Influence of folate conjugation on the cellular uptake degree of poly(allylamine hydrochloride) microcapsules

The microcapsules in drug delivery systems can prevent degradation of drugs and help to control the release rate. To enhance the targeted delivery effect of the microcapsules to cancer cells, some specific ligands such as folic acid (FA) are necessarily further conjugated. Herein, covalent poly(allylamine hydrochloride) (PAH) multilayers were fabricated on CaCO₃ microparticles under the cross‐linking of glutaraldehyde, which were further immobilized with different amount of FA molecules via the spacer of diamino terminated poly(ethylene glycol) (PEG). As a comparison study, four types of microcapsules, i.e., the PAH capsules, the PAH capsules grafted with PEG, and the PAH capsules conjugated with two different amount of FA via the PEG spacer were prepared. Their chemical and physical structures were confirmed by infrared spectroscopy, UV–vis spectroscopy and scanning electron microscopy. In vitro cell culture found that the cellular uptake of the PAH capsules grafted with PEG was reduced significantly compared with that of the pure PAH capsules. The FA‐modified microcapsules could be selectively delivered into HepG2 tumor cells which overexpress FA receptors but not into the endothelial cells. The number of HepG2 cells which ingested the FA‐conjugated capsules showed a positive correlation with FA amount. The results indicate that these FA conjugated capsules have a high selectivity to be delivered to tumor cells, endowing them with a larger opportunity functioning as targeted delivery vehicle for anticancer drugs. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

以ZnO微球为模板制备硫酸葡聚糖/鱼精蛋白胶囊及其缓释行为

以ZnO微球为模板,利用层层自组装的方法制备了壁材为鱼精蛋白(PRM)和硫酸葡聚糖(DXS)的生物可降解聚电解质胶囊. ZnO微球呈良好的单分散性,具有5 nm以上的中孔,装载荧光素后生成荧光微球. 在ZnO微球外交替吸附鱼精蛋白和硫酸葡聚糖,制得核-壳型ZnO/(DXS/PRM)8复合微球;采用稀HAC溶液去除ZnO模板后,可生成(DXS/PRM)8胶囊. 以水溶性多柔米星药物分子作为目标物,研究了该胶囊的载药和释放行为. 结果显示,该(DXS/PRM)8胶囊对多柔米星药物分子具有明显的缓释性.     

分子识别型智能微囊的制备及其控制释放特性

采用微流控乳化和紫外光照引发制备聚(N-异丙基丙烯酰胺-共聚-丙烯酸)微囊,然后通过缩合反应将氨基化β-环糊精(ECD)引入微囊成功制备得到聚(N-异丙基丙烯酰胺-共聚-丙烯酸/氨基化β-环糊精)(PNA-ECD)微囊。PNA-ECD微囊具有明显的核壳型结构和良好的单分散性。微囊的平均直径为470μm,CV值为2.98%。PNA-ECD微囊在识别模型芳环分子8-苯胺-1-萘磺酸铵盐(ANS)后能等温收缩从而实现对内载药物的控制释放。32℃时,微囊内部的模型药物异硫氰酸荧光素标记葡聚糖(FITC-dextran)在纯水中无明显释放,而在加入2.0mmol/L ANS溶液16min后,微囊内部约70%的FITC-dextran释放到微囊外部。研究结果对制备单分散分子识别型智能微囊及研究其控制释放特性提供有价值的理论指导和实验基础。     

Permeability of Ibuprofen in Various Polyelectrolyte Multilayers

Ibuprofen microcrystals sized between 25–45 μm have been encapsulated with various types of polyelectrolyte multilayers (PEMs) constructed with polyallylamine (PAH), polyethylenimine (PEI) or poly(4‐vinylpyridine) (P4VP) as polycations and polystyrenesulfonate (PSS), polyanetholesulfonate (PAS) and dextran sulfate (DEXS) as polyanions. The release of ibuprofen from the microcapsules was monitored in situ by UV‐vis spectroscopy for the quantitative characterization of PEM permeability. Our results revealed that PEMs formed by PAH/DEXS, PEI/PSS, P4VP/PSS and P4VP/PAS are highly permeable to ibuprofen because their film cavities are much larger than the size of ibuprofen molecules. The PEMs formed by PAH/PSS and PAH/PAS are less permeable to ibuprofen due to their smaller film cavities. It is believed that the high charge density and well‐matched charge interactions between the coupling polyions in PAH/PSS and PAH/PAS multilayers allow the films to form small cavities. In addition, it was found that the permeability coefficient of PEMs decreases with increasing multilayer thickness before the film reaches a certain number and achieves structural homogeneity. Above that, the permeability coefficient remains constant with further increase of film thickness.     

