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516753274

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Abstract
Nanocomposites hydrogel (nanohydrogel) composed of chitosan (CS) and montmorillonite (MMT) were prepared and systematicallystudied for drug release behavior following electrostimulation. The deterioration of the responsiveness and reversibility of CS upon repeated on–off electrostimulation switching operations are major limitations for clinical applications, as it suffers from too much structural instability for the precise control of the release of drug upon cyclic electrostimulation. To overcome these limitations, an inorganic
phase, MMT, was incorporated in the CS matrix to enhance the anti-fatigue property and corresponding long-term stable release kinet-
ics. X-ray diffraction analysis and time-dependent optical absorbance showed that the MMT incorporated into the nanohydrogel exhib-
ited an exfoliated nanostructure. The exfoliated silica nanosheets are able to act as cross-linkers to form a network structure between the
CS and MMT, and this difference in the cross-linking density strongly affects the release of vitamin B12 under electrostimulation. With a
lower MMT concentration (1 wt.%), the release kinetics of vitamin B12 from the nanohydrogel shows a pseudo-zero-order release, and the release mechanism was changed from a diffusion-controlled mode to a swelling-controlled mode under electrostimulation. Further increasing the MMT content reduced both the diffusion exponent n and the responsiveness of the nanohydrogel to electrostimulation. In
addition, a consecutively repeated ‘‘on” and ‘‘off” operation shows that the electroresponsiveness of the nanohydrogel with higher MMT
concentrations was reduced, but its anti-fatigue behavior was considerably improved. In this work, the nanohydrogel with 2 wt.% MMT
achieved a mechanically reliable and practically desirable pulsatile release profile and excellent anti-fatigue behavior, compared with that
of the pure CS.
Keywords: Chitosan; Montmorillonite; Nanocomposite hydogel; Electrostimulation controlled release; Anti-fatigue
1. Introduction
Smart polymer hydrogels have been studied with partic-
ular emphasis on their reversible volume changes in
response to external stimuli, such as pH, solvent composi-
tion, temperature, ionic concentration and electric field [1–
3]. These hydrogels have been developed and studied with
regard to their application in several biomedical fields,
e.g. separation techniques, soft-actuators and controlled
drug delivery systems [4,5]. Of these, their use in electricallycontrolled drug delivery may offer unique advantages for
providing on-demand release of drug molecules from
implantable reservoirs. In addition, electrical control is
advantageous for coupling to sensors and microelectronics
in feedback controlled systems [6].
For electrosensitive hydrogels used as controlled drug
delivery systems, the drug release rate can be easily con-
trolled simply by modulating the electric field. Generally,
the extent of drug release increases with the magnitude of
electric field and time, but is not linearly proportional to
them [7]. Hence, it becomes more difficult to precisely con-
trol the release of drug by electrostimulation. In particular,
an important goal of drug delivery is to obtain a constant
release rate for a prolonged time. However, one problem
common to all hydrogels is that the responsiveness and
reversibility will decrease after several on–off switching
operations. For commercial applications, this fatigue prop-
erty must be improved to achieve a stable pulsatile release
under repeatedly operations. Unfortunately, few studies
have addressed this important issue, so this is one of the
research objectives of this investigation. In order to over-
come the fatigue problem of conventional hydrogels to
some extent, the incorporation of an inorganic nanophase
is an attractive alternative, i.e. production of an inorganic–
organic nanocomposite hydrogel (nanohydrogel), where
the properties of polymer matrix could be improved and
have a significant effect on the electrical deformation and
relaxation behaviors [8]. For example, Gong et al. [9]
reported that organically modified clay can enhance the
temperature response of clay–poly(N-isopropylacrylamide)
(PNIPAAm) nanocomposites. Based on hydration theory,
the organically modified clay introduces a hydrophobic
environment at the interface that can enhance the efficiency
of the thermal transition, narrow the transition range and
increase the transition rate. However, to the best of our
knowledge, little research work had been reported on the
drug release behavior of polymer–(nano)clay nanohydrogel
following electrostimulation.
Polymer–clay nanohydrogels are expected to have novel
properties because of the nanometric scale on which the
nanoclay particles, with their plate-like shape, would alter
the physical and chemical properties of the polymeric mate-
rials and improve their mechanical properties and thermal
stability [10]. Chitosan (CS), which is used as polymeric
matrix in this study, is a cationic biopolymer and has been
proposed for electrically modulated drug delivery [11].In
our previous study [12], we demonstrated that the addition
of clay to the CS matrix could strongly affect the cross-link-
ing density as well as the mechanical property, swelling–
deswelling behavior and fatigue property of the nanohy-
brids. Hence, the incorporation of negatively charged dela-
minated (exfoliated) montmorillonite (MMT) is expected
to electrostatically interact with the positively charged –
NH3+ group of CS, to generate a strong cross-linking
structure in the nanohydrogel [13] and, thus, strongly affect
the macroscopic property of the nanohydrogel and the
drug diffusion through the bulk entity. In present work,
variations in the release kinetics and the mechanism of vita-
min B12 action with respect to MMT content were investi-
gated under a given electric-field stimulus. Furthermore,
the anti-fatigue behavior with respect to the repeated field
stimuli of the resulting nanohydrogel in terms of the
MMT addition was also elucidated.

