Fabrication of Hybrid Capsules via CaCO3 Crystallization on

Mar 19, 2018 - Fabrication of Hybrid Capsules via CaCO3 Crystallization on Degradable Coacervate Droplets ... Chemical Society. *Phone: +81-3-5876-141...
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Article Cite This: Langmuir 2018, 34, 3981−3986

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Fabrication of Hybrid Capsules via CaCO3 Crystallization on Degradable Coacervate Droplets Syuuhei Komatsu,† Yui Ikedo,† Taka-Aki Asoh,‡ Ryo Ishihara,† and Akihiko Kikuchi*,† †

Department of Materials Science and Technology, Tokyo University of Science, 6-3-1 Niijuku, Katsushika-ku, Tokyo 125-8585, Japan ‡ Department of Applied Chemistry, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-8585, Japan S Supporting Information *

ABSTRACT: Organic−inorganic CaCO3 capsules were prepared by crystallization of CaCO3 on Pickering emulsion prepared using coacervate droplets made from thermoresponsive and degradable poly(2-methylene1,3-dioxepane-co-2-hydroxyethyl acrylate) (poly(MDO-co-HEA)) in sole aqueous medium. The diameters of CaCO3-based Pickering emulsion could be controlled by varying several parameters: diameter of CaCO3 powders, initial polymer concentration, and copolymer composition. The CaCO3 Pickering emulsion was able to load low-molecular-weight hydrophobic substances at temperatures above the lower critical solution temperature (LCST) due to formation of polymer-concentrated phases, i.e., coacervate droplets. The diameter of CaCO3 capsules prepared by crystallization also depended on the diameter of the CaCO3 Pickering emulsion. The CaCO3 shell was composed of calcite-type crystals, the most stable polymorph among known CaCO3 crystals. The facially prepared CaCO3 capsules are valuable for use in functional biomaterials, such as drug delivery carriers and cell culture scaffolds for noninvasive bone-regenerative medicine.

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particles, like silica,18,19 CaCO3,12,20,21 ZnO,22 etc. Among these inorganic materials, CaCO3 has been focused on by many researchers because it is one of the constituents of bone and due to its excellent biocompatibility and drug release triggered by pH change.21,23,24 The emulsion can also be stabilized by further crystallization of CaCO3 on the surface of the Pickering emulsion. The formation of CaCO3 shells on the Pickering emulsion was reported for the water-in-oil phase.11 Utilization of organic solvents would limit the application of these emulsions in proteins and/or bioactive agents. Therefore, preparation of Pickering emulsion in sole aqueous medium is required for biomedical fields. Coacervation is a well-known phase separation technique applied for liquid−liquid phase separation to form coacervate droplets.25−29 The coacervate droplets are attractive for use as the core material of Pickering emulsions because these can envelop a variety of molecules like bioactive agents in sole aqueous medium.30,31 Thermoresponsive polymers would be one of the candidates to form coacervate droplets upon temperature change because these thermoresponsive polymers show either lower critical solution temperature (LCST)type32−34 or upper critical solution temperature (UCST)type35 phase separation. We previously prepared the thermoresponsive degradable polymer, poly(2-methylene-1,3-dioxepane

INTRODUCTION Core−shell particles have been used in a wide range of applications like impact modifiers, in sensing instruments, and in chromatography and drug delivery systems (DDS)1−6 because the core materials, either solid, liquid, or gas, of the core−shell particles are protected over long periods by the shell materials under different surrounding conditions. The properties of core−shell particles can be adjusted by designing the chemical structures of both core and shell and the size of the particles.7−9 Functional surface design using organic and/or inorganic materials is an important topic,5 because controlled surface property is a key factor for the application of core−shell particles in various fields, including biomedical fields. For example, polyelectrolyte,10 calcium carbonate (CaCO3),11,12 and hydroxyapatite (HAp)13 surfaces have been studied as shell materials for carriers in drug delivery systems and cell culture scaffolds in bone tissue engineering. Various kinds of core− shell particles have been synthesized by two- or multiple-step processes; for example, dry blending method,14 layer-by-layer (LbL) approach via electrostatic interaction,6 shell synthesis on preformed cores and spheres,15 etc. However, these methods are complex and a simpler preparation process may be needed. Formation of Pickering emulsions is an alternative method to prepare core−shell particles, in which the droplets are stabilized by small solid particles.11,12,16,17 Irreversible adsorption of small solid particles on the phase-to-phase interface is a well-known phenomenon. Thus, Pickering emulsions have been prepared from oil-in-water emulsions stabilized with inorganic solid © 2018 American Chemical Society

