Cross-linked Microcapsules Research Articles

Chia Oil Microencapsulation Using Tannic Acid and Soy Protein Isolate as Wall Materials.

The use of proteins to produce oil-containing microcapsules has been previously analyzed; however, their chemical modification, in order to improve their performance as wall materials, is a strategy that has not been widely developed yet. This study aimed to analyze the chemical modification of the proteins through cross-linking reactions with tannic acid and to evaluate their performance as wall materials to the microencapsulation of oils rich in polyunsaturated fatty acids. The cross-linking reaction of isolated soy protein and tannic acid was carried out at pH 10-11 and 60 °C. Subsequently, emulsions were made with a high-speed homogenizer and microcapsules were obtained by spray drying. Microcapsules were characterized by particle size, morphology (SEM), total pore area and % porosity (mercury intrusion methodology), superficial properties (contact angle), and size distribution of oil droplets (by laser diffraction). Additionally, encapsulation efficiency was determined as a function of total and surface oil. Oil chemical stability and quality were studied by Rancimat, hydroperoxide values, and fatty acid profiles. In addition, a storage test was performed for 180 days, and released oil and polyphenols were determined by in vitro gastric digestion. Moreover, the fatty acid composition of the oil and the total polyphenol content and antioxidant capacity of polyphenols were analyzed. The results showed that spray-dried microcapsules had an encapsulation efficiency between 54 and 78%. The oxidative stability exhibited a positive correlation between the amount of polyphenols used and the induction time, with a maximum of 27 h. The storage assay showed that the peroxide value was lower for those cross-linked microcapsules concerning control after 180 days. After the storage time, the omega-3 content was reduced by 49% for soy protein samples, while cross-linked microcapsules maintained the initial concentration. The in-vitro digestion assay showed a decrease in the amount of oil released from the cross-linked microcapsules and an increase in the amount of polyphenols and a higher antioxidant capacity for all samples (for example, 238.10 mgGAE/g and 554.22 mg TE/g for undigested microcapsules with TA 40% versus 322.09 mgGAE/g and 663.61 mg TE/g for digested samples). The microcapsules showed a high degree of protection of the encapsulated oil, providing a high content of polyunsaturated fatty acids (PUFAS) and polyphenols even in prolonged storage times.

Quinoa protein isolate-gum Arabic coacervates cross-linked with sodium tripolyphosphate: Characterization, environmental stability, and Sichuan pepper essential oil microencapsulation

Quinoa protein isolate-gum Arabic coacervates (QPI-GA coacervates) was cross-linked with sodium tripolyphosphate (STPP) to enhance their physicochemical properties. The optimum concentration of STPP for cross-linking was determined experimentally to be 0.2 g/g of QPI-GA mixture. After cross-linking, QPI-GA coacervates changed to the more ordered structure, and showed higher pH, ionic, and thermal stability. The STPP cross-linked coacervates were used as wall materials for Sichuan pepper essential oil (SPEO) encapsulation with encapsulation efficiency of 87.25 %. Compared with uncross-linked microcapsules, cross-linked microcapsules showed higher SPEO retention at high temperature, different pH, and high ionic concentration. Meanwhile, STPP cross-linked microcapsules improved the stability of SPEO during oral and gastric digestion as indicated by the lower SPEO release, which guaranteed the higher release and absorption in intestinal digestion of SPEO. Consequently, STPP cross-linked QPI-GA coacervates can be an ideal carrier for flavors or active ingredients, protecting them against harsh environment conditions during food processing and digestion.

Preparation and characterization of low-yellowing cross-linked shell microencapsulated phase change materials for latent thermal energy storage

