127/聚乳酸适合用作药物载体。     

以HER2为靶点的靶向纳米级脂质微泡超声造影剂的制备及实验研究

目的 制备以HER2受体为靶点的靶向纳米级脂质微泡超声造影剂,并观察其体外寻靶能力及体外超声显像效果.方法 制备生物素化Herceptin单抗,检测其生物素化程度及生物学活性;薄膜水化-声振法制备生物素化纳米微泡,以生物素-亲和素为桥梁制备HER2为靶点的靶向纳米级脂质微泡超声造影剂,观察其对SKOV3卵巢癌细胞的体外寻靶能力及靶向结合的体外超声显像.结果 平均每分子Herceptin单抗可与16个生物素分子结合;与游离单抗相比,生物素化抗体的活性未见明显降低(P＞0.05).体外寻靶实验观察:靶向纳米微泡组SKOV3细胞表面有明显的红染纳米微泡与其牢固结合,沿细胞表面排列较规则;非靶向组SKOV3细胞表面未结合红染的纳米微泡.靶向纳米微泡体外超声显像:细胞爬片与靶向纳米微泡孵育后可明显增强超声显像效果,对照组均未见明显超声显像.结论 应用生物素-亲和素系统成功构建了以HER2为靶点的纳米级超声造影剂,与SKOV3细胞结合后有明显超声显像效果.     

普鲁兰基肿瘤靶向性纳米粒子的制备、稳定性和体外释放☆◆

背景:普鲁兰多糖以其独特的优点在纳米递药系统领域受到越来越多的关注,但是,以普鲁兰多糖为材料进行改性制备的肿瘤靶向的纳米药物载体仍有待进一步研究与开发. 目的:观察纳米粒子和载药纳米粒子的体外稳定性及所包载药物的释放特征,初步评价其作为纳米药物载体的潜力. 方法:应用透析法制备乙酰普鲁兰叶酸偶合体纳米粒子,以表阿霉素为模型药物,制备乙酰普鲁兰叶酸偶合体/表阿霉素载药纳米粒子(FPA/EPI),应用储存法考察其稳定性,应用透析袋法观测体外释放特征. 结果与结论:乙酰普鲁兰叶酸偶合体纳米粒子和FPA/EPI的粒径分别为(204.2±10.9) nm 和(273.4±11.0) nm,在蒸馏水和体积分数10%胎牛血清中表面电位均较低,乙酰普鲁兰叶酸偶合体纳米粒子在水溶液中粒径1年内未见显著改变.载药纳米粒子对所包载的药物表阿霉素进行很好地释放,pH 5.0磷酸盐缓冲液中释放速度明显高于pH 7.4;乙酰普鲁兰叶酸偶合体纳米粒子和FPA/EPI制备容易,稳定性好,初步说明了两种粒子可望成为新型肿瘤靶向药物递药系统.     

Fe_3O_4纳米粒子的细胞相容性

背景：无论是作为化疗药物载体还是作为肿瘤热疗介质,Fe3O4纳米粒子与肿瘤细胞微观结构的作用都有待于深入研究。目的：分析Fe3O4纳米粒子的细胞相容性,探讨其在骨肉瘤化疗中作为药物载体的应用和存在的问题。方法：参照GB/T16886.5-2003（医疗器械生物学评价第5部分：体外细胞毒性试验）的评价标准和要求,偶联十六烷基三甲基溴化铵、聚乙二醇、油酸钠Fe3O4纳米粒子胶体溶液,分别与大鼠原发骨肉瘤细胞和人成纤维细胞共培养的方式对其进行细胞毒性测试。结果及结论：偶联油酸钠Fe3O4纳米粒子细胞相容性良好,参照GB/T16886.5-2003标准属于安全范围。偶联十六烷基三甲基溴化铵Fe3O4纳米粒子细胞相容性差,不适宜作为化疗药物载体进入人体。偶联聚乙二醇Fe3O4纳米粒子有一定的细胞相容性,作为磁靶向热化疗载体还需研究。     

Fe3O4纳米粒子的细胞相容性

背景:无论是作为化疗药物载体还是作为肿瘤热疗介质,Fe3O4纳米粒子与肿瘤细胞微观结构的作用都有待于深入研究。目的:分析Fe3O4纳米粒子的细胞相容性,探讨其在骨肉瘤化疗中作为药物载体的应用和存在的问题。方法:参照GB/T16886.5-2003(医疗器械生物学评价第5部分:体外细胞毒性试验)的评价标准和要求,偶联十六烷基三甲基溴化铵、聚乙二醇、油酸钠Fe3O4纳米粒子胶体溶液,分别与大鼠原发骨肉瘤细胞和人成纤维细胞共培养的方式对其进行细胞毒性测试。结果及结论:偶联油酸钠Fe3O4纳米粒子细胞相容性良好,参照GB/T16886.5-2003标准属于安全范围。偶联十六烷基三甲基溴化铵Fe3O4纳米粒子细胞相容性差,不适宜作为化疗药物载体进入人体。偶联聚乙二醇Fe3O4纳米粒子有一定的细胞相容性,作为磁靶向热化疗载体还需研究。     

