Alkaline phosphatase encapsulated in gellan-chitosan hybrid capsules

Alkaline phosphatase (ALP) was encapsulated in gellan-chitosan polyion complex (PIC) capsules using a convenient procedure. The recovery of ALP was about 50% when the capsules were prepared by dropping a solution of ALP and gellan mixture (ALP/gellan) into a chitosan solution. When p-nitrophenyl phosphate (p-NPP) and 5-bromo-4-chloro-3-indolyl phosphate (BCIP) were incubated with ALP/gellan-chitosan capsules as substrates for ALP, the transparent colorless capsules changed to yellow and blue, respectively. The encapsulation of ALP into the PIC capsules was also confirmed by SDS-PAGE and immunoblot analyses. The ALP and polypeptides of more than 30 kDa remained without release even after incubation at 4 degrees C for 14 d. The biochemical properties of the encapsulated ALP activity were similar to those of the intact enzyme. When the solution containing p-NPP was loaded on a column packed with ALP/gellan-chitosan capsules at 27 degrees C, approximately 75% of p-NPP was hydrolyzed by passing through the column. No significant leakage of ALP was observed during the procedure, indicating that the capsules were resistant to pressure in the chromatographic operation. Furthermore, 70% of the hydrolytic activity of the packed capsules remained after storage at 4 degrees C for one month. These results suggest that the polyion complex capsules could be useful materials for protein fixation without chemical modification. [Diagram: see text] Encapsulation of ALP into PIC capsules and the morphological changes seen in the absence of the ALP substrate and in the presence of p-NPP and BICP.     

Variable on-demand release function of magnetoresponsive hybrid capsules

Magnetoresponsive hybrid capsules formed with polyelectrolytes, amphiphile bilayers and Fe(3)O(4) nanoparticles were fabricated by a colloid-templating technique. Melamine-formaldehyde (MF) core particles with polyelectrolyte multilayer shell were prepared by layer-by-layer assembly. Fe(3)O(4) nanoparticles were additionally deposited on the capsular surface. Hollow capsules were obtained by the removal of the MF core particles. Amphiphile bilayer was finally coated on the obtained hollow capsules. The deposition amount of the Fe(3)O(4) nanoparticles is variable by changing the concentration of Fe(3)O(4) dispersion using for preparation of capsules. Encapsulated dyes were released on-demand by irradiation with an alternating magnetic field, due to a phase transition in the amphiphile membrane, induced by heating of the magnetic nanoparticles. The release rate of the hybrid capsules was controllable through controlling the deposition amount of Fe(3)O(4) nanoparticles on the capsules.     

Interface-directed self-assembly of gold nanoparticles and fabrication of hybrid hollow capsules by interfacial cross-linking polymerization

Amphiphilic gold nanoparticles (AuNPs) were produced at liquid-liquid interface via ligand exchange between hydrophilic AuNPs and disulfide-containing polymer chains. By using oil droplets as templates, hybrid hollow capsules with AuNPs on the surfaces were obtained after interfacial cross-linking polymerization. The volume ratio of toluene to water exerts an important effect on the size of capsules. The average size of the capsules increases with the volume ratio. Transmission electron microscopy (TEM), scanning electron microscopy (SEM), and atomic force microscopy (AFM) were used to characterize the hollow structures. In this research, not only one-component but also multicomponent hollow capsules were prepared by copolymerization of acrylamide and hybrid AuNPs at liquid-liquid interface. Because of the improvement in hydrophilicity of the hollow capsules, the average size of multicomponent capsules is bigger than one-component ones in aqueous solution.     

Hollow capsules formed in a single stage via interfacial hydrogen-bonded complexation of methylcellulose with poly(acrylic acid) and tannic acid

Hollow capsules can be prepared in a single stage by the interfacial complexation of methylcellulose (MC) with poly(acrylic acid) (PAA) or tannic acid (TA) via hydrogen bonding in aqueous solutions. The formation of capsules is observed when viscous solution of methylcellulose is added drop-wise to diluted solutions of polyacids under acidic conditions. The optimal parameters such as polymer concentration and solution pH for the formation of these capsules were established in this work. It was found that tannic acid forms capsules in a broader range of concentrations and pHs compared to poly(acrylic acid). The TA/MC capsules exhibited better stability compared to PAA/MC in response to increase in pH: the dissolution of TA/MC capsules observed at pH > 9.5; whereas PAA/MC capsules dissolved at pH > 3.8. The interfacial complexation can be considered as a potential single stage alternative to the formation of capsules using multistage layer-by-layer deposition method.     