A Cross-linked microencapsulated phase change material (MEPCM) was prepared using butyl stearate as the core material and isophorone diisocyanate (IPDI) and triethanolamine (TEA) as the reaction monomers, while a Linear MEPCM was prepared using 2,4-toluene diisocyanate (TDI) and diethylenetriamine (DETA) as the reaction monomers. The thermal stability, densification, chemical structure, phase change properties and surface morphology of the two types of microcapsules were characterized and analyzed, respectively, and the thermal storage properties and whiteness of the finished fabrics with the two microcapsules were measured. The results showed that the surface of the prepared Cross-linked MEPCMs was smooth and dense, with good wrapping effect and no leakage of core material, while the Linear microcapsules had serious leakage of core material and adhesion between particles; the thermal stability and denseness of the cross-linked microcapsules were significantly improved compared with the linear-shell microcapsules. After continuous drying at 120 °C for 6 h, the mass loss rate of cross-linked microcapsules was only 6.23%, while the mass loss rate of the linear microcapsules was up to 22.35%. The fabric finished with the cross-linked microcapsules had a great phase change properties and wash resistance, the whiteness was significantly higher than that of the linear microcapsules, had an obvious low yellowing characteristic. The prepared microcapsules had good prospects for textile applications.

Characterization of cross-linked chitosan by ionic and covalent crosslinking agents as wall material of red ginger oleoresin microcapsules

The aim of this study was to determine the characterization of ionic and covalent interactions to form a crosslinking network with chitosan as a wall material of microcapsules. Red ginger oleoresin microcapsule was prepared by emulsion crosslinking method. Red ginger oleoresin was mixed and stirred with chitosan solution to form an emulsion, then added to corn oil and stirred again to form a second emulsion. Crosslinking agents of glutaraldehyde saturated toluene (GST) or sodium tripolyphosphate (TPP) solution was slowly added to the emulsion. When using a crosslinking agent of TPP solution was added glacial acetic acid to adjust pH. Red ginger oleoresin microcapsules were filtered and washed with petroleum ether followed by n-hexane and then dried in an oven. Microcapsules from chitosan that are cross-linked with GST produce higher yield and size of microcapsules compared to TPP. Whereas, the highest encapsulation efficiency produced from chitosan cross-linked with TPP was 91.63±0.02%. Meanwhile, the highest cumulative release was obtained from TPP cross-linked chitosan microcapsules of 63.71% and the lowest was 50.01% from chitosan microcapsules that cross-linked with GST. The conclusion of this study was the differences between ionic and covalent crosslinking agents produce different microcapsule characteristics. Microcapsules from chitosan cross-linked with GST generated more compact with a smoother surface than with TPP.

Improving survivability of Lactobacillus plantarum in alginate-chitosan beads reinforced by Na-tripolyphosphate dual cross-linking

In the present study, Lactobacillus plantarum PTCC 1058 was microencapsulated in Alginate-chitosan blended beads based on ionically dual cross-linking by Na-tripolyphosphate (Na-TPP). The homogenous solution of bacteria and alginate was dripped into the gelling bath of calcium chloride. After 30 min hardening, filtrate beads were transferred into the solution of chitosan. Dual cross-linked gel beads were prepared by employing Na-TPP solution to the chitosan coated beads. Morphology, particle size, alginate-chitosan interaction, characterizing the structure of single and dual cross-linked beads were determined by using scanning electron microscopy SEM, FTIR and XRD analysis. FTIR analysis demonstrated fabrication of the Na-tripolyphosphate dual cross-linked microcapsules. X-ray diffractograms revealed less amorphous nature of Ag/Cs/TPP microcapsules compared to Ag/Cs ones. Survivability of probiotics and swelling behavior of microcapsules were also evaluated under simulated gastrointestinal conditions. Based on the results, the highest viability corresponds to the dual cross-linked beads (by only 1.58 ± 0.03 log reduction) compared to single cross-linked alginate (2.26 ± 0.09 log) and chitosan-coated alginate beads (1.78 ± 0.1 log). Thus, the reinforced microcapsules could be suitable for improving the capsule stability in site-specific delivery applications.