表皮生长因子受体靶向纳米载体荷载C-erbB2反义寡脱氧核苷酸对人乳腺癌SK-BR3细胞的摄取与滞留

背景:结合肿瘤的分子靶向技术和纳米技术,制备出一种新的具有靶向作用的纳米载体,以达到对肿瘤更好靶向作用的目的.目的:制备表皮生长因了偶联牛血清白蛋白纳米载体,联合核素标记的c-erbB2反义寡脱氧核苷酸,体外观察人乳腺癌SK-BR3细胞对其摄取情况.设计、时间及地点:对比观察实验,于2006-09/2008-03在重庆医科大学生物化学和分子生物学教研窀,重庆医科大学分子医学与肿瘤研究中心,重庆医科大学放射医学教研室完成.材料:生血清白蛋白(生物技术级)由美围Amresco公司提供,表皮生长因子由英国PeproTech EC LTD提供,125Ⅰ由成都中核高通同位素股份有限公司提供.寡脱氧核苷酸由上海生工生物工程技术服务有限公司提供.方法:采用超声乳化-化学交联及羧和反应制备表皮生长因子偶联白蛋白靶向纳米载体,通过核素标记示踪技术检测表皮生长因子偶联白蛋白靶向纳米载体的相关性质.主要观察指标:测量表皮生长因子靶向纳米载体荷载c-erbB2反义寡脱氧核苷酸的载药量、包封率及释药率,人乳腺癌SK-BR3细胞对表皮生长因子靶向纳米载体的摄取率及滞留率.结果:表皮生长因子靶向纳米载体包载125Ⅰ标记的反义寡脱氧核苷酸组的摄取率及滞留率高于正义寡脱氧核苷酸组和无义寡脱氧核昔酸组.同时c-erbB2寡脱氧核苷酸使用纳米载体荷载组的摄取率及滞留率均高于未使用纳米载体组,差异有显著性意义(P<0.05).结论:125Ⅰ标记的表皮生长因子靶向纳米载体能够提高乳腺癌SK-BR3细胞对o-erbB2反义寡脱氧核苷酸的摄取和滞留,能达到更好的靶向作用.     

紫杉醇纳米粒子的制备及其应用

背景:紫杉醇临床用剂型紫素易引起过敏反应,因此研制新的紫杉醇新剂型就显得十分有意义。目的:研制紫杉醇新剂型,观察其在动物模型上治疗肿瘤的效果。方法:合成具有自主知识产权的生物可降解材料医用聚己内酯。采用溶剂替代法制备载紫杉醇纳米粒子,对其粒径、形态、紫杉醇含量、体外释放等进行测定。选用TA2系实验小鼠,建立乳腺癌动物模型,随机分为5组,分别局部注射生理盐水、紫素、低剂量、中剂量及高剂量紫杉醇纳米粒子进行治疗。结果与结论:实验制备的紫杉醇纳米粒子平均粒径约为153.54nm,包埋率为87.25%,紫杉醇含量19.06%。体外可恒定释放30d以上。2周药物治疗显示,各治疗组均不同程度上抑制了肿瘤的生长,其中紫杉醇纳米粒子中、高剂量组的抑瘤率明显高于紫素治疗组(P<0.01)。提示紫杉醇纳米粒子可缓释药物,中剂量组和高剂量组对小鼠乳腺癌的抑瘤率高于紫素组。     

肝癌靶向液态氟碳脂质微球造影剂的体外寻靶实验研究

目的 制备液态氟碳脂质微球造影剂并研究其体外基本特性,再引入抗人肝癌细胞单克隆抗体,采用生物素亲和素法,进行体外靶向结合的研究.方法 采用旋转蒸发法和高压均质法制备一种纳米液态氟碳脂质微球造影剂,观察其外观、形态、大小及分布情况,计算其浓度,并测定其粒径、电位;制备生物素的抗人肝癌细胞单克隆抗体HAb18,用HABA/Avidin试剂盒检测抗体的生物素化程度;制备NBD标记的生物素化的微球,采用生物素亲和素法研究其体外靶向作用.结果 所制备的液态氟碳脂质微球造影剂外观呈乳白色的混悬液,镜下观察,微球形态圆整,大小均一,性质稳定,平均粒径171.9 nm;采用生物素亲和素法制备的NBD标记的生物素化的微球可靶向结合到靶细胞上.结论 成功制备出稳定的纳米液态氟碳脂质微球造影剂,并引入抗人肝癌细胞单克隆抗体,通过生物素亲和素系统可将其特异结合到靶细胞上.     

