Polymeric Microcapsules Research Articles

Oxygen delivery using engineered microparticles

A continuous supply of oxygen to tissues is vital to life and interruptions in its delivery are poorly tolerated. The treatment of low-blood oxygen tensions requires restoration of functional airways and lungs. Unfortunately, severe oxygen deprivation carries a high mortality rate and can make otherwise-survivable illnesses unsurvivable. Thus, an effective and rapid treatment for hypoxemia would be revolutionary. The i.v. injection of oxygen bubbles has recently emerged as a potential strategy to rapidly raise arterial oxygen tensions. In this report, we describe the fabrication of a polymer-based intravascular oxygen delivery agent. Polymer hollow microparticles (PHMs) are thin-walled, hollow polymer microcapsules with tunable nanoporous shells. We show that PHMs are easily charged with oxygen gas and that they release their oxygen payload only when exposed to desaturated blood. We demonstrate that oxygen release from PHMs is diffusion-controlled, that they deliver approximately five times more oxygen gas than human red blood cells (per gram), and that they are safe and effective when injected in vivo. Finally, we show that PHMs can be stored at room temperature under dry ambient conditions for at least 2 mo without any effect on particle size distribution or gas carrying capacity.

Microencapsulation of citronella oil for solar-activated controlled release as an insect repellent

This study investigates the functionalization of titanium dioxide nanoparticles on the surface of polymeric microcapsules as a mean to control the release of encapsulated citronella through solar radiation. This allows for the release of a mosquito repellent without human intervention, as the sunlight works as a release activator. The TiO2 nanoparticles were synthetized using a modified sol–gel and hydrothermal method, with a crystallite size of the order of 10nm and a specific surface area >250m2/g. Transmission electron microscopy observations enabled the confirmation of the mesoporous structure. The nitrogen doping effect and changes in pH (pH=3, 6 and 9) of the precursor solution was studied from photocatalytic and photoluminescence experiments. Polyurethane microcapsules were prepared using a modified interfacial polymerization method. The surface topography of the microcapsules was observed with scanning electron microscopy, while the release efficiency was quantified using gas chromatography coupled with mass spectroscopy. In-vitro bioassays using live mosquitoes further attested the controlled release repellence effect of these photocatalytic microcapsules by inhibition of these vectors. The results showed that functionalizing the microcapsules with nanoparticles on their surface and then exposing them to ultraviolet radiation effectively increased the output of citronella into the air, repelling the mosquitoes.

Microencapsulation of porcine thyroid cell organoids within a polymer microcapsule construct

Hypothyroidism is a common condition of hormone deficiency, and oral administration of thyroid hormones is currently the only available treatment option. However, there are some disadvantages with this treatment modality including compliance challenges to patients. Therefore, a physiologically based alternative therapy for hypothyroidism with little or no side-effects is needed. In this study, we have developed a method for microencapsulating porcine thyroid cells as a thyroid hormone replacement approach. The hybrid wall of the polymer microcapsules permits thyroid hormone release while preventing immunoglobulin antibodies from entry. This strategy could potentially enable implantation of the microcapsule organoids containing allogeneic or xenogeneic thyroid cells to secret hormones over time without the need for immunosuppression of recipients. Porcine thyroid cells were isolated and encapsulated in alginate-poly-L-ornithine-alginate microcapsules using a microfluidic device. The porcine thyroid cells formed three-dimensional follicular spheres in the microcapsules with decent cell viability and proliferation. Thyroxine release from the encapsulated cells was higher than from unencapsulated cells ( P < 0.05) and was maintained during the entire duration of experiment (>28 days). These results suggest that the microencapsulated thyroid cell organoids may have the potential to be used for therapy and/or drug screening.

Design of artificial red blood cells using polymeric hydrogel microcapsules: hydrogel stability improvement and polymer selection.