Development and <i>in vitro</i> characterization of 5-flurouracilloaded, colon-targeted drug delivery system

Purpose: To prepare chondroitin sulphate–polyvinyl alcohol cross-linked microcapsules (miCAPs) for controlled delivery of 5-flurouracil (5-FU) in cancer patients.Method: Nine different miCAP formulations were prepared using emulsion cross-linking procedure. The formulations were evaluated for their physicochemical properties, complex formation, stability at variable temperatures, safety, as well as drug-loading and drug-release characteristics. The effects of glutaraldehyde (GA), polymer concentration and stirring speed on 5-FU release at various pH were also assessed.Results: One of the miCAP formulations (miCAP-1) was adjudged the most suitable based on its particle size, high drug loading (75.3 %, p = 0.034), and high entrapment efficiency (85.2 %, p = 0.031). Best-fit drug release model was Higuchi model based on regression coefficient value (R2) while drug release mechanism was Fickian.Conclusion: Highly stable, crosslinked, amorphous and drug delivery system has been successfully developed. The delivery system is potentially suitable for acid-sensitive therapeutic moieties and where controlled release is desired.Keywords: Emulsion cross-linking, Colon-specific delivery, 5-Flurouracil, Glutaraldehyde, Kinetic models

Tunable Permeability of Cross-Linked Microcapsules from pH-Responsive Amphiphilic Diblock Copolymers: A Dissipative Particle Dynamics Study.

Using dissipative particle dynamics simulation, we probe the tunable permeability of cross-linked microcapsules made from pH-sensitive diblock copolymers poly(ethylene oxide)-b-poly(N,N-diethylamino-2-ethyl methacrylate) (PEO-b-PDEAEMA). We first examine the self-assembly of non-cross-linked microcapsules and their pH-responsive collapse and then explore the effects of cross-linking and block interaction on the swelling or deswelling of cross-linked microcapsules. Our results reveal a preferential loading of hydrophobic dicyclopentadiene (DCPD) molecules in PEO-b-PDEAEMA copolymers. Upon reduction of pH, non-cross-linked microcapsules fully decompose into small wormlike clusters as a result of large self-repulsions of protonated copolymers. With increasing degree of cross-linking, the morphology of the microcapsule becomes more stable to pH change. The highly cross-linked microcapsule shell undergoes significant local polymer rearrangement in acidic solution, which eliminates the amphiphilicility and therefore enlarges the permeability of the shell. The responsive cross-linked shell experiences a disperse-to-buckle configurational transition upon reduction of pH, which is effective for the steady or pulsatile regulation of shell permeability. The swelling rate of the cross-linked shell is dependent on both electrostatic and nonelectrostatic interactions between the pH-sensitive groups as well as the other groups. Our study highlights the combination of cross-linking structure and block interactions in stabilizing microcapsules and tuning their selective permeability.

Exploiting Salt Induced Microphase Separation To Form Soy Protein Microcapsules or Microgels in Aqueous Solution.

Self-assembly of native glycinin at room temperature was investigated as a function of the pH and the NaCl concentration. Microphase separation leading to the formation of dense protein microdomains was observed by confocal laser scanning microscopy. Depending on the conditions, the microdomains coalesced into a continuous protein rich phase or associated into large clusters. Addition of β-conglycinin inhibited phase separation and reduced the pH range in which it occurred. Microdomains of glycinin that were formed in the presence of 0.1 M NaCl transformed into hollow stable cross-linked microcapsules when heated above 60 °C with diameters between 3 and 30 μm depending on the protein concentration and a shell thickness between 1.0 and 1.4 μm. The microcapsules were stable to dilution in salt free water, whereas microdomains formed at room temperature redispersed. Microdomains formed in mixtures with β-conglycinin did not transform into microcapsules, but they became stable cross-linked homogeneous microgels.

Microfungal spores (Ustilago maydis and U. digitariae) immobilised chitosan microcapsules for heavy metal removal

Designing effective chitosan-based biosorbents from unexploited biomass for heavy metal removal has received much attention over the past decade. Ustilago, loose smut, is a ubiquitous fungal plant pathogen infecting over 4000 species including maize and weed. This study aimed to establish whether the spores of the phytopathogenic microfungi Ustilago spores can be immobilised in cross-linked chitosan matrix, and it reports findings on heavy metal sorption performance of chitosan/Ustilago composite microcapsules. Immobilisation of Ustilago maydis and U. digitariae spores (from maize and weed) in chitosan microcapsules was achieved via glutaraldehyde cross-linking. The cross-linked microcapsules were characterised using scanning electron microscopy, FT-IR spectroscopy and thermogravimetric analysis. Sorption capacities of chitosan-U. maydis and chitosan-U. digitariae microcapsules were investigated and compared to cross-linked chitosan beads: Cu(II): 66.72, 69.26, 42.57; Cd(II): 49.46, 53.96, 7.87; Cr(III): 35.88, 49.40, 43.68; Ni(II): 41.67, 33.46, 16.43 and Zn(II): 30.73, 60.81, 15.04mg/g, respectively. Sorption experiments were conducted as a function of initial metal ion concentration (2–10mg/L), contact time (60–480min), temperature (25, 35 and 45°C), amount of the sorbent (0.05–0.25g) and pH of the metal solution. The microcapsules with spores exhibited better performance over the plain chitosan beads, demonstrating their potential use in water treatment.