Received: January 17, 2018 Revised: March 18, 2018 Published: March 19, 2018 3981

DOI: 10.1021/acs.langmuir.8b00148 Langmuir 2018, 34, 3981−3986

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copolymer were analyzed by gel permeation chromatography (GPC) with Tosoh columns TSKgel G3000HHR and TSKgel G5000HHR connected serially, at 45 °C using dimethylformamide (DMF) containing 10 mmol L−1 LiCl as the eluent. Moreover, we prepared the fluorescent terpolymer, poly(MDO-co-HEA-co-Ac-Flu), using the same synthetic procedure. The characterization of poly(MDO-coHEA-co-Ac-Flu) is shown in Figure S2 and the properties listed in Table S1. The thermoresponsive behavior was determined by measuring the temperature-dependent transmittance changes of poly(MDO-co-HEA) using a UV−vis spectrophotometer (V-630Bio, JASCO, Tokyo, Japan) at 500 nm. The LCST was defined as the temperature at which 50% transmittance was recorded. Preparation and Characterization of CaCO3 Pickering Emulsion. CaCO3-based Pickering emulsions were prepared as follows: 2.0 wt % poly(MDO-co-HEA) aqueous solution containing 1.0 mol L−1 CaCl2 was mixed with dispersed CaCO3 (10 mg mL−1) while stirring at 30 °C for 2.5 h. The thermal condition used for preparing Pickering emulsions was defined as the temperature at which poly(MDO-co-HEA) showed liquid−liquid phase separation, forming coacervate droplets. Diameter measurement of the CaCO3-based Pickering emulsions was performed for droplets on glass coverslips using an inverted microscope (Keyence BZ-8100, Osaka) with a thermostated microwarm plate (Kitazato KM-01, Shizuoka, Japan) at 30 °C. The average diameter and size distribution of the formed Pickering emulsion were calculated from the microscopic images (three images; the sizes of the randomly selected 10 particles per image were measured to determine the average diameter). Rhodamine B (1 μg mL−1) was used as a relatively hydrophobic molecule during fluorescent microscopic observation (Keyence BZ-8100). Preparation of CaCO3 Capsules. Crystal growth of CaCO3 on Pickering emulsion was performed for 4 days at 30 °C in a closed glass vessel with a lid (8.0 cm × 8.0 cm × 8.0 cm, sealed with Teflon tape) together with ammonium carbonate (10 g/vessel) as a CO2 generator via thermal decomposition and concentrated H2SO4 (20 mL) as a trap agent for the liberated ammonia gas after preparation of the Pickering emulsion. The diameter and shell thickness of the CaCO3 capsules were calculated from the scanning electron microscopy images (SEM, JSM-6060, JEOL Ltd., Tokyo, Japan) (five images; the sizes of the randomly selected 2 particles per image were measured to determine the average diameter).

(MDO)-co-2-hydroxyethyl acrylate (HEA)) (poly(MDO-coHEA)), and found that this polymer showed LCST-type liquid−liquid phase separation in aqueous medium.32 The LCST of poly(MDO-co-HEA) has been controlled by varying the polymer composition and the polymer degraded to obtain hydrophilic oligomers upon pH change due to hydrolysis of the backbone ester groups derived from MDO. Herein, we focused on the formation of Pickering emulsions using coacervate droplets derived from poly(MDO-co-HEA) aqueous solution. In this study, we prepared organic/inorganic hybrid core−shell particles composed of CaCO3 capsules prepared by degradable coacervate droplets and crystallization of CaCO3 on the Pickering emulsion (Scheme 1). The Scheme 1. Illustration of the Pickering Emulsion Made with Coacervate Droplet and Crystallization of CaCO3

Pickering emulsion was simply prepared by mixing poly(MDO-co-HEA) and the CaCO3 particles at temperatures above the LCST. The diameters of the Pickering emulsion were regulated by polymer concentration, copolymer composition, and diameters of the CaCO3 particles. The CaCO3 particles on the Pickering emulsion were further stabilized by crystallization in CaCl2 aqueous medium. Moreover, degradability of the CaCO3 capsules was investigated at 37 °C under acidic conditions.