To improve the stability of pectin-oligochitosan hydrogel microcapsules under physiological conditions. Two different approaches were examined: change of the cross-linker length and treatment of the hydrogel microcapsules with 150 Mm CaCl2. Replacement of pectin with alginate was also studied. It was observed that the molecular weight of the cross-linker oligochiotsan had no significant improvement on microcapsule stability. On the other hand, the treatment of pectin-oligochitosan microcapsules with Ca2+ increased the microcapsule stability significantly. Different types of alginate were used; however, no red-blood-cell-shaped microcapsules could be produced, which is likely due to the charge-density difference between deprotonated pectin and alginate polymers.

Versatile synthesis of high performance, crosslinked polymer microcapsules with encapsulated n-hexadecane as heat storage materials by utilizing microsuspension controlled/living radical polymerization (ms CLRP) of ethylene glycol dimethacrylate with the SaPSeP method

When encapsulated n-hexadecane (HD) in polymer microcapsules is used for heat storage material, two problems that are the decreasing of latent heat (J/g-capsules, J/g-HD) and the generating of supercooling (ΔTs: °C) should be overcome. In previous studies, it was suggested that more polar polymer capsule shell and larger particle size were useful to improve the two problems, respectively. Based on the idea, first, 6-μm-sized, polar poly(ethylene glycol dimethacrylate) (PEGDM) particles with encapsulated HD were prepared by microsuspension conventional radical polymerization (ms CRP) with Self-assembly of Phase-Separated Polymer (SaPSeP) method that the authors proposed. As expected, the heat of solidification of the encapsulated HD (ΔHs* = 220 J/g-HD) was almost the same as that of pure HD (ΔHso = 230 J/g-HD) but the supercooling was still observed (ΔTs = 10 °C). Larger PEGDM particles (11- and 42-μm in diameter) prepared by the ms CRP “included” HD in the inside, but did not “encapsulate” it ideally, because they had porous structures. Ideal large PEGDM microcapsules (31 μm in diameter) with “encapsulated” HD were successfully prepared by utilizing microsuspension activators generated by electron transfer atom transfer radical polymerizations (ms AGET ATRP), which is one of controlled/living radical polymerization. They had excellent heat storage abilities (ΔHs = 105 J/g-capsules; ΔHs* = 210 J/g-HD; ΔTs = 6 °C).

UV-Triggered Self-Healing of a Single Robust SiO2 Microcapsule Based on Cationic Polymerization for Potential Application in Aerospace Coatings.

UV-triggered self-healing of single microcapsules has been a good candidate to enhance the life of polymer-based aerospace coatings because of its rapid healing process and healing chemistry based on an accurate stoichiometric ratio. However, free radical photoinitiators used in single microcapsules commonly suffer from possible deactivation due to the presence of oxygen in the space environment. Moreover, entrapment of polymeric microcapsules into coatings often involves elevated temperature or a strong solvent, probably leading to swelling or degradation of polymer shell, and ultimately the loss of active healing species into the host matrix. We herein describe the first single robust SiO2 microcapsule self-healing system based on UV-triggered cationic polymerization for potential application in aerospace coatings. On the basis of the similarity of solubility parameters of the active healing species and the SiO2 precursor, the epoxy resin and cationic photoinitiator are successfully encapsulated into a single SiO2 microcapsule via a combined interfacial/in situ polymerization. The single SiO2 microcapsule shows solvent resistance and thermal stability, especially a strong resistance for thermal cycling in a simulated space environment. In addition, the up to 89% curing efficiency of the epoxy resin in 30 min, and the obvious filling of scratches in the epoxy matrix demonstrate the excellent UV-induced healing performance of SiO2 microcapsules, attributed to a high load of healing species within the capsule (up to 87 wt %) and healing chemistry based on an accurate stoichiometric ratio of the photoinitiator and epoxy resin at 9/100. More importantly, healing chemistry based on a UV-triggered cationic polymerization mechanism is not sensitive to oxygen, extremely facilitating future embedment of this single SiO2 microcapsule in spacecraft coatings to achieve self-healing in a space environment with abundant UV radiation and oxygen.