Dual Cross-Linked Carboxymethyl Sago Pulp-Gelatine Complex Coacervates for Sustained Drug Delivery

In the present work, we report for the first time the complex coacervation of carboxymethyl sago pulp (CMSP) with gelatine for sustained drug delivery. Toluene saturated with glutaraldehyde and aqueous aluminum chloride was employed as cross-linkers. Measurements of zeta potential confirm neutralization of two oppositely charged colloids due to complexation, which was further supported by infrared spectroscopy. The coacervates encapsulated a model drug ibuprofen and formed microcapsules with a loading of 29%–56% w/w and an entrapment efficiency of 85%–93% w/w. Fresh coacervates loaded with drug had an average diameter of 10.8 ± 1.93 µm (n = 3 ± s.d.). The coacervates could encapsulate only the micronized form of ibuprofen in the absence of surfactant. Analysis through an optical microscope evidenced the encapsulation of the drug in wet spherical coacervates. Scanning electron microscopy revealed the non-spherical geometry and surface roughness of dried drug-loaded microcapsules. X-ray diffraction, differential scanning calorimetry and thermal analysis confirmed intact and crystalline ibuprofen in the coacervates. Gas chromatography indicated the absence of residual glutaraldehyde in the microcapsules. Dual cross-linked microcapsules exhibited a slower release than mono-cross-linked microcapsules and could sustain the drug release over the period of 6 h following Fickian diffusion.

Preparation of macroporous poly(N-isopropylacrylamide) hydrogels using a suspension–gelation method

A macroporous hydrogel, consisting of a homogeneous cross-linked polymer network and linear polymers containing randomly distributed sphere-like cavities, was developed using a suspension–gelation method. This method involves the synthesis of composite hydrogels containing distributed microcapsules as a pore template (porogen) by free radical polymerization, followed by a chemical treatment to break down the structure of the microcapsules within the hydrogels. Macroporous hydrogels were successfully synthesized in a model system consisting of thermosensitive N-isopropylacrylamide hydrogels and physically cross-linked microcapsules of calcium alginate, which were prepared using an electrostatic atomization method. Observation of the internal structure of the hydrogels using scanning electron microscopy revealed that the composite hydrogels contain microcapsules and the macroporous hydrogels have non-interconnected macropores created by the microcapsules as the template. The thermosensitive swelling properties and the mechanical properties of the hydrogels were characterized.

Chitosan nanoparticles as particular emulsifier for preparation of novel pH-responsive Pickering emulsions and PLGA microcapsules

In this work, we describe a novel and simple method for fabricating biocompatible microcapsules. Chitosan colloidal nanoparticle-coated micrometer-sized poly(lactic-co-glycolic acid) (PLGA) microcapsules were fabricated via a combined system of “Pickering-type” emulsion route and solvent volatilization method in the absence of any molecular surfactants. Stable oil-in-water emulsions were prepared using chitosan colloidal nanoparticles as a particulate emulsifier and a dichloromethane (CH2Cl2) solution of PLGA as an oil phase. Moreover, this stable emulsion present a good pH-responsive characteristic. The uncross-linked chitosan nanoparticles coated PLGA microcapsules were fabricated by the evaporation of CH2Cl2 from the emulsion, and the cross-linked chitosan nanoparticles coated PLGA microcapsules were prepared by cross-linking with glutaraldehyde and evaporation of CH2Cl2. The two types of microcapsules were characterized in terms of size, morphology using scanning electronic microscope (SEM), optical microscope, and so on. These observations confirm the robust nature of these cross-linked microcapsules. Moreover, a possible mechanism for the formation of these microcapsules was proposed. The combined system of Pickering emulsion and solvent volatilization opens up a new route to fabricate a variety of microcapsules.