叶酸-顺铂纳米药物的制备及其对人鼻咽癌细胞的靶向治疗作用

目的:制备连接叶酸分子的顺铂纳米药物,并研究该药物对人鼻咽癌细胞的体外靶向治疗作用.方法:采用化学共沉淀法制备顺铂纳米药物并通过聚乙二醇二胺连接叶酸分子合成叶酸-顺铂纳米药物(FA-MNP-CDDP)并对其进行表征.将人鼻咽癌细胞HNE-1和CNE-2与FA-MNP-CDDP体外共培养,采用普鲁士蓝染色法测定细胞摄取纳米药物的情况,采用MTT法测定纳米药物的细胞毒性.结果:合成FA-MNPCDDP纳米药物顺铂含量为(1.6 ±0.1)mg/mL,药物粒子平均直径为(10.1 ±1.5)nm.表达叶酸受体的HNE-1细胞对该纳米药物摄取能力显著强于不表达叶酸受体的CNE-2细胞.FA-MNP-CDDP对HNE-1细胞的体外抑制效果明显,IC50[(1.300±0.10)μg/mL]较单纯顺铂[(2.161±0.85)μg/mL]降低约40%.结论:叶酸-顺铂纳米药物具有针对鼻咽癌细胞的靶向载药和抑制增殖的能力.     

新型多肽聚酰胺-胺型靶向药物载体的载药性能及细胞吸收和毒性

背景:前期研究通过噬菌体展示体内筛选方法获得了一条NCI-H460非小细胞肺癌特异结合的多肽(Lung cancer targetingpe ptide,LCTP),将该多肽与修饰的聚酰胺-胺型(Polyamidoamine,PAMAM)树枝状高分子材料连接制备了纳米靶向药物载体PAMAM-Ac-FITC-LCTP,该载体在体内外对非小细胞肺癌NCI-H460具有很好的靶向性。目的:在前期研究基础上,进一步研究PAMAM-Ac-FITC-LCTP靶向载体对阿霉素的包埋、释放及其细胞吸收和毒性性能。方法:以筛选到的多肽LCTP为靶向剂,构建了PAMAM-Ac-FITC-LCTP靶向载体。采用物理包埋法将PAMAM-Ac-FITC-LCTP与阿霉素连接,通过体外透析实验观察载体对药物的缓释功能,共聚焦显微镜观察细胞对药物的吸收。以游离阿霉素作为对照,MTT法观察载体载药后对NCI-H460细胞的作用。结果与结论:PAMAM-Ac-FITC-LCTP对阿霉素的最大包埋率为7.46%。载体对药物具有明显的缓释作用,离子浓度、pH和温度对药物的释放具有影响,说明PAMAM-Ac-FITC-LCTP主要是通过静电相互作用与阿霉素结合。PAMAM-Ac-FITC-LCTP/阿霉素短时间内较单独药物更高效进入NCI-H460细胞,而复合物24h的细胞毒性与阿霉素对细胞的毒性基本一致。以上结果说明PAMAM-Ac-FITC-LCTP可能是一个肿瘤治疗和诊断中很有用的药物靶向传输载体。     

Interferon induction by and toxicity of polyriboinosinic acid [poly(rI)].polyribocytidylic acid [poly (rC)], mismatched analog poly (rI).poly[r(C12Uracil)n], and poly(rI).poly(rC) L-lysine complexed with carboxymethylcellulose.

The ability of polyriboinosionic acid [poly(rI)].polyribocytidylic acid [poly(rC)], mismatched analog poly (rI).poly[r(C12Uracil)n], and poly(rI).poly(rC) complexed with poly L-lysine and carboxymethylcellulose [poly(ICLc)] to induce interferon and the comparative toxicity of each in cats were evaluated. Each induced high levels of circulating interferon, although poly(ICLC) injected intravenously at 1 to 4 mg/kg induced up to 10 times more interferon than the other compounds. Each compound was pyrogenic and caused a transient decrease in leukocyte numbers. Poly(rI).poly(rC) and the mismatched analog caused severe diarrhea and nausea at the highest drug concentrations (1 to 4 mg/kg), but poly (ICLC) did not. Each compound also caused depression and lethargy and impaired coordination.     

Transformation details of poly(acrylonitrile) to poly(amidoxime) during the amidoximation process

During the amidoximation process, transformation details of poly(acrylonitrile) (PAN) to poly(amidoxime) (PAO) is critical for optimizing amidoximation conditions, which determine the physicochemical properties and adsorption capabilities of PAO-based materials. Although the optimization of amidoximation conditions can be reported in the literature, a detailed research on the transformation is still missing. Herein, the effect of the amidoximation conditions (i.e. temperature, time, and NH₂OH concentration) on the physicochemical properties and adsorption capabilities of PAO was studied in detail. The results showed that the extent of amidoximation reaction increased with increasing temperature, time, and NH₂OH concentration. However, a considerably high temperature (>60 °C) and a considerably long time (>3 h) could result in the degradation and decomposition of PAO''s surface topologies and functional groups, and then decrease its adsorption capability for U(vi). The optimal amidoximation condition was 3 h, 60 °C and 50 g L⁻¹ NH₂OH. At this condition, the PAO obtained presented the highest adsorption capability for U(vi) under experimental conditions. These results provide pivotal information on the transformation of PAO-based materials during the amidoximation process.

