Mass production and size control of lipid-polymer hybrid nanoparticles through controlled microvortices

Lipid-polymer hybrid (LPH) nanoparticles can deliver a wide range of therapeutic compounds in a controlled manner. LPH nanoparticle syntheses using microfluidics improve the mixing process but are restricted by a low throughput. In this study, we present a pattern-tunable microvortex platform that allows mass production and size control of LPH nanoparticles with superior reproducibility and homogeneity. We demonstrate that by varying flow rates (i.e., Reynolds number (30-150)) we can control the nanoparticle size (30-170 nm) with high productivity (～3 g/hour) and low polydispersity (～0.1). Our approach may contribute to efficient development and optimization of a wide range of multicomponent nanoparticles for medical imaging and drug delivery.     

Lysozyme-loaded lipid-polymer hybrid nanoparticles: preparation,characterization and colloidal stability evaluation

Context: Lipid-polymer hybrid nanoparticles (LPNPs) are polymeric nanoparticles enveloped by lipid layers, which have emerged as a potent therapeutic nanocarrier alternative to liposomes and polymeric nanoparticles.

Objective: The aim of this work was to develop, characterize and evaluate LPNPs to deliver a model protein, lysozyme.

Materials and methods: Lysozyme-loaded LPNPs were prepared by using the modified w/o/w double-emulsion-solvent-evaporation method. Poly-?-caprolactone (PCL) was used as polymeric core material and tripalmitin:lechitin mixture was used to form a lipid shell around the LPNPs. LPNPs were evaluated for particle size distribution, zeta potential, morphology, encapsulation efficiency, in vitro drug release, stability and cytotoxicity.

Results: The DLS measurement results showed that the particle size of LPNPs ranged from 58.04?±?1.95?nm to 2009.00?±?0.52?nm. The AFM and TEM images of LPNPs demonstrate that LPNPs are spherical in shape. The protein-loading capacity of LPNPs ranged from 5.81% to 60.32%, depending on the formulation parameters. LPNPs displayed a biphasic drug release pattern with a burst release within 1?h, followed by sustained release afterward. Colloidal stability results of LPNPs in different media showed that particle size and zeta potential values of particles did not change significantly in all media except of FBS 100% for 120?h. Finally, the results of a cellular uptake study showed that LPNPs were significantly taken up by 83.3% in L929 cells.

Conclusion: We concluded that the LPNPs prepared with PCL as polymeric core material and tripalmitin:lechitin mixture as lipid shell should be a promising choice for protein delivery.     

Co-delivery of pemetrexed and miR-21 antisense oligonucleotide by lipid-polymer hybrid nanoparticles and effects on glioblastoma cells

Abstract

Combination therapy using anticancer drugs and nucleic acid is a more promising strategy to overcome multidrug resistance in cancer and to enhance apoptosis. In this study, lipid-polymer hybrid nanoparticles (LPNs), which contain both pemetrexed and miR-21 antisense oligonucleotide (anti-miR-21), have been developed for treatment of glioblastoma, the most aggressive type of brain tumor. Prepared LPNs have been well characterized by particle size distribution and zeta potential measurements, determination of encapsulation efficiency, and in vitro release experiments. Morphology of LPNs was determined by transmission electron microscopy. LPNs had a hydrodynamic size below 100?nm and exhibited sustained release of pemetrexed up to 10?h. Encapsulation of pemetrexed in LPNs increased cellular uptake from 6% to 78%. Results of confocal microscopy analysis have shown that co-delivery of anti-miR-21 significantly improved accumulation of LPNs in the nucleus of U87MG cells. Nevertheless, more effective cytotoxicity results could not be obtained due to low concentration of anti-miR-21, loaded in LPNs. We expect that the effective drug delivery systems can be obtained with higher concentration of anti-miR-21 for the treatment of glioblastoma.     