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RESULTS AND DISCUSSION Preparation and Analysis of CaCO3 Pickering Emulsion. In this study, the thermoresponsive degradable polymer, poly(MDO-co-HEA), having a LCST below 35 °C in water, was synthesized by radical copolymerization of MDO and HEA according to a previous report.32 The prepared poly(MDO-coHEA)s showed LCST-type liquid−liquid phase separation and formed coacervate droplets at 33 and 21 °C, respectively, in sole aqueous medium. The extent of phase separation decreased with increasing MDO content in the copolymer, as shown in Figure 1. Characterization of the copolymers is summarized in Table 1. In 0.5 mol L−1 CaCl2 aqueous solution, LCSTs of poly(MDOco-HEA) were decreased to 18 and 11 °C due to salting out effects. The result indicated that poly(MDO-co-HEA)s showed liquid−liquid phase separation in CaCl2 aqueous media. Next, the CaCO3-based Pickering emulsions were prepared by mixing 1.0 wt % poly(MDO-co-HEA) solution containing CaCl2 and dispersed CaCO3 with continuous stirring for a predetermined period at 30 °C (Scheme 1). Here CaCO3 particles with diameters of 1.3 and 7.2 μm were used. After mixing for 20 min, CaCO3 adsorbed on the coacervate droplet surfaces (Figure 2a). Self-assembly of CaCO3 on coacervate droplet surfaces occurred due to fluid−fluid interfacial effects and large interfacial energy of coacervate droplets due to instability of the emulsion.38 The coacervate droplets were completely

EXPERIMENTAL SECTION

Materials. 1,4-Butanediol, potassium t-butoxide (t-BuOK), tetrahydrofuran (THF), Dowex 50 (H+), 2,2′-azobis(4-methoxy-2,4dimethylvaleronitrile) (V-70), dimethyl sulfoxide (DMSO), rhodamine B, 2-hydroxyethylacrylate (HEA), ammonium carbonate ((NH4)2CO3), sulfuric acid (H2SO4), calcium chloride (CaCl2), and calcium carbonate (CaCO3) were purchased from Wako Pure Chemical Industries, Co., Ltd. (Osaka, Japan). A part of the CaCO3 was used as-purchased, and a part was ground in a mortar to reduce crystal size. Chloroacetaldehyde dimethylacetal and fluorescein oacrylate (Ac-Flu) were purchased from Sigma-Aldrich (MO, USA). DMSO was distilled under reduced pressure before use (0.5 kPa, 95.0 °C). 2-Methylene-1,3-dioxepane (MDO) was prepared by a two-step reaction according to previous reports.36,37 Synthesis of Thermoresponsive Degradable Poly(MDO-coHEA). Poly(MDO-co-HEA) was prepared by free radical ring-opening copolymerization of MDO and HEA using V-70 (2.0 mol % to the monomer) as a radical initiator in DMSO in nitrogen atmosphere at 30 °C for 24 h according to a previous report.32 The resultant solution was dialyzed against methanol for 3 days and against ultrapure water for 5 days using regenerated cellulose membrane tubing (Spectra/Por 3, MWCO: 3500); the water was changed every day before recovery of the products by lyophilization. The chemical structure of poly(MDOco-HEA) was determined by proton nuclear magnetic resonance (1H NMR) spectroscopy (1H NMR 600 MHz UltraShield, Bruker) (Figure S1). The number-averaged molecular weight and polydispersity of the 3982

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Figure 2. Microscopic image of preparation of Pickering emulsions made with coacervate droplets and CaCO3 using poly(MDO-co-HEA) (run 2) in 0.5 mol L−1 CaCl2 aqueous media. (a) Coacervate droplets without CaCO3. The scale bar is 100 μm. (b) Pickering emulsion. The scale bar is 100 μm. (c) Enlarged microscopic image of Pickering emulsion. The scale bar is 50 μm.

Figure 1. Temperature dependent transmittance of poly(MDO-coHEA). The green line and dotted line are run 1 in Table 1 in aqueous media with (dotted line) and without (line) 0.5 mol L−1 CaCl2. The black line and dotted line are run 2 in Table 1 in aqueous media with (dotted line) and without (line) 0.5 mol L−1 CaCl2.