During the amidoximation process, transformation details of poly(acrylonitrile) (PAN) to poly(amidoxime) (PAO) is critical for optimizing amidoximation conditions, which determine the physicochemical properties and adsorption capabilities of PAO-based materials.     

Resistive non-volatile memories fabricated with poly(vinylidene fluoride)/poly(thiophene) blend nanosheets

Ferroelectric poly(vinylidene fluoride)/semiconductive polythiophene (P3CPenT) blend monolayers were developed at varying blend ratios using the Langmuir–Blodgett technique. The multilayered blend nanosheets show much improved surface roughness that is more applicable for electronics applications than spin-cast films. Because of the precisely controllable bottom-up construction, semiconductive P3CPenT were well dispersed into the ferroelectric PVDF matrix. Moreover, the ferroelectric matrix contains almost 100% β crystals: a polar crystal phase responsible for the ferroelectricity of PVDF. Both the good dispersion of semiconductive P3CPenT and the outstanding ferroelectricity of the PVDF matrix in the blend nanosheets guaranteed the success of ferroelectric organic non-volatile memories based on ferroelectricity-manipulated resistive switching with a fresh high ON/OFF ratio and long endurance to 30 days.

Ferroelectric poly(vinylidene fluoride)/semiconductive polythiophene blend nanosheets show good resistive non-volatile memory performance with a fresh high ON/OFF ratio and long endurance to 30 days.