胶束增强型聚电解质胶囊的结构研究

研究了胶束增强型聚电解质(PAH/PSS和PADA/PSS)胶囊在不同溶液环境中的形貌变化,发现这种新型的胶囊具有迥异于传统聚电解质胶囊的囊壁结构;研究了二维聚电解质复合膜与模板溶解液中嵌段共聚物PS-b-PAA胶束之间的相互作用,发现胶束层可以通过静电力与聚电解质胶囊囊壁相互作用.同时,模拟模板溶出后聚电解质胶囊内部的环境条件,研究了嵌段共聚物胶束在胶囊内部的存在状态及其在透析过程中的变化规律,认为共聚物可以通过疏水作用沉积于聚电解质复合膜的内壁,并通过Ca2+离子的桥联作用稳定,也就是在聚电解质复合膜层基础上又形成了一层胶束层.即这种胶束增强型聚电解质微胶囊的囊壁是由聚电解质层和胶束层所形成的双层结构.用这种双层结构模型,我们合理解释了胶囊在高盐离子浓度下的形貌变化.     

Fabrication of nanocapsules with Au particles trapped inside carbon and silica nanoporous shells

Carbon capsules with hollow cores and mesoporous shells (HCMS) containing entrapped Au particles were prepared by template replication from solid core/mesoporous shell silica spheres with encapsulated Au particles. The resulting HCMS carbon capsules were then nanocast one step further to generate Au-trapping hollow core silica capsules with nanostructured shells.     

Morphology control and 2D self-assembly of poly(styrene-co-divinylbenzene) capsules

In this paper, monodisperse poly(styrene-co-divinylbenzene) (PS-DVB) capsules with a bowl-like morphology were prepared controllably by regulating the content of DVB and dispersant. Using as-prepared PS-DVB capsules as building blocks, two-dimensional (2D) uniform hexagonal close-packed array with same orientation of each bowl was successfully fabricated by solvent evaporation. The size distribution showed that the capsules were still spherical in acetone before assembly and thus certified that the capsules caved in after self-assembly. Many factors including DVB content in capsules, experimental temperature and dispersants play important roles on regularity of orientation. Besides, "local self-assembly" array using multi-caved capsule as building blocks was obtained. More study proceeds with it, further advanced materials with complex functionalities or peculiar behavior could be expected.     

小分子液滴为模板制备有机-无机杂化纳米微胶囊

通过细乳液聚合,在正辛烷液滴外包覆一层苯乙烯与甲基丙烯酸-3-三甲氧基硅丙酯(MPS)的共聚物,制备了有机-无机杂化纳米微胶囊.通过透射电镜和动态光散射粒径仪观测其形态,用红外光谱表征了其分子结构.讨论了聚合方法对微胶囊制备的影响;通过溶度参数的计算和实验验证,发现配方中单体体积分数需小于36%才能得到微胶囊;通过界面自由能模型的计算和动力学分析,说明了微胶囊形成的热力学原因;发现共聚物中MPS的加入有利于微胶囊的形成,但若MPS的含量过大将会导致胶囊塌陷;最后阐明了这种微胶囊制备过程的机理.     

Calcium alginate gel as encapsulation matrix for coimmobilized enzyme systems

Encapsulation within calcium alginate gel capsules was used to produce acoimmobilized enzyme system. Glucose oxidase (GOD) and catalase (CAT) were chosen as model enzymes. The same values of V _max and K _mapp for the GOD encapsulated system and for the GOD-CAT coencapsulated system were calculated. When gel beads and capsules were compared, the same catalyst deactivation sequence for the two enzymes was observed. However, when capsules were employed as immobilization support, GOD efficiencies were higher than for the gel beads. These results were explained in terms of the structure of the capsules.     

