Multilayer Microcapsules Research Articles

Multilayer composite microcapsules synthesized by Pickering emulsion templates and their application in self-healing coating

Multilayer composite microcapsules with IPDI prepared from lignin-stabilized Pickering emulsions were used for self-healing epoxy coatings.

Layered polymeric capsules inhibiting the activity of RNases for intracellular delivery of messenger RNA.

Intracellular delivery of messenger RNA (mRNA) is a promising approach for experimental and therapeutic manipulation of cellular activity. However, environmental RNase hinders reliable handling of mRNA for experimental and therapeutic use. In this study, biodegradable capsules composed of dextran sulfate and poly-l-arginine in the layer-by-layer (LbL) fashion are employed for the protection and delivery of mRNA. Our results demonstrate that addition of RNase inhibitors to mRNA while co-precipitation with CaCO3 and subsequent LbL encapsulation are both crucial to preserve the integrity of mRNA. The expression of functional luciferase enzyme in HEK293T human embryonic kidney cells after incubation with synthetic luciferase-encoding mRNA capsules indicates the reliability of the encapsulating system and cellular intake of functional mRNAs. These improvements in mRNA encapsulation should provide essential basis for microcapsule-based mRNA delivery for further applications.

Motion-based, high-yielding, and fast separation of different charged organics in water.

We report a self-propelled Janus silica micromotor as a motion-based analytical method for achieving fast target separation of polyelectrolyte microcapsules, enriching different charged organics with low molecular weights in water. The self-propelled Janus silica micromotor catalytically decomposes a hydrogen peroxide fuel and moves along the direction of the catalyst face at a speed of 126.3 μm s(-1) . Biotin-functionalized Janus micromotors can specifically capture and rapidly transport streptavidin-modified polyelectrolyte multilayer capsules, which could effectively enrich and separate different charged organics in water. The interior of the polyelectrolyte multilayer microcapsules were filled with a strong charged polyelectrolyte, and thus a Donnan equilibrium is favorable between the inner solution within the capsules and the bulk solution to entrap oppositely charged organics in water. The integration of these self-propelled Janus silica micromotors and polyelectrolyte multilayer capsules into a lab-on-chip device that enables the separation and analysis of charged organics could be attractive for a diverse range of applications.

Hierarchically organization of biomineralized alginate beads for dual stimuli-responsive drug delivery

Compartmentalized biomineralized alginate beads ranging from the micro to the visible scales with thermal- and pH-responsive drug delivery properties have been prepared via a one-step method in the present paper. Hollow multilayer microcapsules made of aliphatic poly(urethane-amine) (PUA) and sodium poly(styrenesulfonate) (PSS) serve as drug container to slow down the drug release. The results indicate that internal hollow multilayer microcapsules could hinder the permeation of the encapsulated Vitamin B2 (VB2) and retard the initial burst release of VB2. In addition, the drug release of compartmentalized biomineralized alginate beads exhibit distinguished pH- and thermal-dependent property due to pH-responsive alginate and the thermal-responsive aliphatic PUA. The drug release decreases when decreasing the pH value because the compact construction of alginate and biomineralized layer could prevent VB2 release from the beads. Moreover, the drug release is higher at 55°C than that at 37°C for the sake of the shrinkage of aliphatic PUA above its lower critical solution temperature (LCST). The results demonstrate that the compartmentalized biomineralized alginate beads show great potential as smart materials for controllable drug delivery.

Layer-by-layer assembled thin films and microcapsules of nanocrystalline cellulose for hydrophobic drug delivery.

A layer-by-layer (LbL) approach has been employed for the fabrication of multilayer thin films and microcapsules having nanofibrous morphology using nanocrystalline cellulose (NCC) as one of the components of the assembly. The applicability of these nanoassemblies as drug delivery carriers has been explored by the loading of an anticancer drug, doxorubicin hydrochloride, and a water-insoluble drug, curcumin. Doxorubicin hydrochloride, having a good water solubility, is postloaded in the assembly. In the case of curcumin, which is very hydrophobic and has limited solubility in water, a stable dispersion is prepared via noncovalent interaction with NCC prior to incorporation in the LbL assembly. The interaction of various other lipophilic drugs with NCC was analyzed theoretically by molecular docking in consideration of NCC as a general carrier for hydrophobic drugs.