Ferroelectric capacitors memorize information by the two antiparallel polarization states coded as “0” or “1”, even after removing the applied power, serving as non-volatile memory.^1,2 However, the reading out of the stored information in such memories will change the polarization state, which is known as destructive read-out. To realize non-destructive read-out and low-energy writing in such devices, conjugated polymers were introduced into a ferroelectric polymer matrix to form phase-separated blends, which contributed to novel ferroelectric resistive switches with very simple two-terminal sandwiched devices superior to the complicated transistor type electronic elements.^3,4 In the ferroelectric nonvolatile memories, the bi-stable polarization states in ferroelectric polymers such as poly(vinylidene fluoride) (PVDF) derivatives were used to manipulate the charge transfer and injection in conjugated polymers (CPs).^3–7 This manipulation results in different resistance at on-state and off-state of the devices controlled by the ferroelectric polarization directions. Consequently, non-destructive low-voltage operation was realized in which the ferroelectric PVDF provides switching functionality. The read-out operation is performed by conduction through a nearby semiconducting layer.⁵ Thereafter, the operational mechanism of ferroelectric-driven organic resistive switches was clarified by Kemerink et al.⁸ They stressed that the stray field of the polarized ferroelectric phase can modulate the charge injection from a metallic electrode into the organic semiconductor, switching the diode from injection-limited to space-charge-limited.Although the devices show promising applications, the random phase-separation morphology gives them uncertain properties.^9,10 The most important obstacle is to prepare well-dispersive PVDF–CP phase-separated blend nanofilms because a well-dispersive hybrid nanofilm is indispensable for higher information storage density. In other words, embedding semiconductor polymers into ferroelectric polymer matrixes with domain size of CPs smaller than a few tens of nanometers (e.g. 50 nm) has remained extremely challenging to date.^6,9 Phase-separated films prepared using traditional methods such as spin-coating show a much disordered surface with root-mean-square (RMS) roughness exceeding 39.97 nm.¹¹ Such a highly rough surface tends to induce large leakage current. Especially, the annealing treatment for PVDF materials to increase crystallinity and ferroelectric phase crystals also brings a significant increment to the phase-separated domain size. From another perspective, to decrease the writing and read-out operational voltages, ultrathin blend films (thinner than 100 nm) with high-content ferroelectric crystals are also necessary. However, the reported methods to prepare polymer ferroelectric ultrathin films, e.g. spin-coating are usually performed at the cost of decreasing the ferroelectric phase or requiring high energy consumption.Previous reports have proposed a versatile method to achieve highly oriented ferroelectric polymer Langmuir–Blodgett (LB) nanofilms consisting of ferroelectric poly(vinylidene fluoride) (PVDF) and tiny amphiphilic poly(N-dodecylacrylamide) (pDDA) supplying film stability at the air–water interface and transfer properties (Fig. 1a).^12,13 The LB nanofilms, with a controllable film thickness at several nanometers'' scale and a smooth film surface, can be transferred onto solid and flexible substrates irrespective of their surface wettability. The contents of ferroelectric β crystals in the as-prepared nanofilms with no post-treatment can be up to 95%, which is the best content in such thin films ever reported.^2,14 Therefore, we investigated a strongly enhanced ferroelectricity of the PVDF LB nanofilms with no electrical poling showing one of the highest ferroelectric remanent polarization values, 6.6 μC cm⁻², for nanometer-scale films, in addition to long endurance because of the high orientation of β crystals.² The PVDF–pDDA LB nanofilms benefit both from the good film-formation properties of amphiphilic pDDA and the functionality of ferroelectric PVDF. To extend their applications, the PVDF–pDDA LB nanofilms are promising for application as a platform and matrix to combine with other functional materials such as organic functional materials and inorganic nanoparticles. Similarly, it is promising for production of well-dispersive ferroelectric/semiconductive polymer blends by addition of a third composition: semiconductive polymers at the air–water interface. Moreover, we have reported that semiconductive poly(3-hexylthiophene) (P3HT) monolayers were stabilized by mixing with the amphiphilic poly(N-dodecylacrylamide) (pDDA) at the air–water interface for field-effect transistors.¹⁵Open in a separate windowFig. 1(a) Chemical structures of poly(vinylidene fluoride) (PVDF), poly[3-(5-carboxypentyl) thiophene-2,5-diyl] (P3CPenT) and poly(N-dodecylacrylamide) (pDDA), (b) surface pressure (π)–area (A) isotherms, and (c) compressibility modulus (C_s⁻¹)–surface area (A) isotherms of PVDF–P3CPenT–pDDA Langmuir films for various weight contents of P3CPenT relative to PVDF. The straight arrow in (b) indicates the line extrapolated to determine the limiting surface area.This study examines the facile preparation of blend nanosheets of ferroelectric PVDF and semiconductive polymer, by incorporating poly[3-(5-carboxypentyl) thiophene-2,5-diyl] (P3CPenT) into PVDF–pDDA Langmuir–Blodgett (LB) nanofilms. P3CPenT is a conjugated polythiophene carboxylate (Fig. 1a) that occupies superior charge transport performance resulting from a delicate balance between its solubility and solid-state film morphologies.^16,17 The blend LB nanosheets can be transferred readily and regularly from the air–water interface onto various substrates. Phase-separation morphologies were studied based on the varying P3CPenT contents. Resistive switching properties were demonstrated in a simple sandwiched device of Al/PVDF–P3CPenT–pDDA/Au at the opposite polarization direction of the PVDF matrix.The PVDF–P3CPenT–pDDA monolayers were prepared by spreading PVDF–P3CPenT mix solution and pDDA solution onto water surface in sequence at a molar ratio of 50 : 1 (see ESI^† for details). Fig. 1b shows surface pressure (π)–area (A) isotherms of PVDF–P3CPenT–pDDA Langmuir films at varying P3CPenT contents (relative to PVDF) at 20 °C: they are designated as P3CPenT 6 wt%, P3CPenT 9 wt% and P3CPenT 23 wt%. The sharply rising curves with high collapse surface pressures up to 50 mN m⁻¹ are indicative of the formation of stable and compact Langmuir blend monolayers at the air–water interface. These pressure values are much higher than those of pure PVDF (25 mN m⁻¹) or P3CPenT (15 mN m⁻¹) (Fig. S1^†). Results suggest that amphiphilic pDDA can greatly improve film stability at the air–water interface because of excellent hydrogen bonding interactions that occur among the amide groups in pDDA backbones.