Permeability Of Capsules Research Articles

Oxidative stability and oxygen permeability of oil-loaded capsules produced by spray-drying or electrospraying measured by electron spin resonance

The oxidative stability and the oxygen permeability of oil-loaded capsules were investigated by Electron Spin Resonance (ESR). The capsules were produced by spray-drying or electrospraying in the monoaxial or coaxial configuration using glucose syrup as the encapsulating agent. ESR-spin trapping results showed that electrosprayed capsules oxidized faster and during the early stages of incubation, irrespective of the emitter configuration (monoaxial or coaxial), when compared to those produced by spray-drying. Furthermore, ESR oximetry showed that oxygen inside the spray-dried capsules reached equilibrium with the surrounding atmosphere significantly slower than the monoaxially electrosprayed capsules (i.e., ∼2h and ∼10 min, respectively). These findings have been attributed to the larger particle size of the spray-dried capsules influencing the oxygen diffusion area (i.e., lower surface-to-volume ratio) and diffusion path (i.e., thicker encapsulating wall for a fixed oil load). Together, the lower oxygen uptake reported for the spray-dried capsules correlated well with their higher oxidative stability.

Numerical method to characterise capsule membrane permeability for controlled drug delivery.

Design and characterisation of capsules is not an easy task owing to the multiple involved preparation factors and parameters. Here, a novel method to characterise capsule membrane permeability to solute molecules by an inverse approach is proposed. Transport of chemical species between the capsule core and the surrounding medium through the membrane is described by the Fick's second law with a position-dependent diffusion coefficient. Solutions are computed in spherical coordinates using a finite difference scheme developed for diffusion in multilayer configuration. They are validated using semi-analytical solutions and fully three-dimensional lattice Boltzmann simulations. As a proof of concept, the method is applied to experimental data available in the literature on the kinetics of glucose release and absorption to determine the membrane permeability of capsules. The proposed method is easy to use and determines correctly the permeability of capsule membranes for controlled drug release and absorption applications.

A novel bilayered expanded polytetrafluoroethylene glaucoma implant creates a permeable thin capsule independent of aqueous humor exposure.

The purpose of these studies was to evaluate clinical, functional, and histopathological features of glaucoma drainage implants (GDIs) fabricated from novel, custom‐tailored expanded polytetrafluoroethylene (ePTFE). Implants of matching footprints were fabricated from silicone (Control) and novel, bilayered ePTFE. ePTFE implants included: (a) one that inflated with aqueous humor (AH) (High), (b) one that inflated with a lower profile (Low), (c) an uninflated implant not connected to the anterior chamber (Flat), and (d) one filled with material that did not allow AH flow (Filled). All implants were placed in adult New Zealand White rabbits and followed over 1–3 months with clinical exams and intraocular pressure. The permeability of tissue capsules surrounding GDIs was assessed using constant‐flow perfusion with fluoresceinated saline at physiologic flow rates. After sacrifice, quantitative histopathological measures of capsule thickness were compared among devices, along with qualitative assessment of cellular infiltration and inflammation. Capsular thickness was significantly reduced in blebs over ePTFE (61.4 ± 53 μm) versus silicone implants (193.6 ± 53 μm, p = .0086). AH exposure did not significantly alter capsular thickness, as there was no significant difference between High and Filled (50.9 ± 29, p = .34) implants. Capsules around ePTFE implants demonstrated permeability with steady‐state pressure: flow relationships at physiologic flow rates and rapid pressure decay with flow cessation, while pressure in control blebs increased even at low flow rates and showed little decay. Perfused fluorescein dye appeared beyond the plate border only in ePTFE implants. ePTFE implants are associated with thinner, more permeable capsules compared to silicone implants simulating presently used devices.

Oxygen permeability and oxidative stability of fish oil-loaded electrosprayed capsules measured by Electron Spin Resonance: Effect of dextran and glucose syrup as main encapsulating materials

The oxygen permeability and oxidative stability of fish oil-loaded electrosprayed capsules were studied by Electron Spin Resonance (ESR). Electrosprayed capsules with dextran as main biopolymer showed a significantly faster broadening (ΔHpp) of 16-doxyl-stearate ESR spectrum when compared to glucose syrup capsules. This finding indicates a higher oxygen permeability of dextran capsules than glucose syrup capsules, which is explained by a reduced average free volume in the glucose syrup matrix than in the dextran shell. Moreover, glucose syrup capsules showed a significantly lower increase in the peak-to-peak amplitude of N-tert-butyl-α-phenylnitrone (PBN) ESR spectrum during storage when compared to dextran capsules. This implies a higher oxidative stability of glucose syrup capsules than dextran capsules, which correlated well with the lower oxygen permeability of the former. These results indicated the importance of the oxygen barrier properties of the wall materials when encapsulating long chain omega-3 polyunsaturated fatty acids by electrospraying.