有源式超级电容器-蓄电池混合储能系统的研究

建立了基于功率变换器的有源式超级电容器-蓄电池混合储能系统的模型,并对控制环节进行了设计,提出了一种在脉动负载下蓄电池恒流输出的控制策略.对该模型进行了实验,并与无源式储能结构的性能进行了比较,结果表明,有源式混合储能系统配置灵活,能够大大提升系统的性能和优化蓄电池的工作过程,非常适合于负载动率脉动,尤其是瞬时功率很高,但平均功率较低的应用场合.最后,给出了确定有源式混合储能系统中超级电容器技术参数和容量配置的依据.     

Specifying concrete for chloride environments using controlled permeability formwork

The paper describes a study carried out to explore how controlled permeability formwork (CPF) can be used within existing concrete durability specifications (mix limitations) for chloride environments. Tests were carried out to consider (i) chloride diffusion rates and, under wetting and drying conditions, (ii) rates of chloride contamination build up at cover depth and (iii) reinforcement corrosion. The effects of CPF were measured against design strength, cover depth and cement type of concrete cast against ply-wood formwork (impermeable formwork—IMF). The use of CPF liner on formwork was found to significantly enhance chloride and corrosion resistance of concrete. Moreover, the results demonstrated that CPF could be used within the BS 5328 durability framework for chloride environments to allow either a 20 mm cover reduction (50 to 30 mm) at fixed design strength (40 N/mm²), or a reduction in design strength of 10 N/mm² (50 to 40 N/mm²) at fixed cover depth (30 mm). It was additionally found for Portland cement (PC) concrete that the use of CPF gave equivalent performance to concretes containing PFA and GGBS as constituents of cement and a ternary cement comprising both materials, cast against ply-wood formwork. This suggests that the ‘trade offs’ within BS 8500 for PC/PFA and PC/GGBS cements in chloride environments, could also be permitted for CPF concrete containing PC.     

A hybrid polymer gel with controlled rates of cross-link rupture and self-repair

A family of hybrid polymer gels is described, in which covalent cross-links create a permanent, stiff scaffold onto which reversible metal-ligand coordinative cross-links are added. The reversible metal-ligand interactions are shown to bear mechanical stress within the hybrid gel, and relaxations in response to that applied stress are consistent with the stress-free kinetics of ligand exchange in systems that model the reversible cross-links. The stress-induced dissociation of a model metal-ligand complex is examined by a single-molecule force spectroscopy, and its mechanical response is compared with a previously studied complex. The mechanical response of the individual interactions is relevant to those found in the family of hybrid gels, and the modular platform is therefore suitable for the study of stress-induced molecular dissociations, and their subsequent repair, within a macroscopic material of fixed structure.     

A pollution controlled hybrid interior error estimator for linear elastostatics

A hybrid error estimator using a priori interior region estimates in an a posteriori framework is presented for linear elastostatics problems in FEA. It is shown that local rates of convergence are augmented by this technique and global rates are not adversely affected. The effects of pollution for this estimator are explained and a pollution error estimator is derived using the concept of error loads. It is shown that pollution error estimation can improve the performance of both the conventional a posteriori and the hybrid techniques. A series of numerical results are presented which demonstrate the superior performance of the proposed method over previously published interior error estimation techniques. © 1998 John Wiley & Sons, Ltd.     

A functional polymeric material based on hybrid electrochemically controlled junctions

A thin film polymeric junction was fabricated which yields a molecular electronic device functionally able to learn, i.e. to respond coherently to an external training signal. The fabricated structure is based upon electrochemical control of electronic current in a conducting polymer in contact with a solid electrolyte polymer. This functional behavior bears some resemblance to simple cases of biological learning processes. We report a comprehensive electronic characterization of the device function. Additional study was performed in order to estimate the possibility of the integration of such kinds of devices in statistical adaptive networks.     