LIGHT-SCATTERING STUDY OF POLYELECTROLYTE HOLLOW CAPSULES

Silver halide (AgX) microcrystal was used as template to synthesize hollow polyelectrolyte capsules. These hollow capsules were characterized by laser light scattering (LLS) used to measure the size of the capsules in solution. The ratio of hydrodynamic radius (Rh) from dynamic LLS to the radius of gyration (Rg) from static LLS is almost unity, revealing that the entities are hollow in solution. The results suggest that the LLS method can be regarded as a good complement to the confocal laser scanning microscopy (CLSM) method for the characterization of small hollow capsules, and it possesses the advantage of not needing fluorescence labeling.     

Modular assembly of layer-by-layer capsules with tailored degradation profiles

Herein we report the preparation of layer-by-layer (LbL) assembled, biodegradable, covalently stabilized capsules with tunable degradation properties. Poly(L-glutamic acid) modified with alkyne moieties (PGA(Alk)) was alternately assembled with poly(N-vinyl pyrrolidone) (PVPON) on silica particles via hydrogen-bonding. The films were cross-linked with a bis-azide linker, followed by removal of the sacrificial template and PVPON at physiological pH through hydrogen bond disruption, yielding one-component PGA(Alk) capsules. To control the kinetics and location of capsule degradation, a number of approaches were investigated. First, a degradable bis-azide cross-linker was incorporated into the inherently enzymatically degradable capsules. Second, we assembled low-fouling capsules composed of nondegradable poly(N-vinyl pyrrolidone-ran-propargyl acrylate) (PVPON(Alk)) via hydrogen bonding with poly(methacrylic acid) (PMA) and combined this with the aforementioned system (PGA(Alk)/PVPON) to produce stratified hybrid capsules. The degradation profiles of these stratified capsules can be closely controlled by the number as well as the position of nondegradable barrier layers in the systems. The facile tailoring of the degradation kinetics makes this stratified LbL approach promising for the design of tailored drug-delivery vehicles.     

pH-responsive capsules derived from nanocrystal templating

In the current work we demonstrate a facile and versatile way to create hydrophilic polymeric capsules by integration of Au nanocrystal templating, surface-initiated atom-transfer radical polymerization, and selective chemical cross-linking of polymer shells. Capsules of the homopolymer of 2-(dimethylamino)ethyl methacrylate and its copolymers with 2-(diethylamino)ethyl methacrylate and poly(ethylene glycol) methyl ether methacrylate were constructed. They swell at low pH and shrink at high pH. On the basis of the pH sensitivity of the resulting capsules, encapsulation and release of a drug model, rhodamine 6G, were realized. Furthermore, by cleaving Au-S bonds between Au cores and polymer shells, capsules containing free Au cores were generated, paving a simple pathway to introduce more functionality to the polymeric capsules.     

Engineering Multifunctional Capsules through the Assembly of Metal–Phenolic Networks

Metal–organic coordination materials are of widespread interest because of the coupled benefits of inorganic and organic building blocks. These materials can be assembled into hollow capsules with a range of properties, which include selective permeability, enhanced mechanical/thermal stability, and stimuli‐responsiveness. Previous studies have primarily focused on the assembly aspects of metal‐coordination capsules; however, the engineering of metal‐specific functionality for capsule design has not been explored. A library of functional metal–phenolic network (MPN) capsules prepared from a phenolic ligand (tannic acid) and a range of metals is reported. The properties of the MPN capsules are determined by the coordinated metals, allowing for control over film thickness, disassembly characteristics, and fluorescence behavior. Furthermore, the functional properties of the MPN capsules were tailored for drug delivery, positron emission tomography (PET), magnetic resonance imaging (MRI), and catalysis. The ability to incorporate multiple metals into MPN capsules demonstrates that a diverse range of functional materials can be generated.     