¹³ The compressibility modulus (or elasticity) C_s⁻¹ was calculated from isotherm data based on eqn (1) to obtain the monolayer elastic behavior.¹⁸C_s⁻¹ = −A(dπ/dA)1In the C_s⁻¹–A curves shown in Fig. 1c, each compressed Langmuir film shows a peak value of C_s⁻¹*, manifesting the formation of a critical concentrated solid state.^19–22 Table S1^† shows the limiting surface area (S_aver), collapse surface pressure (π_c), peak compressibility modulus (C_s⁻¹*), corresponding surface pressure (π*), and corresponding occupied area (A*) for the respective P3CPenT contents. The change in the limiting surface area from 0.0224 (6 wt%) to 0.0250 nm² (23 wt%) shows the successful introduction of P3CPenT into the PVDF matrix.After confirming the film formation properties, the monolayers were transferred onto hydrophobic silicon substrates regularly (Fig. S2^†). The transfer ratios for both downstrokes and upstrokes are almost unity, based on eqn (S1).^† Low surface roughness is a crucially important parameter for electronic applications. In earlier reports, lowering the root-mean-square (RMS) roughness below 30 nm is quite a challenge for the ferroelectric/semiconductive polymer blend films because of the crystalline properties of the two polymers. The AFM images (Fig. 2a–d) of the as-prepared PVDF–P3CPenT blend LB nanosheets manifest much smoother surfaces, even for the 80-layer nanosheets by an RMS value of 10.8 nm. This value is smaller than that of the reported spin-coating films.^6,11 In Fig. 2c, the nanofiber structures in the P3CPenT 23 wt% monolayer orientate at one direction as the black arrow indicates. All the nanofibers show a regular size of 7.9 nm (Fig. 2e). In contrast, such nanofiber structures do not appear in the monolayers at low contents of P3CPenT in Fig. 2a and b, which proves that the nanofiber structures originate from P3CPenT molecules. In Fig. 2d and S3,^† the interlaced nanofiber networks in the 80-layer LB blend nanosheet caused by repeated deposition of Langmuir monolayers will provide the nodal points for electric conductivity. EDX mapping images show homogeneous dispersion of P3CPenT in PVDF, which also ensured the continuous conducting path (Fig. S4^†), while the nano-domains were not clear seen. It may originate from the similar solubility of PVDF and P3CPenT in NMP, which made the unclear phase-separation structure.Open in a separate windowFig. 2AFM images of (a)–(c) PVDF–P3CPenT–pDDA blend LB monolayer at 6, 9, and 23 wt% P3CPenT, (d) an 80-layer blend LB nanosheet (P3CPenT 23 wt%), and (e) height profile of the fiber structures in (c).The blend monolayers were readily transferred onto various substrates such as rigid silicon and flexible PET substrates (Fig. 3). The uniform interference colours of the macroscopic films at each layer number are indicative of the regular layer structures and homogeneous film transfer from water surface to the substrates. The result also evidenced the controllable preparation of functional polymer blends at several nanometres'' scale for the present work, which cannot be achieved by general film preparation methods such as drop casting and spin-coating. UV-vis spectra in Fig. 4a show a broad absorbance peak near 462 nm for P3CPenT and PVDF–P3CPenT solutions in NMP. The detected absorbance peaks at 442, 428, and 415 nm at 23 wt%, 9 wt%, and 6 wt%, respectively, evidenced the successful introduction of P3CPenT into the PVDF LB nanofilms (Fig. 4b). The tunable domain size and controllable film thickness are not the only virtues of the blend nanosheets. In Fig. 5a, the FT-IR spectra of the blend nanosheets show significant peaks at 508, 840, 1276, and 1400 cm⁻¹ at each content, which are assigned for the ferroelectric β crystals (Form I).^23–25 Characteristic peaks of paraelectric α crystals (763 and 976 cm⁻¹) were not detected. The rich β phase formation was also confirmed using XRD patterns, which showed the appearance of 110/200 reflection at 20.1° (Fig. S5^†).^12,25 The PVDF–pDDA LB films were crystalline films with a crystallinity of 50%.¹² Results confirmed that the blend nanosheets contain almost 100% ferroelectric β crystal, which is consistent with the reported value for PVDF–pDDA LB nanofilms,¹² indicating that the addition of P3CPenT did not affect the crystal structures of PVDF. The result ensures that the ferroelectric matrix in the blend nanosheets can supply a stable and large polarization electric field to modulate charge transfer and accumulation. Monolayer thickness was confirmed as 2.3, 2.6, and 2.6 nm respective for 6 wt%, 9 wt%, and 23 wt% P3CPenT containing LB nanosheets by XRD spectra (Fig. S6 and Table S2^†). All the monolayers can be uniformly and repeatedly transferred to substrates to adjust the film thickness. Therefore, the film thickness of the nanosheets can be finely modulated at several nanometres'' scale.² This report is the first of the relevant literature to describe success on the preparation of blend LB nanosheets with highly ferroelectric matrix and well-dispersive semiconductive P3CPenT.Open in a separate windowFig. 3Photographs of blend LB nanosheets with 23 wt% P3CPenT at various layers on Si substrate (left) and a 30-layer blend nanosheet on flexible PET membrane (right).Open in a separate windowFig. 4UV-vis absorption spectra of (a) P3CPenT and PVDF–P3CPenT solutions in NMP and (b) the blend LB nanosheets for various weight contents of P3CPenT relative to PVDF.Open in a separate windowFig. 5FT-IR spectra of 80-layer PVDF–P3CPenT–pDDA blend nanosheets for various P3CPenT contents.Memory devices were constructed with a simple sandwiched structure: glass substrate/gold (Au)/blend LB nanofilms/aluminum (Al) (see the inset of Fig. S7 and ESI^†).^26,27 Fig. S7a^† shows typical current (I)–voltage (V) characteristics of 30-layer blend nanosheets (78 nm), which demonstrated a reversal current hysteresis with voltage sweeping between ±20 V.^9,11 The cross-sectional SEM image of the memory device is shown in Fig. S7b,^† indicating a well-defined layer structure. The current can only flow through the P3CPenT domains because of the insulation characteristic of PVDF matrix, however, no hysteresis loop was obtained for the blend LB nanosheets. This is due to the conducting path formed by the interlaced P3CPenT nanofibers even with the presence of rich ferroelectric β phase. So our device will not follow Asadi''s mechanism as introduced in the Introduction part.Local surface potential patterns were visualized using Kelvin probe microscopy to investigate the polarization state of the devices.