Chitosan/dextran multilayer microcapsules for polyphenol co-delivery.

Polysaccharide-based nanostructured polymeric microcapsules were fabricated by the electrostatic layer-by-layer self-assembly technique and used to encapsulate mixtures of four different polyphenols in order to achieve their controlled release. The real-time fabrication of the dextran/chitosan multilayer was monitored by quartz crystal microbalance with dissipation monitoring, and the morphology of the nanostructured polymeric capsules was characterized by scanning electron microscopy. The polyphenol encapsulation was obtained by reversible permeability variation of the capsule shell in ethanol:water mixtures. The loading efficiency in different water:ethanol mixtures and the release rate in acidic conditions were characterized by UV spectroscopy and HPLC. The higher loading efficiency was obtained with an ethanol:water 35:65 phenolic solution, equal to 42.0±0.6%, with a total release of 11.5±0.7 mg of total polyphenols per 11.3 μL of microcapsules after 240 min of incubation in acidic environment. The results suggest that polysaccharide-based capsules can be successfully used to encapsulate and release low water-soluble molecules, such as polyphenols.

Highly magneto-responsive multilayer microcapsules for controlled release of insulin

In this study, magneto-responsive polyelectrolyte multilayer microcapsules were successfully prepared by the formation of shell with biocompatible iron oxide nanoparticles (Fe3O4 NPs) and polyallylamine hydrochloride (PAH) by layer-by-layer (LbL) self-assembly technique. The self-assembled microcapsules were characterized by SEM, TEM and zeta-potential analyzer. According to the pH sensitivity of the microcapsule membrane permeability, insulin was encapsulated, with the encapsulation efficiency of 92.08±5.57%. The in vitro release behavior in an external alternating magnetic field indicated that once the magnetic field was applied, the drug release was greatly accelerated. In addition, according to the observed pulse release upon cyclic on-off operations of magnetic field, it could be assumed that the magneto-responsive microcapsules had an excellent “switching on” effect, which might be attributed to the rearrangement of shell structure caused by magnetic nanoparticles twisting and polyelectrolyte chains shaking, hence the increase of microcapsule membrane permeability and the enhancement of insulin release.

Suitability of Using Monolayered and Multilayered Emulsions for Microencapsulation of ω-3 Fatty Acids by Spray Drying: Effect of Storage at Different Temperatures

Microencapsulation of ω-3 fatty acids by spray drying was studied using both monolayered (lecithin) and multilayered (lecithin-chitosan) fish oil emulsions with maltodextrin as wall material. Stability of the multilayered emulsions was higher than the monolayered ones, and increased with the increase of the concentration of chitosan. No differences were detected in the moisture or MY of the microcapsules related to the different composition of the corresponding emulsions. On the contrary, MEE was significant higher in the case of the microcapsules produced with the multilayered emulsions with the highest concentration of chitosan (1 % w/w), being related with lower detection of TBARS at high storage temperatures. Overall, this study shows the suitability of microencapsulating ω-3 fatty acids by spray drying using both monolayered and multilayered fish oil emulsions with maltodextrin as wall material. Multilayered microcapsules prepared with lecithin-chitosan emulsions provide a great protective effect against lipid oxidation of fish oil during storage at moderate to high temperatures (30 °C and 60 °C). These multilayered microcapsules could be therefore successfully used as a fish oil protection approach for storage before its use as an ingredient in food products.

Development of multilayer microcapsules by a phase coacervation method based on ionic interactions for textile applications.