The effect of varying volume fraction of microcapsules on fresh, mechanical and self-healing properties of mortars

Spherical polymeric microcapsules, carrying liquid sodium silicate, were used for autonomic self-healing of mortars. Microcapsules were added at varying volume fractions (Vf), with respect to the cement volume, from as low as 4% up to 32% and their effect on fresh, mechanical and self-healing properties was investigated. For this purpose a series of techniques were used ranging from static mechanical testing, ultrasonic measurements, capillary sorption tests and optical microscopy. A detailed investigation was also carried out at the microstructural level utilising scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX). Results showed that although increasing Vf resulted in a ∼27% reduction in the mechanical properties, the corresponding improvement in the self-healing potential was significantly higher. Areal crack mouth healing reached almost 100%. Also, the measured crack depth and sorptivity coefficient reduced to a maximum of 70% and 54% respectively in microcapsule-containing specimens. SEM/EDX observations showed that the regions in the periphery of fractured microcapsules are very dense. In this region, high healing product formation is also observed. Elemental analysis revealed that these products are mainly ettringite and calcium-silicate-hydrate (C-S-H).

Microcapsules for Confining Fluids: Prediction of Shell Stability from Advanced SAXS Investigations

Polymeric microcapsules represent an effective tool to confine a broad range of materials for diverse applications. Melamine-formaldehyde capsules have been extensively used to encapsulate fragrances (or other substances) in order to control the perfume release and to extend its efficacy. Capsule properties can be controlled and tuned by varying synthesis conditions, such as batch composition, pH and temperature. Their stability is certainly related to structural features such as mechanical, thermal and morphological characteristics. Nevertheless, to the best of our knowledge, a quantitative correlation between capsules leakage profiles and structural features has never been attempted. We report on a model based on the small angle X-ray scattering (SAXS) to describe the relationship between the homogeneous wall structure and the leakage properties of melamine capsules. SAXS is a suitable technique to investigate the structure of capsule shell at the nanometer scale and has been employed here to disclose t...

Catalytic Propulsion and Magnetic Steering of Soft, Patchy Microcapsules: Ability to Pick-Up and Drop-Off Microscale Cargo.

We describe the creation of polymeric microcapsules that can exhibit autonomous motion along defined trajectories. The capsules are made by cross-linking aqueous microdroplets of the biopolymer chitosan using glutaraldehyde. A coflow microfluidic tubing device is used to generate chitosan droplets containing nanoparticles (NPs) with an iron (Fe) core and a platinum (Pt) shell. The droplets are then incubated in a Petri dish with the cross-linking solution, and an external magnet is placed below the Petri dish to pull the NPs together as a collective "patch" on one end of each droplet. This results in cross-linked capsules (∼150 μm in diameter) with an anisotropic (patchy) structure. When these capsules are placed in a solution of H2O2, the Pt shell of the NPs catalyzes the decomposition of H2O2 into O2 gas, which is ejected from the patchy end in the form of bubbles. As a result, the capsules (which are termed micromotors) move in a direction opposite to the bubbles. Furthermore, the micromotors can be steered along specific paths by an external magnet (the magnetic response arises due to the Fe in the core of the NPs). A given micromotor can thus be directed to meet with and adhere to an inert capsule, i.e., a model cargo. Adhesion occurs due to the soft nature of the two structures. Once the cargo is picked up, the micromotor-cargo pair can be moved along a specific path to a destination, whereupon the cargo can be released from the micromotor. We believe these soft micromotors offer significant benefits over their existing hard counterparts because of their biocompatibility, biodegradability, and ability to encapsulate a variety of payloads.