2. Materials and methods
2.1. Materials
The chitosan used in this study to prepare the CS–MMT
nanohydrogels was supplied by Aldrich–Sigma and used
without purification. The same type of chitosan was usedby Darder et al., who reported that it has an average
molecular weight of 342,500 g mol-1 and a deacetylation
degree (DD) of ca. 75% . Acetic acid and sodium phos-
phate for the preparation of buffers were purchased from
Aldrich Chemicals. Vitamin B12 (Sigma–Aldrich Co.) was
chosen as a model molecule to characterize the release
behavior from the nanohydrogel. Na+-montmorillonite,
supplied by Nanocor Co., is an Na+ form of layered smec-
tite clay with a cationic exchange capacity (CEC) of
120 meq. (100 g)-1. The MMT platelet shows a surface
dimension of about 200–500 nm in length and several tens
of nanometers in width.
2.2. Preparation of CS–MMT nanohydrogels
To prepare the CS–MMT nanohydrogels, the prepara-
tion procedure is separated into two stages. The first stage
is to prepare a suspension containing MMT and CS with a
weight ratio of 1:2 (where the CS solution was prepared by
dissolving predetermined amounts of CS in 1 wt.% acetic
acid solution and stirring for about 4 h until the CS was
completely dissolved). The CS–MMT suspensions were
obtained by adding CS to an aqueous solution containing
2 wt.% MMT (i.e. 0.5 g of Na+-MMT dispersed in 25 ml
of double-distilled water), followed by stirring at 50 C
for 24 h. To enhance the formation of exfoliation of the
MMT in the final nanohydrogel, the suspension with a
CS to MMT ratio of 2:1 was then subjected to ball-milling
for 24 h, after which the as-prepared final CS–MMT sus-
pension was used to form nanohydrogel.
In the second stage of the CS–MMT nanohydrogel
preparation, 2 wt.% CS solution was obtained by dissolv-
ing CS in 1 wt.% acetic acid solution. A small amount of
the ball-milled CS–MMT suspension was then added to
the prepared CS solution to form a CS-rich suspension,
with the MMT content controlled in the range of 1, 2, 3
and 4 wt.%, relative to the total weight of CS in the suspen-
sions, under continuous stirring at 60 C for 1 h. This final
suspension was then cast onto Petri dishes and dried at
30 C for 24 h, to form final dried nanohydrogels. The
dried nanohydrogels were then rinsed with an aqueous
solution of 1 M NaOH to remove any residual acetic acid,
followed by washing with distilled water and drying for 1
week at 40 C in vacuum until use. The compositions of
the nanohydrogels are expressed using the value of n to
define the content of MMT in CS–MMTn, where
n = CMMT, the content of the MMT incorporated in the
nanohydrogels, which ranged from 1% to 4%.

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toflyfirst

银虫 (正式写手)

摘要
由壳聚糖和蒙脱土组成的纳米复合水凝胶(纳米水凝胶)的制备药物及释放及电疗等一些列的研究。对于CS的反应能力和可逆性的恶化依赖于断开关操作电刺激的因素是临床应用的主要限制,因为它对药物释放的不精确控制导致结构不稳定性,环电刺激的精确控制。为了克服这些局限性,无机
阶段,MMT,被纳入CS矩阵,来提高抗疲劳性能和相应的长期稳定释放的动力学X射线衍射分析和随时间的光吸收表明,随MMT的加入纳米复合水凝胶显示出剥离型纳米结构。在硅薄片脱落能够作为交联剂,形成网络结构之间的这在十字联密度的强烈影响下,维生素B12电疗释放。随着MMT低浓度(1野生。%),维生素B12从纳米复合水凝胶释放动力学显示了一个假零级释放,释放机制改变,由扩散控制模式变为在电刺激下的下的膨胀控制模式。 进一步增加MMT含量会同时减少双方的扩散指数和电疗反应。
此外,连续多次的增加和减少表明了,具有较高的MMT对纳米复合水凝胶 电刺激反映浓度减少,但其抗疲劳行为大大改善。在这项工作中和纯的CS相比以纳米复合水凝胶以2%MMT取得了切实可靠的机械理想脉冲释放和优异的抗疲劳性能
关键词:壳聚糖;蒙脱石,纳米复合材料水凝胶;控释电刺激,抗疲劳
1。介绍
以足够的重视用智能高分子凝胶进行了对外部刺激的反应可逆性变化受的外界刺激因素有
如pH值,溶剂复合温度,离子浓度和电场[1 -3]。这些凝胶已经制定并研究了对于他们在几个生物医学领域的申请,
如大肠杆菌湾分离技术,软驱动器和控制药物输送系统[4,5]。其中他们在电学控制药物输送使用可为
植入式贮存提供按需药物分子释放提供独特的优势。 此外,电气控制有利于耦合传感器和微电子在反馈控制系统[6]。
为受管制药物的使用电敏感水凝胶运载系统的药物释放速率可以很容易地节能,自控只需调制电场。一般来说,在与药物释放幅度的增加幅度
电场和时间,但并不线性比例他们[7]。因此,它变得更加难以准确节能,特殊药物的电刺激释放。特别是,药物释放的一个重要目标是获得一个释放率很长一段时间常数。 然而,一个问题
共同的水凝胶的是,响应性和可逆性后一些对断开关行动而减少。对于商业应用来说,这种疲劳特性必须得到改善,实现一个在反复操作的稳定的脉冲释放。
不幸的是,少数研究处理了这一重要问题,因此这是一个这项调查研究的目标。为了克服在一定程度上的常规水凝胶的疲劳问题
一个无机纳米的纳入是一个有吸引力的研究列如有机纳米复合水凝胶生产的无机
,其中聚合物矩阵的性质和可以改进对电气变形和重大影响
松弛行为[8]。例如,gong这种方法等。 [9]报告说,有机改性粘土可提高
温度响应粘土-聚和(N -异丙基丙烯酰胺)(PNIPAAm)纳米复合材料。水化理论的基础上,有机改性粘土的引入了疏水
环境,可提高效率热传导,狭窄的范围和传导率。 然而,对我们来说很少研究工作报告了在黏土微溶胶下面的电刺激聚合物药物释放行为(纳米)。
由于纳米级上的纳米粘土粒子聚合物粘土微溶胶预计将有新的性能,将改变
聚合物的物理和化学性质,里亚尔和改善其力学性能和热稳定[10]。壳聚糖(CS),它被用于聚合物
在这项研究中矩阵,是一种阳离子生物聚合物,并已用于电调制的药物输送的提议[11条]。 在
2楼2009-11-20 17:34:38
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toflyfirst