肠靶向海藻酸钙基微胶囊的制备及控释性能研究

利用毛细管共挤出技术结合静电吸附和仿生硅化的方法,制备了海藻酸钙-壳聚糖/精蛋白/二氧化硅(ACPSi)复合微胶囊。ACPSi复合微胶囊的平均粒径约3.18 mm,单分散性好,囊壁最外层的二氧化硅层可抑制其在肠液pH环境中的溶胀,增强囊的机械稳定性。将羟丙甲基纤维素邻苯二甲酸酯(HPMCP)肠溶微球作为释药“微阀门”,嵌入囊壁可以更好地控制微胶囊的释药行为。以吲哚美辛为模型药物,当药物浓度为22.5 mg/ml时,ACPSi载药微胶囊在pH 2.5模拟胃液中3 h时累计释药率仅为0.33%,而转移至pH 6.8模拟肠液中19 h时累计释药率为77.78%;囊壁嵌入HPMCP微球后,22 h时累计释药率可提高约4%。因此,该复合微胶囊具有良好的肠靶向作用和控释特性,作为口服肠靶向缓控释制剂具有良好的应用前景。     

Microcapsules prepared from a polycondensate‐based cement dispersant via layer‐by‐layer self‐assembly on melamine‐formaldehyde core templates

Novel microcapsules were prepared from colloidal core–shell particles by acid dissolution of the organic core. Weakly crosslinked, monodisperse and spherical melamine‐formaldehyde polycondensate particles (diameter ～ 1 μm) were synthesized as core template and coated with multilayers of an anionic polyelectrolyte via layer‐by‐layer deposition technique. As polyelectrolytes, an anionic naphthalenesulfonate formaldehyde polycondensate that is a common concrete superplasticizer and thus industrially available, and cationic poly(allylamine hydrochloride) were used. Core removal was achieved by soaking the core–shell particles in aqueous hydrochloric acid at pH 1.6, resulting in hollow microcapsules consisting of the polyelectrolytes. Characterization of the template, the core–shell particles, and the microcapsules plus tracking of the layer‐by‐layer polyelectrolyte deposition was performed by means of zeta potential measurement and scanning electron microscopy. The microcapsules might be useful as microcontainers for cement additives. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Preparation of polyelectrolyte giant capsules using cross-linked alginate gels as core material

Polyelectrolyte giant capsules whose diameter is in a millimeter level were prepared by a layer-by-layer deposition of poly(allylamine hydrochloride) (PAH) and poly(styrene sulfonate) (PSS) on an alginate (AGA)-Ca²⁺ sphere followed by dissolution of the AGA core in an ethylenediaminetetraacetic acid or NaCl solution. A fluorescent-labeled bovine serum albumin (BSA) was successfully encapsulated in the PAH/PSS polyelectrolyte capsule. The release of the BSA from the capsule was suppressed in the presence of higher concentration of salt, while the effect of pH was small. In addition, the thickness of the PAH/PSS layer in the capsule wall gave an effect on the release rate of the BSA.     

基于纤维素模板的聚合物空心微球作为药物载体的性能研究及分析

以羟丙基纤维素为模板材料,分别采用不同的聚合方法制备了2种不同形态和结构的聚合物空心微球--聚N-异丙基丙烯酰胺-co-聚丙烯酸(PNIPAm-co-PAA)微凝胶和聚N-异丙基丙烯酰胺-聚丙烯酸(PNIPAm-PAA)水凝胶微囊。以盐酸阿霉素(Dox)作为模型药物,考察了聚合物空心微球作为药物载体的载药能力和体外释放性能。研究表明,PNIPAm-co-PAA微凝胶、PNIPAm-PAA水凝胶微囊和Dox分子能够通过正负电荷的相互吸引实现有效结合;载药微球具有良好的缓释性能,并对Dox的释放表现出明显的pH值敏感性和温度敏感性。体外细胞毒性实验表明,载药PNIPAm-co-PAA微凝胶、PNIPAm-PAA水凝胶微囊具有很高的抗肿瘤活性,细胞相对存活率均可达20%左右。PNIPAm-co-PAA微凝胶、PNIPAm-PAA水凝胶微囊在作为水溶性药物或蛋白类药物载体方面,具有潜在的应用价值,同时有望应用于木材胶黏剂防腐等。     

以三聚氰胺甲醛微球为模板的空腔胶囊的制备与应用

以低度交联的单分散三聚氰胺甲醛(MF)微球作为胶体模板,采用逐层静电自组装技术,交替组装正负聚电解质,得到具有核壳结构的复合微球,然后利用盐酸溶液分解掉模板MF,从而形成均匀的空腔胶囊;并以盐酸阿霉素为例,对空腔胶囊的载药量及缓释性进行了初步研究. 结果显示,胶囊载药量可达27.07 μg/mL,胶囊对药物具有显著的缓释作用,释放半衰期t1/2=17.5 h.     