Bioinspired capsules based on nanocellulose, xyloglucan and pectin – The influence of capsule wall composition on permeability properties

Materials based on renewable biopolymers, selective permeability and stimuli-responsive release/loading properties play an important role in biomedical applications. Here, in order to mimic the plant primary cell-wall, microcapsules have been fabricated using cell wall polysaccharides, namely pectin, xyloglucan and cellulose nanofibers. For the first time, a large amount of xyloglucan was successfully included in such capsules. These capsules demonstrated stimuli-responsive (ON/OFF) permeability and biocompatibility. The live cell staining revealed that the microcapsules’ surface enhanced cell growth and also the non-toxic nature of the microcapsules. In water, the microcapsules were completely and partially permeable to fluorescent dextrans with an average molecular weight of 70 kDa (hydrodynamic diameter of ca. 12 nm) and 2000 kDa (ca. 54 nm), respectively. On the other hand, the permeability dropped quickly when the capsules were exposed to 250 mM NaCl solution, trapping a fraction of the 70 kDa dextrans in the capsule interior. The decrease in permeability was a direct consequence of the capsule-wall composition, i.e. the presence of xyloglucan and a low amount of charged molecules such as pectin. The low permeability of capsules in saline conditions (and in a model biological medium), combined with a capsule wall that is made from dietary fibers only, potentially enables their use in biological applications, such as colon targeted delivery in the gastro-intestinal tract. Statement of SignificanceFor the first time, microcapsules have been prepared that possess capsule walls that mimic the primary cell wall found in natural plant cells. The capsules were assembled using pectin, xyloglucan and cellulose in the form of cellulose nanofibers. The capsules demonstrated stimuli-responsive (ON/OFF) permeability and biocompatibility. The low permeability of capsules in saline conditions (and in a model biological medium), combined with a capsule wall that is made from dietary fibers only, potentially enables their use in biological applications, such as colon targeted delivery in the gastro-intestinal tract. Such model plant cell capsules might also further improve the understanding for the digestion and release of nutrients from natural plant cells found in vegetables and fruits.

Photo-crosslinked natural polyelectrolyte multilayer capsules for drug delivery

Polyelectrolyte multilayer (PEM) capsules have been widely investigated in drug delivery systems in past two decades, but still remain challenging for their uncontrolled release properties and kinetics. One way to control diffusion-based drug release is to crosslink the PEMs so that the permeability of capsules can be decreased and thus, the encapsulated drugs could be released with respect to the changes of chemical, physical or biological conditions. The photo-crosslinking method is approximately 16 times faster than the normal chemical methods. We hereby present a fast photo-crosslinking method of chitosan-alginate PEM capsules, which allows effectively decreasing the diffusion of the encapsulated components across the PEM walls of capsules. The experimental results show that photocrosslinked capsules exhibit a significantly lower release rate of anticancer drug, doxorubicine compared to non-crosslinked capsules, demonstrating the usability of this method in controlled drug delivery and biomedical applications.

Poly(N-isopropylacrylamide)/poly(dopamine) capsules.

Polymer capsules are an interesting concept considered in nanobiotechnology. Approaches that facilitate their assembly remain sought after. Poly(dopamine) (PDA) has been considered and successfully applied in this context. We recently demonstrated that PDA could be copolymerized with different types of poly(N-isopropylacrylamide) (pNiPAAm) to assemble mixed films on planar substrates. Herein, we transferred this approach onto colloidal substrates and characterized the film thickness depending on the film composition and template particles size. While the membrane of capsules assembled using 5 μm template particles exhibited strong dependency on the film composition, smaller templates led to capsules with similar membrane thickness. We then compared the permeability of different capsules using fluorescently labeled dextran and fluorescein. We found that the permeability of capsules was heavily dependent on the polymer composition and the template particle size. These fundamental findings contribute to the potential of these capsules, assembled in one-step, for biomedical applications.