银虫 (正式写手)

终于完了,坐不住了,尽力了

★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★
516753274(金币+50,VIP+0):不错 11-20 18:22
我们以前的研究[12],我们表明,除了粘土到CS矩阵可强烈影响的交叉连接,密度以及力学性能,肿胀行为和疲劳性能,
。因此负电荷的纳入(脱落)降低蒙脱土(MMT)的预期以静电相互作用与带正电的-氨+的CS组,产生一个强大的交叉连接结构的微气溶胶[13],因此强烈影响该胶体和宏观财产毒品扩散,通过大量的实体。 在目前的工作,在释放动力学变化以及维机制门控在一定电场刺激B12关于蒙脱土内容分钟的行动的调查。此外,反方面多次实地疲劳行为由此产生的胶体刺激的条件随MMT的加入也加以阐述。

2。材料和方法2。 1。材料在这项研究中用来编制CS的壳聚糖蒙脱土nanohydrogels是西格玛提供并且使用没有净化。壳聚糖的同类型是usedby Darder根据其报告说,平均分子量三十四点二五零万克mol每升和1乙酰度(DD)的钙。 75%醋酸钠磷酸磷酸缓冲的准备购自Aldrich化学品。维生素B12(Sigma–Aldrich有限公司)是选择作为一种模式来描述分子释放从胶体释放行为。钠MMT由Nanocor公司提供的,是钠离子的分层一届的形式蒂特粘土的阳离子交换容量(CEC)要求的120毫克当量(100克)每升。MMT血小板表面显示维约200-500微米长,几十纳米纳米的宽度。
2。 2。CS制备MMT溶胶为了准备在CS -MMT溶胶,对编制过程分为两个阶段。 第一阶段是准备含有MMT和CS重量1:2的比例(如CS溶液制备溶解在1CS的预定数额。wt%醋酸溶液和搅拌约4小时,直至CS长是完全溶解)。在CS -蒙脱土悬浮获得加入CS水溶液中含2微升蒙脱土(如0。5钠克+蒙脱土分散在25毫升双蒸馏水),其次是50搅拌均匀24小时 为加强对剥离的形成蒙脱土在最后nanohydrogel,与CS万吨的比例为2:1当时受到球磨为24小时,之后所制备的最终CS蒙脱土是用来形成nanohydrogel。在第二阶段的CS蒙脱土nanohydrogel准备2微升。CS溶液得到溶解,1 %醋酸溶液。少量的在球磨CS蒙脱土暂停然后添加到CS准备的解决方案,形成一个CS丰富的溶液,与蒙脱土含量在1,2,3范围控制和4个微升。相对于CS的总重量,在连续60℃搅拌1 h后这最后受当时到到培养皿和30度干燥24小时,以形成最终的干nanohydrogels。那个
干nanohydrogels然后与氢氧化钠溶液冲洗,以消除任何残留醋酸,其次是用蒸馏水洗涤和干燥1在40摄氏度使用一周。组成的在nanohydrogels是表示使用n的价值在CS定义蒙脱土含量MMTn,其中ñ = CMMT,在审裁处的内容纳入nanohydrogels,从1%至4%不等
3楼2009-11-20 17:59:40
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516753274

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4楼2009-11-20 18:21:45
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5楼2009-11-20 18:24:42
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