The present study describes the development of multilayer microcapsules by 11 alternate additions of chitosan (Chi) and sodium dodecyl sulfate (SDS) in a combined emulsification and phase coacervation method based on ionic interactions. After an alkali treatment, microcapsules are applied on polyester (PET) fabric by a padding process to investigate their wash-durability on fabric. Air atmospheric plasma treatment is performed on PET fabric to modify the surface properties of the textiles. Zeta potential, X-ray photoelectron spectroscopy (XPS), wetting measurements, scanning electron microscopy (SEM), and atomic force microscopy (AFM) with surface roughness measurements are realized to characterize and determine wash durability of microcapsule samples onto PET. After alkali treatment, the microcapsules are selected for textile application because they are submicron sized with the desired morphology. The results obtained from various characterization techniques indicate that microcapsules are wash-durable on PET fabric pre activated by air plasma atmospheric as Chi based microcapsules can interact directly with PET by ionic interactions.

Islet function within a multilayer microcapsule and efficacy of angiogenic protein delivery in an omentum pouch graft

Abstract. We have previously described a new multilayer alginate microcapsule system, and the goals of the present study were to assess the in vitro function of islets encapsulated in its inner layer, and the angiogenic ability of FGF-1 delivered from the external layer in an omentum pouch. Following isolation and culture, islets were encapsulated in the inner core of microspheres (500 - 600 μm in diameter) with a semi-permeable poly-L-ornithine (PLO) membrane separating two alginate layers, and both unencapsulated and encapsulated islet function was assessed by a dynamic glucose perifusion. For angiogenesis experiments, one group of microcapsules without FGF-1 (control) and another (test) containing FGF-1 with heparin encapsulated in the external layer were made. One hundred microcapsules of each group were transplanted in Lewis rats ( n = 5/group) and were retrieved after 14 days for assessment of angiogenesis. Glucose perifusion of unencapsulated and encapsulated islets resulted in similar stimulation indices. The release of FGF-1 resulted in increased vascular density compared to controls. In conclusion, islets encapsulated in the core of multilayer alginate microcapsules maintain functionality and the microcapsule’s external layer is effective in delivery of FGF-1 to enhance graft neovascularization in a retrievable omentum pouch.

Cellular uptake of multilayered capsules produced with natural and genetically engineered biomimetic macromolecules

Multilayered microcapsules of chitosan and biomimetic elastin-like recombinamers (ELRs) were prepared envisaging the intracellular delivery of active agents. Two ELRs containing either a bioactive RGD sequence or a scrambled non-functional RDG were used to construct two types of functionalized polymeric microcapsules, both of spherical shape ∼4μm in diameter. Cell viability studies with human mesenchymal stem cells (hMSCs) were performed using microcapsule/cell ratios between 5:1 and 100:1. After 3 and 72h of co-incubation, no signs of cytotoxicity were found, but cells incubated with RGD-functionalized microcapsules exhibited higher viability values than RDG cells. The internalization efficacy and bioavailability of encapsulated DQ-ovalbumin were assessed by monitoring the fluorescence changes in the cargo. The data show that surface functionalization did not significantly influence internalization by hMSCs, but the bioavailability of DQ-ovalbumin degraded faster when encapsulated within RGD-functionalized microcapsules. The microcapsules developed show promise for intracellular drug delivery with increased drug efficacy.

Encapsulation of EV71-specific IgY antibodies by multilayer polypeptide microcapsules and its sustained release for inhibiting enterovirus 71 replication

To save egg yolk immunoglobulin (IgY) from damage by protease digestion in oral delivery, IgY specific to enterovirus 71 (EV71) was loaded into polypeptide microcapsules by the method of layer-by-layer encapsulation. Porous CaCO3 particles doped with IgY were used as templates which were coated with multilayer poly (L-lysine) (PLL) and poly (L-glutamic acid) (PGA). Then, IgY-loaded polypeptide microcapsules were fabricated after the removal of CaCO3 templates. The alternating adsorption was confirmed by the zeta potential and the successful formation of a multilayer polypeptide (PLL/PGA) shell was visualized by SEM. The influence of the PLL/PGA layer numbers on the IgY sustained release performance was studied in simulated gastric fluid. IgY release could be accurately controlled by adjusting the layer number of the polypeptide shells and only 45% of the IgY was released from 5-bilayer microcapsules in the initial 2 hours. The biological activity of the encapsulated IgY was investigated both in vitro and in vivo. Encapsulated EV71-specific IgY remained highly active and capable of neutralizing EV71 after multilayer polypeptide encapsulation, which provided a promising method to protect EV71-specific IgY in the gastric environment and to specifically release IgY at the target intestinal site for the prevention and control of EV71 infectious diseases.