Stimuli‐Responsive Capsules Prepared from Regenerated Silk Fibroin Microspheres

Microcapsules are synthesized via the self-assembly of silk-fibroin microspheres with polycaprolactone in a colliodosome preparation procedure. The microsphere building blocks with controlled diameter are prepared from the naturally occurring biopolymer, silk fibroin, and then act as stabilizers for oil-in-water (O/W) emulsion and organized themselves on the surface of chloroform droplets to form the capsules. The concentration of the protein-based microspheres and the binding polycacrolactone is used to tailor the size, as well as the permeability of the resultant capsules. Furthermore, microencapsulation of fluorescently labeled macromolecules (20-2000 KDa) is demonstrated. The permeability of the capsules is observed to be stimuli responsive, making it possible to incorporate a pH-triggered payload release from the capsules. The relatively simple preparation of capsules with controlled dimensions and tunable permeability, alongside the biocompatibility and biodegradability of both polymer components makes these promising materials for potential use in smart drug-delivery systems.

Ansoft HFSS Software Application for the Dielectric and Magnetic Measurements of Ferroelectrics and Related Materials in Microwaves

One of the basic problems in measurements of the electrical properties of materials is finding relations between measured electrical values and characteristics of the material, especially when the shape of a sample is complex. Electromagnetic (EM) simulation software calculates electrical parameters of defined structure. However, at measurements, it is necessary to solve a reverse problem, for what the software is not adapted. Using some properties of the program it is possible to find the solution of the reverse problem. Also it allows to take into account the spurious factors arising at connection of a measured sample to a measuring circuit. The method being discussed was tested by calculation of complex dielectric permittivity of Bi1.5ZnNb1.5O7-xF2 (BZN) pyrochlore ceramics as well as calculation of both complex dielectric permittivity and complex dielectric permeability of carbon-coated capsules of Ni (Ni@C) embedded into polyurethane matrix from experimental results.

Microencapsulation and chondrogenic differentiation of human mesenchymal progenitor cells from subchondral bone marrow in Ca-alginate for cell injection

The application of stem cells is a promising therapeutic approach for cartilage regeneration. For cell therapies, a biocompatible injectable carrier, which improves retention and cell distribution and enables cell differentiation, is a prerequisite. In this study, Ca-alginate microcapsules containing human subchondral cortico-spongious progenitor cells were prepared and the chondrogenic differentiation potential was verified by real-time reverse transcription-polymerase chain reaction analysis of typical chondrogenic marker genes. The results confirmed that these cells were able to differentiate along the chondrogenic lineage when encapsulated in Ca-alginate microcapsules with a mean diameter of 600–700 μm and stimulated with TGF-beta3. Chondrogenic marker genes type II collagen, aggrecan and cartilage oligomeric matrix protein were induced together with type I collagen, whereas adipogenic and osteogenic marker genes showed no induction over 14 days. After 28 days, proteoglycans and type II collagen were evident histochemically and immunohistochemically. Mechanical stability as well as permeability of Ca-alginate capsules were analysed over the course of cultivation and found to be qualified for stable cell immobilization and sufficient exchange of solutes. Therefore, from the cell biology point of view, Ca-alginate, an established hydrogel scaffold material is suited for regenerative therapies of cartilage defects based on the injection of progenitor cells.

Tuning swelling pH and permeability of hydrogel multilayer capsules.

We report on tuning swelling pH transitions of hydrogel hollow capsules that were derived from hydrogen-bonded multilayers via chemical cross-linking. The capsules were either of a single component - a weak poly(carboxylic acid), such as poly(acrylic acid) (PAA), poly(methacrylic acid) (PMAA), or poly(ethacrylic acid) (PEAA) - or contained two hydrogen-bonding polymers, such as in poly(carboxylic acid)/poly(N-vinylpyrrolidone-co-NH2) (PVPON-co-NH2) or in poly(carboxylic acid)/poly(N-vinylcaprolactam-co-NH2) (PVCL-co-NH2) systems. By varying the acidity of weak polyelectrolytes, the capsule swelling can be tuned over a wide pH range from 5 to 10. We show that differently from one-component capsules, the swelling amplitude of two-component capsules is limited by the number of cross-links provided by amino-containing units of a PVCL-co-NH2 copolymer. For two-component capsules with the same degree of cross-linking, permeability at the minimum swelling pH was decreased for PMAA-neutral copolymer capsules as compared to those of PAA-neutral copolymer. We also demonstrate that swelling pH of one-component capsules in the acidic region can be modulated via reversible association with a polycation. The fine control over the swelling pH transitions and permeability of hydrogel capsules enables their use in biomedical applications.