Fabrication of chitosan microcapsules via layer-by-layer assembly for loading and in vitro release of heparin

The heparin-loaded microcapsules were successfully prepared by layer-by-layer deposition of chitosan (CHI) and heparin (Hep). Film growth was confirmed by the reversal of ζ-potentials during polysaccharide deposition. Both scanning electron microscopy and transmission electron microscope evidenced the integrity of (CHI/Hep)₅ capsules after the removal of cores. By assembling the carriers with chitosan that are inherently degradable, the capsules were engineered to degrade specifically in the presence of lysozyme. It was demonstrated that the loaded heparin was released from the capsules over a long period of time when being incubated in lysozyme solution. With these results, such CHI/Hep capsules may have a great potential as controlled release carrier for heparin.     

Functional improvement of porcine neonatal pancreatic cell clusters via conformal encapsulation using an air-driven encapsulator

Transplantation of islet cells into diabetic patients is a promising therapy, provided that the islet cells are able to evade host immune rejection. With improved islet viability, this strategy may effectively reverse diabetes. We applied 2% calcium alginate to generate small and large capsules to encapsulate porcine neonatal pancreatic cell clusters (NPCCs) using an air-driven encapsulator. After encapsulation, the viability was assessed at 1, 4, 7, 14 and 28 days and secretion of functional insulin in response to glucose stimulation were tested at days 14 and 28. Selective permeability of the small alginate capsules was confirmed using various sizes of isothiocyanate-labeled dextran (FITC-dextran). Encapsulation of NPCCs was performed without islet protrusion in the small and large capsules. The viability of NPCCs in all experimental groups was greater than 90% at day 1 and then gradually decreased after day 7. The NPCCs encapsulated in large capsules showed significantly lower viability (79.50 ± 2.88%) than that of naïve NPCCs and NPCCs in small capsule (86.83 ± 2.32%, 87.67 ± 2.07%, respectively) at day 7. The viability of naïve NPCCs decreased rapidly at day 14 (75.67 ± 1.75%), whereas the NPCCs encapsulated in small capsules maintained (82.0 ± 2.19%). After 14 and 28 days NPCCs' function in small capsules (2.67 ± 0.09 and 2.13 ± 0.09) was conserved better compared to that of naïve NPCCs (2.04 ± 0.25 and 1.53 ± 0.32, respectively) and NPCCs in large capsules (2.04 ± 0.34 and 1.13 ± 0.10, respectively), as assessed by a stimulation index. The small capsules also demonstrated selective permeability. With this encapsulation technique, small capsules improved the viability and insulin secretion of NPCCs without islet protrusion.     

Tunable morphologies of polymer capsules templated from cuprous oxide particles for control over cell association

Over the past two decades,layer-by-layer(LbL) assembly of micro/nanocapsules has been of interest for the investigation of bio-nano interactions to explore bio-applications,such as drug delivery.The choice of an appropriate template that can be easily dissolved under mild conditions is one of the challenges for the assembly of LbL capsules.Herein,we report the engineering of LbL capsules with tunable morphologies using cuprous oxide(Cu_2O) particles as templates.Cu_2O particles with cubic,tetradecahedral or spherical morphologies were synthesized via hydrothermal processes,which can be dissolved under mild condition(e.g.,sodium thiosulfate solution).The influence of capsule morphologies on cell association was investigated,which indicates that LbL capsules with cubic geometry promoted cell association up to 4 and 9-fold than tetradecahedral and spherical capsules,respectively.The reported method provides a new avenue for the assembly of LbL capsules with different morphologies,which has the potential for better understanding of biological interactions of LbL capsules.     

ICP-MS法测定山绿茶降压胶囊无机元素及其质量评价

目的建立了电感耦合等离子体质谱法(ICP-MS)测定不同批次山绿茶降压胶囊内容物中无机元素的含量,从无机元素角度探讨山绿茶降压胶囊的质量控制方法。方法采用微波消解处理山绿茶降压胶囊内容物样品,用ICP-MS对样品中多种无机元素进行全定量测定。结果测定10个不同批次山绿茶降压胶囊内容物的22种无机元素,其中K、Mg、Ca、Zn等元素含量较高,且与药效相关性较强,Cu、As、Hg、Pb、Cd全部符合标准要求。结论本法灵敏度高,专属性好,适用于山绿茶降压胶囊内容物中无机元素测定,为山绿茶降压胶囊内容物重金属含有量及用药提供依据。     