Investigation of the influence of temperature on polyelectrolyte microcapsules

The heat sensitivity of hollow polyelectrolyte microcapsules consisting of an even or odd number of alternating layers of poly(allylamine) and poly(styrenesulfonate) is investigated by light scattering and confocal microscopy. The polyelectrolyte microcapsules are prepared using CaCO₃ microspherulites as “core” dispersed particles. It is demonstrated that the size of capsules with an even or odd number of layers decreases with an increase in the temperature and time of heat treatment. The heat sensitivity of the polyelectrolyte microcapsules is estimated from the activation energy required for changing the parameters of their initial structure under heating. It is shown that the heat sensitivity of the polyelectrolyte microcapsules with an odd number of layers is higher than the heat sensitivity of the polyelectrolyte microcapsules with an even number of layers. A possible mechanism responsible for the change in the structural parameters of the microcapsules upon heat treatment is proposed.     

快速膜乳化法制备载醋酸曲普瑞林PLGA微球

以生物可降解聚合物聚(乳酸?羟基乙酸)(PLGA)为载体,以160 g/L明胶水溶液为内水相、含500 g/L PLGA的二氯甲烷为油相,采用快速膜乳化和溶剂蒸发法制备了粒径均一的载醋酸曲普瑞林PLGA微球,微球粒径约30 mm,粒径分布系数Span<0.8,醋酸曲普瑞林包埋率达80.12%,药物在磷酸盐缓冲液中释放36 d的释放率为72.60%,体外释放行为良好.     

Design of intelligent chitosan/heparin hollow microcapsules for drug delivery

In this study, a novel strategy has been developed for the assembly of polyelectrolyte multilayer (PEM) on CaCO₃ templates in acidic pH solutions, where consecutive polyelectrolyte layers (heparin/poly(allylamine hydrochloride) or heparin/chitosan) were deposited on PEM hollow microcapsules established previously on CaCO₃ templates. The PEM build‐up, hollow capsule characterization and successful encapsulation of fluorescein 5(6)‐isothiocyanate (FITC)‐Dextran by coprecipitation with CaCO₃ are demonstrated. Improvement by the removal of CaCO₃ core was achieved while the depositions. In the course of the release profile, high retardation for encapsulated FITC‐Dextran was observed. The combined shell capsules system is a significant trait that has potential use in tailoring functional layer‐by‐layer capsules as intelligent drug delivery vehicles where the preliminary in vitro tests showed the responsiveness on the enzymes. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 44425.     

Structure and mechanical properties of polylactide copolymer microspheres and capsules

Polylactide homopolymers, polylactide and poly(ethylene oxide) diblock and triblock copolymers are used to prepare spherical microparticles by using the single oil-in-water emulsion and solvent evaporation technique. We are able to create both bulk and hollow microspheres by altering the conditions of preparation. The experiments are carried out at two fixed temperatures of 15 and 22 °C. We show, from scanning electron microscopy data, that the microspheres produced from the homopolymers are bulk and homogeneous at both temperatures whereas they are hollow when the triblock copolymers are used. The diblock copolymers yield bulk microspheres at 15 °C and microcapsules at 22 °C. Compression experiments emphasize once more the inner morphology of the spheres. As it is expected, bulk microspheres have higher Young’s modulus than the microcapsules. Nevertheless, comparative compression analysis of both morphologies shows that the microcapsules retain relatively high compressive moduli. These results have implications for the design of rigid and biodegradable microcapsules.     

Monodisperse temperature-responsive hollow polymer microspheres: Synthesis, characterization and biological application

Temperature-responsive hollow poly(N-isopropylacrylamide) (PNIPAAm) microspheres were prepared by a two-stage distillation precipitation polymerization to afford a core-shell microspheres with subsequent removal of poly(methacrylic acid) (PMAA) core. PMAA@PNIPAAm core-shell microspheres were synthesized by the second-stage polymerization of NIPAAm in the presence of PMAA as core with N,N′-methylenebisacrylamide as crosslinker in acetonitrile, in which the hydrogen-bonding interaction between the carboxylic acid group of PMAA core and the amide group of NIPAAm as well as MBAAm played a key role to form the core-shell microspheres. The hollow PNIPAAm microspheres with different thicknesses, which were controlled by the monomer loading level and the crosslinking degree, were developed after the removal of PMAA core. The loading and controlled-release behavior of the drug on the hollow PNIPAAm microspheres was investigated with doxorubicin hydrochloride. The core-shell and hollow microspheres were characterized with transmission electron microscopy, scanning electron microscopy, dynamic light scattering, static light scattering, X-ray photoelectron spectroscopy, elemental analysis, and FT-IR spectra.     