Ultrasonically Induced Opening of Polyelectrolyte Microcontainers

The effect of ultrasonic treatments of different intensity and duration on the integrity and permeability of polyelectrolyte capsules was investigated both in poly(allylamine)/poly(styrene sulfonate) and Fe(3)O(4)/poly(allylamine)/poly(styrene sulfonate) polyelectrolyte capsules. Ultrasonic treatment of polyelectrolyte capsules induces the destruction of the polyelectrolyte shell and the release of the encapsulated material even at short (5 s) sonification times. The presence of magnetite nanoparticles significantly improves the efficiency of the ultrasonically stimulated release of the encapsulated compounds and enables magnetically controlled delivery to the desired site before ultrasonic treatment. Release of the encapsulated compound induced at ultrasonic power comparable to those of ultrasonic generators applied in medicine, demonstrating practical application of the ultrasonically triggered capsule opening in medicine.

Otago Glaucoma Surgery Outcome Study: Cytology and Immunohistochemical Staining of Bleb Capsules around Molteno Implants

To describe the cytology and immunohistochemistry of Molteno implant capsules from cases of primary and secondary glaucoma. Histologic features of capsules including cell cytology, the distribution of activated (proliferating) cells, apoptosing cells, and membrane bound vesicles (presumed death messengers) were assessed by light microscopy and correlated with clinicopathological features in 10 noninflamed eyes with good intraocular pressure control (nine autopsy and one enucleation) obtained from 2 months to 16.8 years after insertion of Molteno implants. All bleb capsules demonstrated two distinct layers. The thin external layer was cellular with fairly numerous small blood vessels coursing through normally staining, regularly arranged collagen fibers. The thicker, deeper layer was avascular, relatively acellular, and characterized by regularly arranged swollen and fragmented collagen fibers. Most cells in the external layer appeared normal; however, between 5% (in recently formed blebs) and approximately 50% (in well established blebs) showed cytological and/or immunohistochemical changes characteristic of metabolic activation and/or apoptosis. All cells in the deeper layer, regardless of time after surgery, also demonstrated cytological and/or immunohistochemical staining characteristic of metabolic activation and/or apoptosis. In addition, the deeper layer evidenced large numbers of minute membrane-bound vesicles (presumed death messengers). The balance between activation and apoptosis regulates the thickness and permeability of bleb capsules, and the normal lifecycle of bleb capsules includes continual inner surface degeneration and external surface renewal.

The effect of selected parameters of formation on properties of alginate/Ca2+/oligochitosan capsules

Optimization of the technological parameters affecting the mechanical properties and permeability of capsules is essential to produce capsules with improved properties for cell immobilization. In the present paper, the effect of different parameters on the technological properties of alginate/Ca2+/oligochitosan capsules has been investigated. The correct adjustment of the alginate concentration in the polymer matrix and the oligochitosan molar mass, concentration and coating time, have been found to be key parameters in obtaining porous and mechanically stable alginate/Ca2+/oligochitosan capsules. Results showed that an increase in the coating time and concentration of the alginate generated more stable capsules with a reduced membrane cut-off. Furthermore, we have established some correlations between capsule properties and the effectiveness of chitosan binding within the capsule's membrane. Data addressed herein could be a valid tool to fabricate optimized alginate/Ca2+/oligochitosan capsules with a potential for use in cell immobilization technology. Copyright © 2006 Society of Chemical Industry

Controlled Permeability of Polyelectrolyte Capsules via Defined Annealing

The influence of thermal treatment on the permeability of polyelectrolyte multilayer capsules is studied via confocal fluorescence microscopy of individual microcapsules. For the specific most frequently used example, capsules made of poly(styrenesulfonic acid) and poly(allylamine hydrochloride), the penetration of fluorescein is shown to be reduced by 3 orders of magnitude on heating at 80 °C. The data show that holes formed during preparation may be annealed in a predictable way.

Permeability and stability of chitosan-based capsules: effect of preparation.

Capsules were obtained by interpolymer complexation between chitosan (polycation) and sodium hexametaphosphate (oligoanion). The effect of preparation variables such as the pH, ionic strength as well as the reagent and porogen concentration on the capsule characteristics was evaluated. By decreasing the chitosan/SMP ratio, adding mannitol up to 1% or maintaining the salt concentrations below 0.15 w/v%, the diffusion characteristics can be modulated without disturbing the capsule mechanical stability. Higher concentrations of the cross-linking agent (2.25 w/v%) produced stable capsules only in the absence of electrolyte and low polyol amounts. Furthermore, by increasing the ionic strength, or the pH of the initial chitosan solution, the membrane exclusion limit shifted to higher values concomitant with a significant loss in the membrane compression resistance. The results obtained showed that the capsule characteristics could be independently controlled by manipulating the coacervation conditions.