Preparation and preliminary evaluation of alginate crosslinked microcapsules as potential drug delivery system (DDS) for human lung cancer therapy

Human lung cancer is the main cancer cause of death in men and the third cancer cause in women. As it is well-known, current antitumor treatments involve chemotherapy which mostly entails aggressive side effects. This study describes a drug delivery targeted strategy based in bioconjugated polymeric microcapsules with a size of around 30 μm. Alginate microcapsules, produced using a fan-jet nozzle, are used due to its biodegradability and biocompatibility and will be tested in vitro. Firstly, microparticles are prepared by ionic gelation of an alginate core sprayed on a barium chloride solution. Afterwards, epidermal growth factor is attached onto the surface of these microcapsules to specifically target non-small lung cancer cells (NSCLC). This bioconjugation is performed together with an anticancer agent, cisplatin. The in vitro studies of cytotoxicity has been tested with H460 lung cancer cell line and with controls on systems loaded with free drugs. In vitro validation tests were carried out in Petri plates and the cells viability were checked by MTT assay. These experiments showed that drug delivery treatment allows a faster mortality in H460 lung cancer cell plates. To sum up, this study reports the development of an advanced drug delivery system that improves the specificity issue on drug delivery in addition and in vitro confirmation in cell mediums containing NSCLC.

AFM Investigation of Liquid-Filled Polymer Microcapsules Elasticity.

Elasticity of polymer microcapsules (MCs) filled with a liquid fluorinated core is studied by atomic force microscopy (AFM). Accurately characterized spherical tips are employed to obtain the Young's moduli of MCs having four different shell thicknesses. We show that those moduli are effective ones because the samples are composites. The strong decrease of the effective MC elasticity (from 3.0 to 0.1 GPa) as the shell thickness decreases (from 200 to 10 nm) is analyzed using a novel numerical approach. This model describes the evolution of the elasticity of a coated half-space according to the contact radius, the thickness of the film, and the elastic moduli of bulk materials. This numerical model is consistent with the experimental data and allows simulating the elastic behavior of MCs at high frequencies (5 MHz). While the quasi-static elasticity of the MCs is found to be very dependent on the shell thickness, the high frequency (5 MHz) elastic behavior of the core leads to a stable behavior of the MCs (from 2.5 to 3 GPa according to the shell thickness). Finally, the effect of thermal annealing on the MCs elasticity is investigated. The Young's modulus is found to decrease because of the reduction of the shell thickness due to the loss of the polymer.

Preparation of polylactide microcapsules at a high throughput with a packed‐bed premix emulsification system

ABSTRACTCore–shell polymer microcapsules are well known for their biomedical applications as drug carriers when they are filled with drugs and gas‐filled microcapsules that can be used as ultrasound contrast agents. The properties of microcapsules are strongly dependent on their size (distribution); therefore, equipment that allows the preparation of small and well‐defined microcapsules is of great practical relevance. In this study, we made polylactide microcapsules with a packed‐bed premix emulsification system that previously gave good results for regular emulsions. Here, we tested it for applicability to a system in which droplets shrank and solidified to obtain capsules. The packed‐bed column was loaded with glass beads of different sizes (30–90 µm) at various bed heights (2–20 mm), and coarse emulsions consisting of the polymer, a solvent, and a nonsolvent were pushed repeatedly through this system at selected applied pressures (1–4 bar). The obtained transmembrane fluxes (100–1000 m3 m−2 h−1) were much higher than those recorded for other membrane emulsification techniques. The average size of the obtained microcapsules ranged between 2 and 8 µm, with an average span of about 1; interestingly, the capsules were 2–10 times smaller than the interstitial voids of the beds. The droplets were larger when we used thicker beds and larger glass beads, and these effect correlated with the pore Reynolds number (Rep). Two breakup mechanisms were identified: spontaneous droplet snap‐off dominated the system at low Reps, and localized shear forces dominated the system at higher Rep. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 43536.