Silica-chitosan hybrid coating on Ti for controlled release of growth factors

A hybrid material composed of a silica xerogel and chitosan was coated on Ti for the delivery of growth-factors. Fibroblast growth factor (FGF) and green fluorescence protein were incorporated into the coatings for hard tissue engineering. Silica was chosen as a coating material because of its high surface area as well as its good bioactivity. Chitosan provides mechanical stability and contributes to the control of the release rate of the growth factors. When the chitosan composition was 30% or more, the hybrid coating was stable physically and mechanically. The release of the growth-factors, observed in phosphate buffer solution at 37°C, was strongly dependent on the coating material. The hybrid coating containing FGF showed significantly improved osteoblast cell responses compared to the pure xerogel coating with FGF or the hybrid coating without FGF. These results indicate that the hybrid coating is potentially very useful in enhancing the bioactivity of metallic implants by delivering growth-factors in a controlled manner.     

Multiobjective design of actively controlled structures using a hybrid optimization method

A multiobjective approach to the combined structure and control optimization problem for flexible space structures is presented. The proposed formulation addresses robustness considerations for controller design, as well as a simultaneous determination of optimum actuator locations. The structural weight, controlled system energy, stability robustness index and damping augmentation provided by the active controller are considered as objective functions of the multiobjective problem which is solved using a cooperative game-theoretic approach. The actuator locations and the cross-sectional areas of structural members are treated as design variables. Since the actuator locations are spatially discrete, whereas the cross-sectional areas are continuous, the optimization problem has mixed discrete-continuous design variables. A solution approach to this problem based on a hybrid optimization scheme is presented. The hybrid optimizer is a synergetic blend of artificial genetic search and gradient-based search techniques. The computational procedure is demonstrated through the design of an ACOSS-FOUR space structure. The optimum solutions obtained using the hybrid optimizer are shown to outperform the optimum results obtained using gradient-based search techniques.     

Three-dimensional core-shell hybrid solar cells via controlled in situ materials engineering

Three-dimensional core-shell organic-inorganic hybrid solar cells with tunable properties are demonstrated via electropolymerization. Air-stable poly(3,4-ethylenedioxythiophene) (PEDOT) shells with controlled thicknesses are rapidly coated onto periodic GaAs nanopillar arrays conformally, preserving the vertical 3D structure. The properties of the organic layer can be readily tuned in situ, allowing for (1) the lowering of the highest occupied molecular orbital level (|ΔE| ～ 0.28 eV), leading to the increase of open-circuit voltage (V(OC)), and (2) an improvement in PEDOT conductivity that results in enhanced short-circuit current densities (J(SC)). The incorporation of various anionic dopants in the polymer during the coating process also enables the tailoring of the polymer/semiconductor interface transport properties. Systematic tuning of the device properties results in a J(SC) of 13.6 mA cm(-2), V(OC) of 0.63 V, peak external quantum efficiency of 58.5%, leading to a power conversion efficiencies of 4.11%.     

The influence of reusing ‘Formtex’ controlled permeability formwork on strength and durability of concrete

The effects of the reuse of ‘Formtex’ Controlled Permeability Formwork (CPF) liner on strength and durability properties of concrete were investigated at two different water-cement ratios and the results are reported in this paper. Test blocks were cast using the CPF on one side and impermeable formwork (IF) on the opposite side of the mould so that direct comparisons could be made between the two. The strength was assessed using the Limpet pull-off tester and both the air permeability and the water absorption (sorptivity) were measured using the Autoclam Permeability System. Both these instruments measured the ‘covercrete’ properties. In addition, cores cut from the test specimens were subjected to an accelerated carbonation test and a chloride exposure test. The results showed that the ‘Formtex’ CPF increases the surface strength and the durability of concrete compared to the IF. There was an almost complete elimination of blowholes. The permeability of concrete decreased and its resistance to the ingress of both carbon dioxide and chlorides increased when CPF was used. The beneficial effects of the Formtex CPF were most evident in concrete of higher water-cement ratio. With the reuse of the Formtex liner twice, that is a total of three uses, the performance of the CPF to improve the properties of concrete remained almost the same. In this research the CPF liner was cleaned thoroughly between each use, which must be adhered to for site applications for reproducing the beneficial effects observed in the laboratory.     

pH-sensitive sodium alginate/calcined hydrotalcite hybrid beads for controlled release of diclofenac sodium

Objective: The aim of this study was to prepare pH-sensitive sodium alginate/calcined hydrotalcite (SA/CHT) hybrid bead with improved the burst release effect of the drug.