Capsule permeability via polymer and protein ingress/egress

Static incubation tests, where microcapsules and beads are contacted with polymer and protein solutions, have been developed for the characterization of permselective materials applied for bioartificial organs and drug delivery. A combination of polymer ingress, detected by size-exclusion chromatography, and protein ingress/egress, assessed by gel electrophoresis, provides information regarding the diffusion kinetics, molar mass cutoff (MMCO) and permeability. This represents an improvement over existing permeability measurements that are based on the diffusion of a single type of solute. Specifically, the permeability of capsules based on alginate, cellulose sulfate, polymethylene-co-guanidine were characterized as a function of membrane thickness. Solid alginate beads were also evaluated. The MMCO of these capsules was estimated to be between 80 and 90 kDa using polymers, and between 116–150 kDa with proteins. Apparently, the globular shape of the proteins (radius of gyration (Rg) of 4.2–4.6 nm) facilitates their passage through the membrane, comparatively to the polysaccharide coil conformation (Rg of 6.5–8.3 nm). An increase of the capsule membrane thickness reduced these values. The MMCO of the beads, which do not have a membrane limiting their permselective properties, was higher, between 110 and 200 kDa with dextrans, and between 150 and 220 kDa with proteins. Therefore, although the permeability estimated with biologically relevant molecules is generally higher due to their lower radius of gyration, both the MMCO of synthetic and natural water-soluble polymers correlate well, and can be used as in vitro metrics for the immune protection ability of microcapsules and microbeads. This article shows, to the authors' knowledge, the first reported concordance between permeability measures based on model natural and biological macromolecules. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 75: 1165–1175, 2000

Microencapsulated human hepatoma (HepG2) cells: capsule-to-capsule variations in protein secretion and permeability

Human hepatoma (HepG2) cells were microencapsulated in hydroxyethyl methacrylate-methyl methacrylate by an interfacial precipitation process. The secretion of a,-antitrypsin (AT: 52 kDa) and fibrinogen (Fbg: 340 kDa) from individual capsules was determined using sensitive enzyme-linked immunosorbent assays. A significant capsule-to-capsule variation in the secretion rates of both AT and Fbg was found. After 2 weeks of in vitro culture, ∼ 20 and 70% of the capsules did not secrete any detectable AT and Fbg, respectively. The relative secretion of Fbg with respect to AT (Fbg/AT) for those capsules which secreted AT also varied among the individual capsules: ∼50% of capsules had zero Fbg/AT, presumably indicating the fraction of the capsules exhibiting the expected sieving effect to the larger protein Fbg but not to the smaller protein AT. Using a new procedure for the permeability of individual capsules (horseradish peroxidase, 40 kDa, as the model protein), a significant capsule-to-capsule variation in protein permeability was found consistent with the observed variation in Fbg and AT release.

Assessment of the reproducibility of alginate encapsulation of pancreatic islets using the MTT colorimetric assay.

Radioisotope diffusion experiments demonstrate that alginate/polyaminoacid encapsulation can prevent antibody and cytotoxic cell contact in vitro. The unpredictable outcome of xenotransplantation of encapsulated islets may reflect incomplete encapsulation. We have assessed a cytotoxic/MTT (tetrazolium) assay to test antibody permeability of capsules. Samples of free porcine islet tissue, and islet tissue encapsulated in alginate/poly-L-lysine/alginate microspheres were incubated with fresh autologous pig serum or normal human serum overnight. Cell metabolism was assessed by the MTT assay. Data from eight experiments (10 replicates/experiment) were analyzed using the Mann-Whitney U-test. Values were deemed significant when p < 0.05. Free islets cultured in human serum showed a significant reduction in metabolism when compared with islets cultured in pig serum: percentage reduction 52 +/- 23% (mean +/- SD). The differences in formazan production were significant in all experiments (p < 0.05). Alginate encapsulation of islets or removal of xenoreactive antibodies in human serum by adsorption was shown to prevent the effects of complement-mediated lysis. However, in one of the eight experiments, there was a significant reduction in islet metabolism after exposure of encapsulated porcine islets to human serum. In conclusion, it has been shown that alginate encapsulation can prevent complement-mediated lysis. However, the encapsulation process employed was imperfect and did not prevent complement-mediated lysis of porcine islets in all experiments. The cytotoxicity/MTT assay allows investigation of the permeability of capsules to serum antibodies and could be performed to determine the viability of the islets and the integrity of microcapsules prior to transplantation.