Facile fabrication of nanocomposite microcapsules by combining layer-by-layer self-assembly and Pickering emulsion templating

Nanocomposite multilayer microcapsules are prepared by layer-by-layer self-assembly based on Pickering emulsions.

Encapsulation and Release of Moxifloxacin Hydrochloride in Chitosan–Dextran Sulphate Microcapsules

In the present work, multilayer microcapsules of size 350 nm were prepared with layer-by-layer assembly of oppositely charged chitosan and dextran sulphate on silica template. The monodisperse silica particles (310 nm) with fine spherical shape were successfully synthesized by Stober's method. Dissolution of silica particles in HF leads to the formation of hollow capsules. The resulting capsules were found to be able to effectively load moxifloxacin hydrochloride in the interior of the capsules under modest conditions without addition of other reagents, as demonstrated by scanning electron microscopy. Parameters affecting loading and release such as pH and initial concentrations were investigated. Release studies were performed in in-vitro mode with a semi-automatic release protocol, with different pH solutions in water and phosphate buffered saline. The size of silica particles was analysed by dynamic light scattering method. Scanning electron microscopy and energy dispersive X-ray spectroscopy measurements proved the surface morphology and purity of the hollow capsules from the core material. The kinetics of drug release mechanism was studied using Peppas and Higuchi models.

Fabrication of Red‐Blood‐Cell‐Like Polyelectrolyte Microcapsules and Their Deformation and Recovery Behavior Through a Microcapillary

Multilayer microcapsules with a biconcave discoidal shape mimicking red blood cells (RBCs) are fabricated. The structure of the RBC-like microcapsules is verified by scanning electron and confocal laser scanning microscopies. The capsules show elastic deformation after being forced through a microcapillary with a smaller diameter, exhibiting a high recovery ratio of ≈90%. When the capsules are coated with hemoglobin (Hb),they are able to reversibly bind and release oxygen.

Preparation and characterization of multilayered microcapsule-like microreactor for self-healing polymers

In this work, a multilayered microcapsule is proposed and prepared for use in self-healing polymers. Reactants for atom transfer radical polymerization (ATRP) are separately introduced into different places of the microcapsule to construct a latent ATRP reactor. When a polymer containing these capsules is damaged, crack induced breakage of the tiny vessels would lead to contact of the aforesaid reactants and hence autonomous polymerization of the released monomer, so that the damaged portions are re-bonded. The formation of the microcapsules goes through four steps. Optimum synthetic conditions for each step are carefully explored. The experimental results indicate that the components included in the multilayered microcapsules maintain their room temperature reactivity within the time of interest. The single microcapsule-type microreactor is provided with broad applicability as it can work alone with no need for additional chemicals and can be tailor-made according to the requirements of different polymers to be repaired.

Encapsulation of the Herbicide Picloram by Using Polyelectrolyte Biopolymers as Layer-by-Layer Materials

Microcapsules of the herbicide picloram (PLR) were formulated by a layer-by-layer (LbL) self-assembly method using the polyelectrolyte biopolymers of biocompatible chitosan (CS) and the UV-absorbent sodium lignosulfonate (SL) as shell materials. The herbicide PLR was recrystallized and characterized using XRD analysis. The obtained PLR-loaded microcapsules were characterized by using SEM, FTIR, CLSM, and ζ-potential measurements. The herbicide loading and encapsulation efficiency were also analyzed for the PLR-loaded microcapsules. The influence of LbL layer numbers on herbicide release and photodegradation rates was investigated in vitro. The results showed that the release rates and photodegradation rates of PLR in microcapsules decreased with increasing number of CS/SL self-assembly layers. The results demonstrated that polyelectrolyte biopolymer-based LbL multilayer microcapsules can be a promising approach for the controlled release of PLR as well as other pesticides with poor photostability or short half-release time.