Multicore expandable microbubbles: Controlling density and expansion temperature

Stable microbubbles can be prepared by evaporation of a liquid core inside an expandable polymeric shell. To control the expansion temperature and the size of resulting microbubbles, we prepared polymeric microcapsules that contain multiple liquids in their core. One-step suspension polymerization allowed for encapsulation of at least two different liquids with near quantitative yield. The liquids may be miscible or immiscible, which directly affects the vapor pressure inside the capsule according to either Raoult's or Dalton's law, respectively. In the case of miscible liquids, e.g., perfluorohexane and perfluoropentane, both the vapor pressure and the expansion temperature vary within a range bounded by the properties of the neat liquids. For immiscible liquids, e.g. perfluoropentane and isopentane, the total vapor pressure is above this range as it equals to a sum of the individual pressures. Due to increased vapor pressure, encapsulation of two immiscible liquids significantly lowers the expansion temperature below the corresponding temperatures observed during expansion of microcapsules with neat perfluoropentane and isopentane cores. The microbubble diameter and shell thickness were controlled within ca. 10–50 μm and 0.1–3 μm, respectively, by varying the fractions and vapor pressure of the core fluids. We also showed that the effect of core composition on the expansion temperature was more significant than the effect of the shell thickness. Furthermore, one of the encapsulated materials may carry additional functions including imaging contrast, catalysis, and density compensation. To that end, these designer microcapsules may find applications in the fields of drug delivery, acoustic imaging, drilling, and self-healing materials.

Innovative method of metal coating of microcapsules containing phase change materials

Microencapsulation of phase change materials (PCMs) is needed to prevent PCM leaking during melting. However, the low thermal conductivity of the microcapsules shell limits their applications. To enhance thermal conductivity of PCM microcapsules, a new method was developed for coating them with a metal using dopamine surface activation followed by electroless plating. The oxidative self-polymerization of dopamine (PDA) on the shell of the polymeric PCM microcapsules makes the surface active by providing chemisorption sites for metal deposition. Scanning electron microscope (SEM) images of the metal coated microcapsules without PDA pre-treatment did not show evidence of Ag metal on the surface of microcapsules. However, PCM microcapsules were completely covered with Ag metal when they were pre-treated with PDA as indicated by SEM and EDX tests. The enhancement in the thermal conductivity of silver coated PCM microcapsules of different size and for different silver coating coverage was investigated and discussed. This was confirmed by the enhancement in the performance of these silver-coated microcapsules using thermal cycling tests.

Encapsulation and Enhanced Retention of Fragrance in Polymer Microcapsules.

Fragrances are amphiphilic and highly volatile, all of which makes them a challenging cargo to efficiently encapsulate and retain in microcapsules using traditional approaches. We address these limitations by introducing a new strategy that combines bulk and microfluidic emulsification: a stable fragrance-in-water (F/W) emulsion that is primarily prepared from bulk emulsification is incorporated within a polymer microcapsule via microfluidic emulsification. On the basis of the in-depth study of physicochemical properties of the microcapsules on fragrance leakage, we demonstrate that enhanced retention of fragrance can be achieved by using a polar polymeric shell and forming a hydrogel network within the microcapsule. We further extend the utility of these microcapsules by demonstrating the enhanced retention of encapsulated fragrance in powder state.

In situ growth of fluorescent silicon nanocrystals in a monolithic microcapsule as a photostable, versatile platform.

A facile, one-step method was developed for the in situ formation of fluorescent silicon nanocrystals (SiNC) in a microspherical encapsulating matrix. The obtained SiNC encapsulated polymeric microcapsules (SiPM) possess uniform size (0.1-2.0 μm), strong fluorescence, and nanoporous structure. A unique two stage, time dependent reaction was developed, as the growth of SiNC was slower than the formation of polymeric microcapsules. The resulting SiPM with increasing reaction time exhibited two levels of stability, and correspondingly, the release of SiNC in aqueous media showed different behavior. With reaction time <1 h, the obtained low-density SiPM (LD-SiPM) as matrix microcapsules, would release encapsulated SiNC on demand. With >1 h reaction time, resulting high-density SiPM (HD-SiPM) became stable SiNC reservoirs. SiPM exhibit stable photoluminescence. The porous structure and fluorescence quenching effects make SiPM suitable for bioimaging, drug loading and sorption of heavy metals (Hg(2+) as shown) as an intrinsic indicator. SiPM were able to reduce metal ions, forming SiPM/metal oxide and SiPM/metal hybrids, and their applications in bio-sensing and catalysis were also demonstrated.