Polymerization of pyrrole on a polyelectrolyte hollow-capsule microreactor

‘Caved-in’ and spherical polypyrrole (PPy) capsules were successfully prepared by direct polymerization of pyrrole on polyelectrolyte hollow-capsule microreactors at different conditions. This microreactor was formed by alternate layer-by-layer (LbL) adsorption of chitosan (CS) and poly(sodium 4-styrenesulfonate) (PSS) on polystyrene (PS) colloidal particle and followed by removing the PS core with tetrahydrofuran (THF). The integrity and self-sustaining of the microreactor could be ensured through the chemical cross-linking of CS in multilayers with glutaraldehyde before the removing of PS. The direct polymerization of pyrrole on the microreactor, either polycations or polyanions at the outmost layer, can be achieved according to hydrogen bonding effect or electrostatic interaction. Participation of inorganic salts plays a significant role on morphology controllable of intact hollow polypyrrole capsules.     

Photochemical rupture of microcapsules: A model system

Polyamide microcapsules containing solutions of azo-bis-isobutyronitrile (AIBN) were prepared and characterized as regards diameter and wall thickness. Under UV irradiation the AIBN eliminates nitrogen, and this, under suitable conditions, leads to rupture of the capsules. The influence of capsular diameter and wall thickness of the crosslinking agent silane, of AIBN concentration, and of light intensity on the photoelimination and rupture were studied by determining rates of nitrogen release and by microscopic examination. The results are interpreted in terms of release of nitrogen in the core followed by diffusion of nitrogen or of core solution through the walls, or rupture of the microcapsules. The application to controlled photochemical release of contents is considered.     

Preparation and characterization of hollow microcapsules for use as ultrasound contrast agents

A laboratory-scale method of producing micron-sized hollow microscapsules from a biodegradable polymer such as 50/50 poly(D, L-lactide-co-glycolide) (PLGA), for use as a diagnostic ultrasound contrast agent, was developed. The technique involved microencapsulation of a volatile solid core material, and subsequent sublimation of the core to leave a hollow microsphere. A core material, such as ammonium carbonate, was ground to a suitable size distribution and encapsulated by a modified solvent evaporation or coacervation technique. This study investigated process parameters to produce diagnostically viable microscapsules by these two en-capsulation methods, such as polymer molecular weight (from 10,000 to 50,000), initial polymer concentration, agitation method, and stabilizer type. Polymer solution viscosity, polydispersity, and agitation rates significantly controlled the mean size of the microcapsules. Stabilizers were essential in solvent evaporation, but corrupted the morphology of spheres made by coacervation. Zeta potential values of microsphere dispersions revealed differences in surface characteristics between both encapsulation methods. Incubation of microcapsules with serum improved their dispersion in aqueous media. Preliminary in vivo ultrasound studies with the New Zealand white rabbit model, using color Doppler, showed that the microcapsules gave significant contrast in the right kidney.     

Microfluidics for producing polylactide nanoparticles and microparticles and their drug delivery application

This review presents use of the microfluidics technique for the preparation of polylactide (PLA) based particles for developing novel drug delivery systems. Droplet‐based microfluidics allow uniform single, double and higher order emulsions to be generated that yield highly uniform microspheres, microcapsules and polymersomes. Typically, the building blocks of these complex microparticle systems are PLA macromolecules, their copolymers with different comonomers and recently stereocomplexes composed of an equimolar mixture of poly(l ‐lactide) and poly(d ‐lactide). In addition, the technique offers several advantages over conventional emulsion methods and the highly uniform droplets obtained allow for encapsulation of small drug molecules in polymer network meshes or within their hollow interior. The novel approach in this area is to use the microfluidics technique to produce nanoparticles in the microfluidics channel by micromixing/nanoprecipitation in glass capillary devices. Therefore, this review is divided into three main sections in which we discuss the formation of microspheres from single emulsion droplets, microcapsules and polymersomes from higher order emulsion droplets, and nanoparticles from nanosuspensions in a microfluidic channel. Finally, we compare the drug release from these different particles, focusing mainly on those formed from sensitive or supramolecular networks. © 2018 Society of Chemical Industry     

包覆多层聚电解质/树状大分子的聚合物微球表面CdS纳米粒的形成

将聚酰胺-胺(PAMAM)树形大分子、聚对苯乙烯磺酸钠(PSS)和聚二烯丙基二甲基氯化铵(PDADMAC)在三聚氰胺甲醛(MF)微球上进行静电自组装,制得聚电解质壳层的核壳式微球. 通过反应沉积吸附方法生成具有稳定荧光性能的CdS/聚电解质核壳式复合微球. 用透射电镜表征复合微球形貌,用反射紫外和荧光表征了CdS/聚电解质核壳式复合微球的光学特性.