Figure 3. Micrographic image of Pickering emulsion using poly(MDO-co-HEA-co-Ac- Flu) in 0.5 mol L−1 CaCl2 aqueous media. (a) Micrographic image of Pickering emulsion. (b, c) Fluorescent micrograph image of Pickering emulsion derived from poly(MDOco-HEA-co-Ac-Flu) (green fluorescence) and loaded rhodamine B (red fluorescence). All scale bars are 20 μm.

coated with CaCO3 after 150 min to form Pickering emulsion (Figure 2b). The size of the Pickering emulsion was relatively maintained. Figure 2c shows that CaCO3 particles were adsorbed on the coacervate surfaces. Therefore, coacervate droplets were stabilized with CaCO3 particles, without coalescence of the coacervate droplets. Moreover, we investigated the inside of the CaCO3 shell using the fluorescein-labeled thermoresponsive polymer, poly(MDO-coHEA-co-Ac-Flu). Figure 3 shows the microscopic images and fluorescent microscopic images of the Pickering emulsion obtained using fluorescein-labeled poly(MDO-co-HEA-coAcFlu) and rhodamine B as a hydrophobic marker low molecule. The poly(MDO-co-HEA-co-AcFlu) was concentrated in the Pickering emulsion (Figure 3b, green fluorescence), indicating that coacervate droplets existed in the core of the Pickering emulsion. Fluorescence of rhodamine B was also observed inside the Pickering emulsion (Figure 3c, red fluorescence). Both fluorescences arising from fluoresceinlabeled poly(MDO-co-HEA) and rhodamine B were observed in the same regions of the Pickering emulsion. As previously reported, coacervate droplets could entrap hydrophobic low molecules.32 These results indicated that the cores of the CaCO3 Pickering emulsions were prepared from concentrated and partly dehydrated polymer phase, i.e., coacervate droplets; thus, Pickering emulsions could be prepared on the basis of coacervate droplets under aqueous conditions without using oil phase. As poly(MDO-co-HEA) has ester groups in the main chain, stability of the Pickering emulsion would be decreased upon degradation of the polymer to become hydrophilic

oligomers. Successful formation of the Pickering emulsion thus indicated no degradation of the poly(MDO-co-HEA) during the preparation of the Pickering emulsion. It is well-known that diameters of solid particles covering the emulsion surface have a significant influence on the diameters of the Pickering emulsion.38 We then examined the effects of the size of CaCO3 crystals on the diameter of the obtained Pickering emulsions. Figure 4a shows the changes in the diameter of the CaCO3 Pickering emulsion prepared using different diameters of CaCO3 crystals. The average diameters of the used CaCO3 crystals are summarized in Table 2. The diameter of the coacervate droplets increased with time due to the unstable nature of the emulsion that led to coalescence of emulsion droplets (Figure 4a, triangle). However, the diameter of the coacervate droplets could not be determined after 20 min at 37 °C because the diameters were too large to observe under a microscope; eventually, liquid−liquid phase separations occurred with polymer-poor (above) and polymer-rich phases (bottom), as shown in Figure 4b (right). On the other hand, in the presence of CaCO3 particles, the diameters of the coacervate droplets remained within a certain diameter range, depending on the size of the CaCO3 particles. These results indicated that the coacervate droplets were stabilized with the adsorbed CaCO3 particles because the adsorbed CaCO3 layer worked as a physical barrier from coalescence on the coacervate

Table 1. Characterization of Poly(MDO-co-HEA)a copolymer feed

P(MDO-co-HEA)

run

MDO/HEA (molar ratio)

MDO (mmol)

HEA (mmol)

Mnb

Mw/Mnb

MDO ratioc (%)

yield (%)

LCST (°C)

1 2

2:8 3:7

0.4 0.6

1.6 1.4

130,000 110,000

3.0 2.5

7.3 12

80 75

34 21

a Polymerization of MDO with HEA was carried out in DMSO at 30 °C for 24 h. bNumber-average molecular weights (Mn) and polydispersity (Mw/ Mn) were measured by GPC using DMF containing 10 mmol L−1 LiCl as the eluent. The molecular weight standard was poly(ethylene glycol). c MDO contents were calculated from 1H NMR spectra measured in DMSO-d6.