Interpenetrating polymer network microcapsules of gellan gum and egg albumin entrapped with diltiazem–resin complex for controlled release application

Diltiazem HCl, a water soluble drug was bound to Indion 254 ®, a cation exchange resin and resulting drug–resin complex was entrapped within interpenetrating polymer network (IPN) microcapsules of gellan gum and egg albumin prepared by ionotropic gelation and covalent crosslinking method. The IPN microcapsules were characterized by SEM, DSC, TGA, XRD and FTIR analyses. The pure drug diltiazem showed rapid and complete dissolution within 60 min, while drug release from drug-resinate was extended for 3 h and that from IPN microcapsules was still slower. The ionically cross-linked microcapsules were capable of releasing drug up to 9 h, and that from dual crosslinked microcapsules was extended up to 15 h. The microcapsules which were prepared with higher concentration of glutaraldehyde released the drug more slowly. The release data were fitted to an empirical equation to determine the transport mechanism.

Cross-Linked Microcapsules Formed From Self-Deactivating Reactive Polyelectrolytes

Poly(methyl vinyl ether-alt-maleic anhydride) (PMM(0)) was partially hydrolyzed in a 9/1 acetonitrile-d(3)/D(2)O mixture and then diluted with an aqueous buffer and coated onto poly-L-lysine (PLL)-coated calcium alginate capsules. The resulting 50% hydrolyzed polymer (PMM(50)) is bound to the surface-immobilized PLL through both electrostatic and covalent interactions, resulting in a shell-cross-linked hydrogel capsule that is resistant to chemical challenges. Further hydrolysis of PMM(50) in aqueous buffer was monitored by potentiometry and was found to proceed with a half-life time of about 2.5 min at 20 degrees C such that residual anhydride groups not consumed by cross-linking with PLL would be deactivated by hydrolysis within several minutes of shell formation, removing potential sites for undesired protein binding. Initial protein-binding tests involving incubation of the capsules in bovine serum albumin solutions for 24 h showed no indication of protein binding. The effects of coating temperature, PLL concentration and molecular weight, PMM(50) molecular weight, and multiple PLL-PMM(50) coatings on shell morphology and behavior were studied using confocal fluorescence microscopy as well as chemical challenges involving sodium citrate and sodium hydroxide. The resilience of the cross-linked shell improved with increasing concentrations of PLL and decreasing molecular weight of PMM(50), both of which resulted in more polyelectrolyte being bound to the capsule. The permeability of these covalently cross-linked capsules was studied using fluorescently labeled dextrans and was found to be comparable to standard calcium alginate-PLL-alginate (APA) capsules.

Formation and Size Tuning of Colloidal Microcapsules via Host−Guest Molecular Recognition at the Liquid−Liquid Interface

Stimuli-responsive colloidal microcapsules have been fabricated at the oil-water interface using molecular recognition between functionalized gold nanoparticles. Water-soluble beta-cyclodextrin-capped gold nanoparticles and organo-soluble adamantyl-functionalized gold nanoparticles are self-assembled at the water-toluene interface via specific host-guest molecular interactions to provide robust microcapsules. Multivalent interactions of complementary ligands on the nanoparticle surface provide stability to these capsules. Unlike covalently cross-linked microcapsules, the reversible nature of these bridging interactions can be used to manipulate the size of these capsules via introduction of competing adamantane containing amphiphilic guest molecules. Partial disruption of interfacial cross-linking allows microcapsules to coalesce with each other to form larger capsules.