¹² A two-step measurement was conducted (Fig. 6a). First, a positive/negative bias voltage was applied to the conductive AFM cantilever under ambient conditions, making the sample surface polarized with a square shape. Then, the KFM mode was conducted to obtain images of the polarized patterns, which is called the reading procedure. Fig. 6b and c portray the surface potential images before and after polarization. Clearly, the inverse profile of the positive and negative polarized area is seen in Fig. 6b, which indicates the LB films are ferroelectric.Open in a separate windowFig. 6(a) Schematic illustration of Kelvin probe force microscopy measurement and surface potential images (b) before polarization and (c) after polarization.To investigate whether the device is resistive switching or not, we applied a polarizing pulse for information writing with pulse width of 2.5 s and voltage of 30 V to induce polarization states of the ferroelectric matrix in a 40-layer blend nanosheet (104 nm) as shown in Fig. 7a. The pristine state refers to as-fabricated devices that have not undergone any electrical poling. The writing voltage magnitude for both ON and OFF states is set as 30 V for 2.5 s higher than its coercive voltage: 20 V (195 MV m⁻¹ × 104 nm)² of the PVDF LB nanosheet, as we previously reported, to ensure the high polarization value in the ferroelectric matrix. The read-out operation was operated at quite low voltage by detecting the current flow in the devices. The blend nanosheet after polarizing at +30 V exerts ten-fold improved current density (ON-state) in comparison with the pristine nanosheet before polarization (Fig. 7b). In contrast, the current density decreased after polarization at −30 V (OFF-state). The results verified the resistive switching characteristics and the non-volatility nature of the memory devices fabricated with the blend nanosheets. For comparison, a control experiment for pure pDDA LB nanofilms showed no ferroelectric polarization-reversal-induced resistive switching (Fig. S8^†). It is noteworthy that by combining the ferroelectric PVDF nanosheet with semiconductive polymer, the read-out voltage is optimized even to lower than 1 V. Results show that it is highly competitive over the ferroelectric capacitors without semiconductive components, which require a reading-out voltage higher than coercive voltage, about 20 V for the 100 nm-thick films.² The ON/OFF ratio values were recorded at varying reading voltages (Fig. 7c). The maximum value of the ON/OFF ratio was approximately 891 with increasing read-out voltage to 15 V, which hit one of the highest records over the previous ferroelectric polymer – thiophene-based semiconductor polymer blend memories.^3,5,11,28 This result derives from the synergetic effects of uniform dispersion of semiconductive domains and improved ferroelectricity of the PVDF matrix. The ultrathin PVDF matrix can survive at a strong electric field up to 500 MV m⁻¹ as our previous work reported, which ensured a large operation window for reading out the stored information as well as high ON/OFF ratio values. In other words, the bottom-up construction method for functional polymer blends affords us a novel platform for materials design and micro/nanostructures manipulation. At the first stage of the work design, we expected a band bending mechanism to explain the resistive switching. However, the I–V curve in Fig. S7a^† indicated Asadi''s mechanism is not applicable for our devices. The resistive switching toward ferroelectric polarization shows similar behaviour to the reported devices.²⁸ They used a symmetric device of Au–PVDF/P3HT–Au, however, the layer structure was asymmetric because they spin-coated P3HT on the patterned P(VDF–TrFE) layer. It seems that P3HT has a continuous phase through the layer, which is different from the clearly phase-separated structures.^3,4 As mentioned above, P3CPenT took a conductive path in the nanosheet sandwiched with two different electrodes, leading to no band bending formation at the interfaces. A lot of work is necessary in the future to optimize the device structure and materials combination to understand the operation mechanism in terms of structure–property relationship, e.g. using other semiconductive polymers with different solubility from PVDF. We also investigated the device cycle endurance (fatigue property) and retention properties for the blend-nanosheet-based ferroelectric nonvolatile memories (Fig. 7d). The devices show reversible switching over many cycles up to 1000 cycles in spite of a little linear decrease of ON-current and increase of OFF-current as a function of cycle numbers, which is consistent with the reported values.²⁹ The retention of current density was demonstrated with consistent current density at the ON state up to 4 days (Fig. 7d, bottom) and the OFF state up to 30 days (Fig. S9^†). A slight degradation of current density at the ON state was observed after 4 days, which might be ascribed to the interfacial charge induced depolarization of ferroelectric domains.³⁰Open in a separate windowFig. 7(a) Schematic illustration of the operation program for the ferroelectric nonvolatile memories, (b) current density (J)–voltage (V) characteristics of the blend LB nanosheets (P3CPenT 23 wt%, 40 layers) before and after polarization, (c) ON/OFF ratios at varying read voltage, and (d) (top) the device cycle endurance at ON- and OFF-states reading at 1 V and (bottom) the retention property at ON-state reading at 3 V. Dashed lines represent the linear fits at different states.In conclusion, a bottom-up construction of ferroelectric PVDF/semiconductive P3CPenT nanoblends was achieved simply by in situ mixing at the air–water interface. The PVDF matrix manifests ultrahigh ferroelectric crystal content, approaching 100% and guaranteeing the ferroelectricity necessary for the modulation of charge transfer and accumulation. Semiconductive P3CPenT components uniformly dispersed in PVDF matrix with some nanostructures such as particles and nanofibers. Ferroelectric nonvolatile memories based on the blend nanosheets were demonstrated with resistive switching properties along with the reversal of ferroelectric polarization direction. The ON/OFF ratio values and retention time are superior to most of the previously reported values, indicative of a great potential for application of such blend nanosheets to flexible electronics.     

