Development and in vitro characterization of chitosan-coated polymeric nanoparticles for oral delivery and sustained release of the immunosuppressant drug mycophenolate mofetil

Objective: To develop an oral sustained release formulation of mycophenolate mofetil (MMF) for once-daily dosing, using chitosan-coated polylactic acid (PLA) or poly(lactic-co-glycolic) acid (PLGA) nanoparticles. The role of polymer molecular weight (MW) and drug to polymer ratio in encapsulation efficiency (EE) and release from the nanoparticles was explored in vitro.

Methods: Nanoparticles were prepared by a single emulsion solvent evaporation method where MMF was encapsulated with PLGA or PLA at various polymer MW and drug: polymer ratios. Subsequently, chitosan was added to create coated cationic particles, also at several chitosan MW grades and drug: polymer ratios. All the formulations were evaluated for mean diameter and polydispersity, EE as well as in vitro drug release. Differential scanning calorimetry (DSC), surface morphology, and in vitro mucin binding of the nanoparticles were performed for further characterization.

Results: Two lead formulations comprise MMF: high MW, PLA: medium MW chitosan 1:7:7 (w/w/w), and MMF: high MW, PLGA: high MW chitosan 1:7:7 (w/w/w), which had high EE (94.34% and 75.44%, respectively) and sustained drug release over 12?h with a minimal burst phase. DSC experiments revealed an amorphous form of MMF in the nanoparticle formulations. The surface morphology of the MMF NP showed spherical nanoparticles with minimal visible porosity. The potential for mucoadhesiveness was assessed by changes in zeta potential after incubation of the nanoparticles in mucin.

Conclusion: Two chitosan-coated nanoparticles formulations of MMF had high EE and a desirable sustained drug release profile in the effort to design a once-daily dosage form for MMF.     

论三峡水库“蓄清排浑”运用方式及其优化

泥沙问题是三峡工程的关键技术问题之一,在三峡工程论证和初步设计阶段提出水库采取"蓄清排浑"的运用方式,可以解决泥沙问题。2003年水库蓄水运用以来的实践表明,水库基本遵循了"蓄清排浑"调度运用原则,并根据上游来水来沙减少等新情况对水库运用方式进行了优化调整。本文系统分析了三峡水库"蓄清排浑"运行方式及其优化调整的利弊,包括提前5年实施175 m试验性蓄水、汛期水位动态变化、汛末提前蓄水等对水库淤积和坝下游河道演变的影响,提出了进一步优化水库调度方式,形成"蓄清排浑"运用的新模式,保持水库长期使用的建议,试图为三峡水库科学高效安全运用提供科技支撑。     

采用八叉树和OSG分页结点的海量点云三维可视化

针对现有海量点云可视化方法存在索引构建时间长、内存占用大等问题，研究一种八叉树索引结合OSG分页结点的快速可视化方法，可在占用较小内存的基础上快速建立点云索引并实时调度。采用八叉树索引结构对海量点云进行数据组织，建立各层级的八叉树结点并以文件映射的方式分块保存，对结点文件重组织转换为支持OSG渲染引擎的多分辨率点云数据。采用基于OSG分页结点的实时调度技术，对海量点云进行高质量可视化。与目前两款主流的点云数据处理商业软件进行实验对比分析，结果表明所提方法具有索引建立速度快、内存占用小等优点，同时可视化交互更加流畅，适用于各种配置计算机下海量点云数据的调度管理与实时可视化。     

Self-consistent kinetic theory with nonlinear wave-particle resonances

We have developed, based on the oscillating-center transformation, a general theoretical approach for self-consistent plasma dynamics including, explicitly, effects of nonlinear(higherorder) wave-particle resonances. A specific example is then given for low-frequency responses of trapped particles in axisymmetric tokamaks. Possible applications to transport as well as nonlinear wave growth/damping are also briefly discussed.     

在轨维修后端模块接口机构的研究

在轨维修可以大大的延长空间科学仪器的使用寿命,节省大量的经济成本。为了实现空间望远镜后端模块的在轨操作和更换,设计了一套与之对应的接口机构,能够解决在轨快速定位与安装。根据321运动学定位准则,详细介绍了该接口机构的内部组成和工作原理;然后把该接口机构与后端模块进行组件级有限元仿真,仿真结果表明一阶模态远高于整机基频可以有效地避免发射时候的共振;设计了一套平面内的工装来模拟后端模块,利用等效质量法对整个机构进行重力卸载;搭建实验平台,利用激光跟踪仪来测量整个后端模块的重复定位安装精度,实验数据表明,X,Y,Z 3个方向的重复平移定位误差分别为±5.58μm,±3.24μm及±3.63μm,优于总体指标±10μm;热实验结果表明整个机构可以完全释放由于温度变化产生的形变,具有很高的热稳定性;使入射光线和靶面的相对位置持续稳定,保证了较高的成像质量。为其他空间在轨维护装置提供强有力的参考价值。     

Chitosan Microspheres as Carriers for pH‐Indicating Species in Corrosion Sensing

Chitosan microspheres containing bromocresol green, cresol red, and phenolphthalein for corrosion detection, through pH change, are synthesized in order to be used in protective coatings for aluminium alloys. Microspheres containing corrosion detection species are characterized morphologically (SEM) and physico‐chemically (FTIR, TGA). Release studies (UV–vis) are performed in corrosion‐promoting conditions (pH, NaCl), and detection studies by immersion in media associated with corrosion activity while microspheres' sensing activity is evaluated visually. Electrochemical characterization of AA2024 substrates in the presence of chitosan spheres is performed to understand material performance, and a color change is observed as a result of local pH increase in cathodic areas when corrosion takes place. These findings can be correlated with the results from release studies and seem a promising approach for corrosion sensing purposes, not only because pH increase is possible to detect due to corrosion, but also because chitosan is considered an environmentally friendly material.     

pH-sensitive self-assembling property of poly(ethyleneimine)/cinnamic acid mixture and its effect on pH-dependent release of monoolein cubic phase

Poly(ethyleneimine) (PEI)/cinnamic acid (CA) mixture was self-assembled into microsphere in aqueous phase. As the pH value increased, the self-assembly became hardly formed. As the molar ratio of the amino group of PEI to the carboxyl group of CA increased, the pH window for the formation of self-assembly became broader. The phase transition temperature of cubic phase was 58.5–67.5°C, depending on the PEI/CA content. The release of dye loaded in cubic phase containing PEI/CA increased in a first-order fashion. The release degree was higher at a lower pH value.