Alginate-based microencapsulation of retinal pigment epithelial cell line for cell therapy

The goals of this study were to evaluate human retinal pigment epithelial cell line (ARPE-19) for cell encapsulation and to optimize the alginate-based microencapsulation. We used immortalized ARPE-19 cells and the transfected sub-line that expresses secreted alkaline phosphatase (SEAP) reporter enzyme. Alginate was cross-linked with different divalent cations (Ca 2+, Ba 2+, Sr 2+ and combination of Ca 2+ and Ba 2+), coated first with poly- l-lysine (PLL), and then with alginate. Microcapsules with different pore sizes and stability were generated. The pore size of the microcapsules was assessed by the release of encapsulated fluorescein isothiocyanate (FITC)-dextrans. The viability of the cells in the microcapsules was studied in vitro by assessing the secretion rates of SEAP and oxygen consumption by the cells. The best microcapsule morphology, durability and cellular viability were obtained with alginate microcapsules that were cross-linked with Ca 2+ and Ba 2+ ions and then coated with PLL and alginate. Based on FITC-dextran release these microcapsules have porous wall that enables the rapid contents release. The ARPE-19 cells maintained viability in the Ca 2+ and Ba 2+ cross-linked microcapsules for at least 110 days. The alginate microcapsules cross-linked with Ca 2+ and Ba 2+ have sufficiently large pore size for prolonged cell viability and for the release of secreted SEAP model protein (Mw 50 kDa; radius of gyration of 3 nm). ARPE-19 cells show long-term viability and protein secretion within alginate microcapsules cross-linked with Ca 2+ and Ba 2+. This combination may be useful in cell therapy.

Template Polymerization to Fabricate Hydrogen-Bonded Poly(acrylic acid)/Poly(vinylpyrrolidone) Hollow Microcapsules with a pH-Mediated Swelling−Deswelling Property

Hydrogen-bonded hollow microcapsules with a lightly cross-linked shell structure were fabricated by polymerization of acrylic acid in a solution containing surface-modified silica particles and poly(vinylpyrrolidone) and a subsequent core removal with HF. By further incorporating additional cross-linkers, a highly cross-linked shell structure was produced, which endows the microcapsules with better stability against large pH fluctuations. The hollow and intact microcapsules in both wet and dry states were characterized and confirmed by TEM, SEM, AFM, and CLSM. The chemical compositions of the microcapsules and hydrogen bonding in the shells were determined by elemental analysis and FTIR spectroscopy, respectively. The continuous shells of the lightly cross-linked microcapsules on the silica particles are composed of PVP and PAA with an equal molar ratio of AA to VP. Alkaline treatment cannot separate PVP from PAA, which demonstrates the strong interactions between PAA and PVP. The lightly cross-linked and highly cross-linked microcapsules could increase their sizes along with the pH increase, following a sigmoidal regime. The capsule swelling−shrinking process is completely reversible at high and low pH values, respectively.