Materials and methods: A series of pH-sensitive SA/CHT hybrid beads were prepared by using Ca²⁺ cross-linking in the presence of diclofenac sodium (DS) and SA. The structure and drug loading of the beads were characterized by Fourier transform infrared spectroscopy and X-ray diffraction. The swelling and the drug release of the fabricated beads were investigated by the pH of test medium and CHT content.

Result: The formed positively charged hydrotalcite layers were adsorbed on the negatively charged SA polymer chains through electrostatic interaction and act as inorganic cross-linkers in the three-dimensional network. Compared to pure SA beads, the incorporation of CHT enhanced the drug encapsulation efficiency, improved the swelling behaviors and slowed the drug release from the hybrid beads.

Discussion and conclusions: The electrostatic interaction between hydrotalcite and SA has restricted the movability of the SA polymer chains, and then slowed down swelling and dissolution rates in aqueous solutions. The results provided a simple method to moderate drug release and matrix degradation of the SA beads.     

Synthesis and properties of siloxane-containing hybrid hydrogels: optical transmittance, oxygen permeability and equilibrium water content

Siloxane-containing hybrid hydrogels, coupled with optical transparency and moderate water content, have the advantage of a high oxygen permeability which gives rise to useful characteristics for extended wear contact lenses. To synthesize these hybrid hydrogels, free radical copolymerization of hydrophobic TRIS monomer/PDMS macromer with a hydrophilic monomer in a confined mold was studied. It proved that microphase separation of the resulting hybrid hydrogels, caused by inherent incompatibility between hydrophobic and hydrophilic monomers, could be controlled by either the hydrophobic/hydrophilic balance or molecular weight of PDMS macromer in the formulations, resulting in high optical transmittance (> 90%) at 400 nm. The oxygen permeability of the hybrid hydrogels at optimized formulations was also obtained as high as 83 barrers.     

Preparation and characterization of hybrid pH-sensitive hydrogels of chitosan-co-acrylic acid for controlled release of verapamil

In the present work crosslinked hydrogels based on chitosan (CS) and acrylic acid (AA) were prepared by free radical polymerization with various feed compositions using N,N methylenebisacrylamide (MBA) as crosslinking agent. Benzoyl peroxide was used as catalyst. Fourier transform infrared spectra (FTIR) confirmed the formation of the crosslinked hydrogels. This hydrogel is formed due to electrostatic interaction between cationic groups in CS and anionic groups in AA. Prepared hydrogels were used for dynamic and equilibrium swelling studies. For swelling behavior, effect of pH, polymeric and monomeric compositions and degree of crosslinking were investigated. Swelling studies were performed in USP phosphate buffer solutions of varying pH 1.2, 5.5, 6.5 and 7.5. Results showed that swelling increased by increasing AA contents in structure of hydrogels in solutions of higher pH values. This is due to the presence of more carboxylic groups available for ionization. On the other hand by increasing the chitosan content swelling increased in a solution of acidic pH, but this swelling was not significant and it is due to ionization of amine groups present in the structure of hydrogel. Swelling decreased with increase in crosslinking ratio owing to tighter hydrogel structure. Porosity and sol-gel fraction were also measured. With increase in CS and AA contents porosity and gel fraction increased, whereas by increasing MBA content porosity decreased and gel fraction increased. Furthermore, diffusion coefficient (D) and the network parameters i.e., the average molecular weight between crosslinks (M_c), polymer volume fraction in swollen state (V_2s), number of repeating units between crosslinks (M_r) and crosslinking density (q) were calculated using Flory-Rehner theory. Selected samples were loaded with a model drug verapamil. Release of verapamil depends on the ratios of CS/AA, degree of crosslinking and pH of the medium. The release mechanisms were studied by fitting experimental data to model equations and calculating the corresponding parameters. The result showed that the kinetics of drug release from the hydrogels in both pH 1.2 and 7.5 buffer solutions was mainly non-Fickian diffusion.