Inkjet printing based assembly of thermoresponsive core-shell polymer microcapsules for controlled drug release.

A controlled drug delivery system (DDS) was designed by integrating the thermoresponsive copolymer poly(N-isopropylacrylamide-co-methacrylic acid) (poly(NIPAAm-co-MAA)) with core-shell 1,6-hexanediol diacrylate (HDDA) microparticles. The monodisperse HDDA particles with a hollow core and a nanoporous shell were fabricated in a continuous manner by an initially proposed inkjet printing process combined with UV polymerization. The thermoresponsive poly(NIPAAm-co-MAA) copolymer was grafted onto the surface of HDDA microcapsules by free radical initiated polymerization. Particularly, the lower critical solution temperature (LCST) of the copolymer was adjusted to human physiological temperature by the optimal comonomer ratio of MAA. With temperature changes at around the LCST, the copolymer, which was modified on the internal nanopore, served as a "retractable gate" by virtue of its changes in conformation between swollen and collapsed structures. Thus, controlled drug release was achieved by the reversible "open-close" transition characteristics of the nanopores. Fluorescein as a hypothetical drug molecule was loaded in the microcapsules and used to investigate the controlled release of the material. The results confirmed that this system represents a promising candidate for use in preparing controlled DDSs.

Modeling of the controlled release of betacarotene into anhydrous ethanol from microcapsules

In this paper several models of the mass transfer process are described with the aim of simulating the release of active principles from matrix-type polymeric microcapsules. The following mathematical models, which are available in the literature, are applied in this study: Fick's second law (CDMASSA), the linear drive force (LDF), an analytical model and other semi-empirical models. The release of the active principle (betacarotene) contained in microcapsules (PHBV) into a solvent (ethanol) was investigated. It was observed that the model obtained with Fick's second law provided a better fit with the literature data compared with the LDF model, the analytical model and the semi-empirical models. It can be concluded from this finding that the most complete model, based on the phenomenology of the problem, provided the best result.

A copolymer capsule with a magnetic core for hydrophilic or hydrophobic drug delivery via thermo-responsive stimuli or carrier biodegradation

The glutathione-triggered and thermal-responsive polymer microcapsule carrier with magnetic core, Fe3O4@capsule is prepared for controlled release of hydrophilic or hydrophobic drug molecules.

Synthesis and characterization of a new polymeric microcapsule and feasibility investigation in self-healing cementitious materials

This paper presents work towards development of a new type of polymeric microcapsule with phenol–formaldehyde (PF) resin as shell and dicyclopentadiene (DCPD) as healing agent for self-healing microcracks in cementitious materials. The PF/DCPD microcapsules were synthesized via in-situ polymerization and characterized by means of optical microscope (OM), scanning electron microscope (SEM) and thermal analysis (TGA). The chemical stability of synthesized microcapsules and the trigger performance were studied respectively in simulated concrete pore solution and hardened cement paste specimens. The results revealed that the synthesized microcapsules possessed excellent stability in both simulated pore solution and real cement environment. X-ray computed tomography (XCT) was applied to observe the status and fracture behavior of microcapsules inside cement paste matrix. Further segmentation and 3D rendering of the reconstructed data obtained from XCT showed that the microcapsules had a good dispersibility with desired trigger sensitivity. The OM investigation of a fractured surface of a cement paste incorporated with microcapsules confirmed that the self-healing function of the microcapsules could be triggered by cracking and the healing agent could be released simultaneously to heal the cracks.