Effect of different molecular weights of polyethylene glycol as a plasticizer on the formulation of dry powder inhaler capsules: Investigation of puncturing size,morphologies, and surface properties

Today, the principle of research and development is pulmonary drug delivery due to the potential for maximizing therapeutic effects for patients by direct drug targeting the pathology site in the lungs. Amongst the convenient delivery alternatives, the Dry Powder Inhaler (DPI) is the preferred device to remedy a variety of diseases. In this regard, the fabrication and development of a novel formulation for DPI capsules have been studied. We investigated the effects of various parameters, such as percentages of polyethylene glycol (PEG), propylene glycol (PG), glycerol (Gly), brittleness, test conditions, and particle release of manufactured DPI capsules. The efficacy of each parameter was evaluated in detail to understand and address the consequences of the mentioned factors. The results illustrated that the lower molecular weight of PEGs presented the better plasticizing capability of gelatin. Owing to the hygroscopicity of the utilized plasticizer, polyethylene glycol 400 (PEG 400) increased the capsule flexibility for a longer time and its stability under environmental conditions in the gelatin capsule formulation. Likewise, no particle release was observed in the gelatin/PEG capsule. The prepared gelatin/PEG400 capsules were compared with pure gelatin and HPMC capsules. The capsules were evaluated in terms of loss on drying (LOD), surface morphology, roughness, and puncture type. The results show that using PEG-400 can lead to the production of capsules that have low moisture content and minimal interaction with APIs. In addition, gelatin/PEG capsules have no particles due to the smooth surface after the punching process. The as-produced capsules are not blocked again after punching, allowing the patient to take the drug completely. In fact, the present research provided substantial insight regarding the development of DPI formulation in capsule investigations on an industrial scale.     

Hollow carbonaceous capsules from glucose solution

An easy hydrothermal method was developed for preparing hollow carbonaceous capsules with reactive surface layer and tunable void size, and shell thickness through a hydrothermal method at 180 degrees C, using only the anionic surfactant sodium dodecyl sulfate (SDS) and glucose as starting material. Ag nanoparticles of less than 10 nm were loaded onto the surface of capsules under ambient condition. Products were characterized with TEM, SEM, and FT-IR spectra. The process is green, cheap, and easy. Since no toxic materials were used in preparation and as-prepared capsules a shared reactive surface layer and a stable carbonaceous framework, the capsules might find application in fields such as biochemistry, pharmaceutics, and clinical diagnostics.     

The shell dissolution of various empty hard capsules

The shell dissolution properties of gelatine, gelatine/polyethylene glycol (PEG) and hydroxypropyl methylcellulose (HPMC) capsules were studied as a function of temperature, dissolution medium, and after different storage conditions. In any dissolution medium with a pH below or equal to 5.8, HPMC capsule shells dissolved rapidly, and there was no difference in the time in which dissolution occurred in the tested temperature interval of 10 to 55 degrees C. Gelatine and gelatine/PEG capsule shells, generally, did not dissolve at temperatures below 30 degrees C. The shell dissolution time of all capsules tested was prolonged and more variable in mixed phosphate buffer pH = 6.8. The addition of enzymes (pepsin, pancreatin) to any dissolution medium was found not to enhance the differences between the different types of capsules investigated. In practical terms, the results indicated that capsule formulations should not be taken with drinks from the carbonated Cola-type. Gelatine containing capsules should preferably be administered with a warm drink, whereas HPMC capsules could be given with cold or warm drinks. The latter type of capsules should also be preferred for preparations to be taken in the fasted state. A short storage of gelatine containing capsules under hot humid tropical conditions appeared not to alter the dissolution properties of the shells, and changes in disintegration times and dissolution times of formulations filled in such capsules might be a reflection of changes of the powders incorporated rather than of the capsule shells. However, a short storage of HPMC capsules under such conditions appeared to influence the capsule shell matrix.