聚对二氧杂环己烷酮的化学合成

背景:聚对二氧杂环己烷酮是脂肪族聚酯的一种,具有优异的生物降解性,独特的醚键还使其具有良好的柔韧性。目的:化学合成聚对二氧杂环己烷酮及最佳条件的探索。方法:以辛酸亚锡作为催化剂,催化对二氧环己酮单体的本体熔融开环聚合,从而合成聚对二氧杂环己烷酮均聚物。以温度、反应时间为正交条件,设计80,100,140℃三个温度,和10,20,30h三个反应时间,考察温度和反应时间对均聚物的合成效果的影响。结果与结论:以辛酸亚锡为催化剂,催化对二氧环己酮单体的本体熔融开环聚合,成功合成了聚对二氧杂环己烷酮均聚物。从合成出的聚对二氧杂环己烷酮的单体转化率的角度来说,聚合反应最优条件为:反应温度100℃,反应时间20h。     

Coupling of mitoxantrone to poly(I).poly(C) reduces absorption after intraperitoneal administration

Coupling of mitoxantrone (M), an intercalating cytostatic, to macromolecular polynucleotides may reduce side effects after direct intraperitoneal chemotherapy by interfering with systemic absorption of M. We have administered free M (30 mg/m2) or M mixed with poly(I).poly(C) (90 mg/m2) intraperitoneally to 5 patients with peritoneal carcinosis (cross-over study): peak plasma levels (HPLC assay) were 62 +/- 12 versus 28 +/- 4 ng/ml (p less than 0.0025), AUC0-24h were 583 +/- 126 versus 481 +/- 57 ng X h/ml (p less than 0.025). Coupling of M to poly(I).poly(C) seems to reduce M absorption after intraperitoneal administration.     

A poly(allylamine hydrochloride)/poly(styrene sulfonate) microcapsule-coated cotton fabric for stimulus-responsive textiles

This study reports the design of a stimulus-responsive fabric incorporating a combination of microcapsules, containing polyelectrolytes poly(allylamine hydrochloride) (PAH) and poly(styrene sulfonate) sodium salt (PSS), formed via a layer-by-layer (LBL) approach. The use of PAH and PSS ensured that the microcapsule structure was robust and pH-sensitive. SEM and TEM studies showed that the composite microcapsule (PAH/PSS)_nPAH had a spherical morphology with a hollow structure. FTIR demonstrated the presence of PAH and PSS, confirming the composition of the microcapsule shell. DSC showed that the microcapsules were thermally stable. The size of the microcapsules ranged from 4 μm to 6 μm. The hollow microcapsules can be used as a carrier for loading and releasing chemicals under different pH conditions. The release rate of Rhodamine-B from (PAH/PSS)_nPAH microcapsules was higher at pH 5.8 than that at 7.4, confirming the pH sensitivity. The hollow structure of (PAH/PSS)_nPAH microcapsules is expected to act as a carrier and medium to introduce functional chemicals into the fabric with long-lasting property and pH stimulus responsivity. Furthermore, a positively charged compound with ethylene oxide groups was added during the coating process as a crosslinker binding (PAH/PSS)₂PAH for the microcapsules with the cotton fabric more efficiently. Using this method, numerous substances, e.g., drugs, dyes, natural herbs, or perfumes, could be stored into the LBL microcapsules for a relatively long time, constantly releasing them from the coated textiles. Since LBL microcapsules were easy to combine with fabrics, this study provided a feasible approach for the preparation of functional stimulus-responsive textiles.

This study reports a stimulus-responsive fabric incorporating a combination of microcapsules, containing polyelectrolytes poly(allylamine hydrochloride) (PAH) and poly(styrene sulfonate) sodium salt (PSS), formed via a layer-by-layer (LBL) approach.     

Drug release characteristics of multi-reservoir type microspheres with poly(dl-lactide-co-glycolide) and poly(dl-lactide).

For the multi-reservoir type microspheres composed of poly(dl-lactide-co-glycolide) (PLGA) and poly(dl-lactide) (PLA), the influence of the drug-holding layer and the non-drug-holding layer on drug release profiles was studied. The microspheres with the blend of PLGA and PLA were prepared by the W/O type emulsion-solvent evaporation technique, and cisplatin was used as a model drug. The degree of water uptake and the erosion of each polymer were evaluated to clarify the mechanism of drug release for multi-reservoir type microspheres. The blending of PLA and PLGA provided two types of microspheres in terms of the drug distribution in a microsphere, depending on the ratio of the blend: the microspheres with the drug-holding layer covered by the non-drug layer and the microspheres with the drug on the outer region. The drug release in the early period was governed by the pattern of drug distribution. The drug release rate at a steady state was governed by the erosion of the drug-holding layer. The results of present study indicate that drug release from multi-reservoir type microspheres involves the following process: (a) rapid release of the drug near the surface of microspheres, (b) formation of micropores in the non-drug-holding layer by hydration and erosion, (c) degradation of the drug-holding layer, and (d) diffusion of the drug through micropores.