Single Component Chitosan Hydrogel Microcapsule from a Layer-by-Layer Approach

Smart biomaterials have found broad applications in modern medical technologies.1 However, the development of smart hydrogels with rapid response, good biocompatibility, and controllable degradability is still a formidable challenge. Chitosan, a biodegradable, nontoxic, and renewable linear polysaccharide, has been considered for various biomedical and pharmaceutical applications.2,3 To these ends, microparticles of chitosan in hundreds of micrometers have been prepared in different ways, including coacervation/ precipitation, spray-drying, emulsion cross-linking, emulsiondroplet coalescence, reverse micellization, ionic gelation, and sieving method.3,4 Complexation between chitosan and oppositely charged polysaccharides in solution is another way to synthesize chitosan microparticles; however, this process often leads to the formation of fibers.5 A new strategy, the so-called “layer-by-layer (LbL) assembly”, has been used here to fabricate microcapsules from chitosan. This strategy, based on the electrostatic interaction between oppositely charged polyelectrolytes, was first introduced by Decher et al. to fabricate thin films on planar supports by alternate adsorption of polycation and polyanion.6 Because of its advantages of fine control of the compositions and the thickness of the capsules, the LbL method received more and more attention in recent years.7-9 It was extended to three-dimensional (3D) systems by Mohwald et al. to fabricate core-shell particles and hollow capsules by further removal of the sacrificial core.10 In previous works, we first extended the LbL method based on hydrogen and covalent bonding to 3D systems and synthesized hydrogen or covalent bonded capsules.11,12 Chitosan bears positive charges and is a polycation at low pH. It has been used widely to fabricate LbL films13-19 and capsules20-22 with other polyelectrolytes. For the normal LbL methods, the capsule wall has at least two compositions. In certain applications, one may take advantage of the feasibility of several components by combining their individual material properties. On the other hand, the presence of a second polymer component for LbL assembling may limit the specific functionality of materials. For instance, the biocompatibility and biodegradability of chitosan could be destroyed by a second polymer component. Moya et al. fabricated a nearly single component capsule of polyallylamine hydrochloride (PAH) from the polystyrene sulfonate (PSS)/PAH LbL assembly by using cells as the template.23 The PAH in the capsule wall was oxidized and cross-linked, and then most of PSS was removed while removing the cell core template with sodium hypochlorite. However, this strategy could not be a general method for fabrication of single component capsules. Zhang et al. reported the preparation of single component 2-dimensional films from hydrogen-bonded LbL films, but these films were not cross-linked.24,25 Our new strategy is to selectively crosslink the chitosan chains and remove the second polymer component that was built up in the capsule walls (see Scheme 1). Using this strategy, single component chitosan hydrogel microcapsules were successfully synthesized. The pHresponsive volume phase transition of the chitosan hydrogel microcapsules could be controlled through the cross-linking density. The resultant chitosan gel microcapsules are nearly monodispersed, and the shell thickness is tunable, which is a big advantage to control the releasing kinetics of encapsulated drug or other molecules in response to pH or salt concentration changes. More importantly, although many shell cross-linked capsules have been made from synthetic block copolymers through a strategy of self-assembly of block copolymers with selective cross-linking on the shell block,26-31 it is very challenging, if not impossible, to synthesize well-defined block copolymers from natural polysaccharides. Our novel strategy here can provide a general method to synthesize shell cross-linked microcapsules from natural polysaccharides that have many applications in the pharmaceutical and medical field due to their biocompatibility and degradability.

Membrane formation mechanism of cross-linked polyurea microcapsules by phase separation method

This research was conducted to clarify the membrane formation mechanism of cross-linked polyurea microcapsules by phase separation method, especially the role of polymeric surfactant, such as poly(ethylene-alt-maleic anhydride) (poly(E-MA)) at the interface of O/W emulsion. It was found that poly(E-MA) was necessary for the formation of cross-linked polyurea membrane. The addition of sodium dodecyl sulphate (SDS) prohibited the membrane formation reaction at the interface, even in the case of poly(E-MA) concentration enough for polymeric microcapsule formation. From the results in this study, poly(E-MA) was found to be adsorbed on the O/W emulsion and provide the reaction site for the membrane formation of polymeric microcapsules.

Cross-linking properties of alginate gels determined by using advanced NMR imaging and Cu(2+) as contrast agent.

The entrapment of enzymes, drugs, cells or tissue fragments in alginates cross-linked with Ca(2+) or Ba(2+) has great potential in basic research, biotechnology and medicine. The swelling properties and, in turn, the mechanical stability are key factors in designing an optimally cross-linked hydrogel matrix. These parameters depend critically on the cross-linking process and seemingly minor modifications in manufacture have a large impact. Thus, sensitive and non-invasive tools are required to determine the spatial homogeneity and efficacy of the cross-linking process. Here, we show for alginate microcapsules (between 400 microm and 600 microm in diameter) that advanced (1)H NMR imaging, along with paramagnetic Cu(2+) as contrast agent, can be used to validate the cross-linking process. Two- and three-dimensional images and maps of the spin-lattice relaxation time T(1) of Ba(2+) cross-linked microcapsules exposed to external Cu(2+) yielded qualitative as well as quantitative information about the accumulation of Cu(2+) within and removal from microcapsules upon washing with Cu(2+) free saline solution. The use of Cu(2+) (having a slightly higher affinity constant to alginate than Ba(2+)) for gelling gave a complementary insight into the spatial homogeneity of the cross-linking process together with information about the mechanical stability of the microcapsules. The potential of this technique was demonstrated for alginates extracted from two different algal sources and cross-linked either externally by the conventional air-jet dropping method or internally by the "crystal gun" method.