Hollow Multilayer Microcapsules for pH‐/Thermally Responsive Drug Delivery using Aliphatic Poly(urethane‐amine) as Smart Component

Hollow multilayer microcapsules made of aliphatic poly(urethane-amine) (PUA) and sodium poly(styrene sulfonate) (PSS), templated on PSS-doped CaCO3 particles, are prepared for pH-/thermally responsive drug delivery. The electrostatic interaction and hydrogen bonding under weak-acid conditions between aliphatic PUA and PSS contribute to the formation of multilayer microcapsules. Scanning electron microscopy (SEM) results demonstrate an obvious variation of the hollow multilayer microcapsules in response to changes in temperature and pH value. Drug-release behaviors using DOX as a model drug demonstrate that the drug release increases on decreasing the pH value because of the interaction weakness between aliphatic PUA and PSS in acidic conditions. Moreover, the drug release is higher at 55 °C than that at 37 °C for the sake of the shrinkage of aliphatic PUA above its lower critical solution temperature (LCST).

Engineered multilayer ovarian tissue that secretes sex steroids and peptide hormones in response to gonadotropins

Although hormone replacement therapy is an option for the loss of ovarian function, hormone delivery through pharmacological means results in various clinical complications. The present study was designed to deliver sex steroids by a functional construct fabricated using encapsulation techniques. Theca and granulosa cells isolated from ovaries of 21-day old rats were encapsulated in multilayer alginate microcapsules to recapitulate the native follicular structure. Cells encapsulated in two other schemes were used as controls to assess the importance of the multilayer structure. The endocrine functions of the encapsulated cells were assessed in vitro for a period of 30 days. Encapsulated cells showed sustained viability during long-term in vitro culture with those encapsulated in multilayer capsules secreting significantly higher and sustained concentrations of 17 β-estradiol (E2) than the two other encapsulation schemes (p < 0.05, n = 6) in response to follicle-stimulating hormone (FSH) and luteinizing hormone (LH). In addition, cells in the multilayer microcapsules also secreted activin and inhibin in vitro. In contrast, when granulosa and theca cells were cultured in 2D culture, progesterone (P4) secretion increased while E2 secretion decreased over a 30-day period. In summary, we have designed a multilayer engineered ovarian tissue that secretes sex steroids and peptide hormones and responds to gonadotropins, thus demonstrating the ability to recapitulate native ovarian structure ex vivo.

Layer-by-Layer Assembled Polypeptide Capsules for Platinum-Based Pro-Drug Delivery

Platinum(IV), a pro-drug of platinum(II), was conjugated to poly(l-lysine) (PLL), and then assembled with poly(glutamic acid) (PGA) through a layer-by-layer (LbL) approach on colloidal silica templates. After removal of the templates, biodegradable PGA/PLL-Pt(IV) multilayer capsules (diameter = 0.5 μm) with 10 μg of platinum incorporated into each bilayer were obtained. Under acidic and/or reductive conditions, the amount and rate of platinum released from the capsules were increased, which are desirable traits for platinum-based anticancer drug delivery systems. Furthermore, in vitro evaluation showed that the PGA/PLL-Pt(IV) multilayer microcapsules displayed higher cytotoxicity (IC(50Pt) = 3.5 μg/mL) against colon cancer cells CT-26 than that of free cisplatin (IC(50Pt) = 8.6 μg/mL). This enhanced cytotoxicity was attributed to the effective internalization of the capsules by the cancer cells, which was observed by confocal laser scanning microscopy (CLSM) imaging.