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Figure 5. Polymer concentration dependent diameter change for the Pickering emulsion: open plot, 7.2 μm CaCO3; closed plot, 1.3 μm CaCO3.

Figure 4. (a) Time dependent diameter of coacervate droplets (closed triangle) and Pickering emulsion from different CaCO3 diameters (1.3 μm, open circles; 7.2 μm, closed circles). (b) Microscopic image of coacervate solution at 0 min (left) and 20 min (right) in closed pipettes at 37 °C in Figure 3a in 0.5 mol L−1 CaCl2 aqueous media.

poly(MDO-co-HEA)s with different MDO compositions (Figure S3). The result indicates that the diameter of Pickering emulsion prepared with polymers having high MDO content (15 mol %) was smaller than that obtained with low MDO content (7 mol %). This was probably due to the difference between the hydrophobicities of the coacervate droplet surfaces. The contact angle (θ) increased with increasing MDO content in the copolymers. Therefore, interfacial energy decreased for high MDO content, and the diameter of the Pickering emulsion decreased. These results indicated that the size of the Pickering emulsion could be controlled by varying the diameter of the solid particles, polymer concentration, and copolymer composition. Crystallization of CaCO3 Pickering Emulsion. We then investigated the stabilization of the CaCO3-based Pickering emulsions to transform them to CaCO3 capsules through crystallization of CaCO3 on the coacervate droplet surfaces. The Pickering emulsion underwent crystallization under CO2liberated conditions in the presence of Ca2+ ion (Figure 6). The spherical CaCO3 particles (diameter = 20.7 ± 5.4 μm) were a few microns larger than the as-prepared Pickering emulsion due to CaCO3 crystallization. The SEM image shows single spherical particles covered with CaCO 3 crystals. The crystallization of CaCO3 without coacervate droplets formed

Table 2. Average Diameter of Pickering Emulsion Using Different CaCO3 Crystals CaCO3 size (μm)

emulsion size (μm)

1.3 ± 0.3 7.2 ± 2.9

16.0 ± 4.1 61.9 ± 14.8

droplets. The diameter of the Pickering emulsion changed with the size of CaCO3, as summarized in Table 2 (CaCO3: 10 mg mL−1). The Pickering emulsion stabilized with 1.3 and 7.2 μm CaCO3 showed diameters of 16.0 ± 4.1 and 61.9 ± 14.8 μm, respectively. The smaller the diameter of the CaCO3 particles used, the smaller was the Pickering emulsion obtained, due to the interfacial energy (Eγ) for the stabilization of emulsion using solid particles,38 given by the following equation Eγ = πa 2γ(1 ± cos θ )2

(1)

where a is the diameter of solid particles, γ is the interfacial tension of polymer solution, and θ is the contact angle. According to eq 1, the diameter of the solid particles has a strong influence on the interfacial energy: it increases with increasing diameter of solid particles. Since interfacial tension of polymer solution and contact angle remain under the same conditions, the polymer concentration also remains unchanged. Therefore, the coacervate droplet coalescence due to the high interfacial energy before complete coverage with CaCO3 is obtained to yield stable Pickering emulsions. The obtained results were in good agreement with the report on Pickering emulsions stabilized by silica particles.39 Figure 5 shows that the diameter change of the Pickering emulsion depends on the polymer concentration. The diameter increased with increasing polymer concentration, with a larger change being observed above a polymer concentration of 0.25 wt % when 7.2-μm-sized CaCO3 particles were used. On the other hand, only a slight increase in the diameter of the Pickering emulsion was observed when 1.3-μm-sized CaCO3 was used. This was because the thermoresponsive phase separation and coacervation were dependent on the polymer concentration: the higher the polymer concentration, the easier the coalescence of the coacervate droplets. Therefore, the diameter of Pickering emulsions was tuned by changing the polymer concentration. We further investigated the effect of polymer composition on the diameter change for Pickering emulsion prepared using

Figure 6. Micrographic and SEM images of CaCO3 capsules using poly(MDO-co-HEA) and poly(MDO-co-HEA-co-AcFlu). (a) Micrographic image of CaCO3 capsules using poly(MDO-co-HEA-coAcFlu). The scale bar is 50 μm. (b) Fluorescent micrograph image of CaCO3 capsules derived from poly(MDO-co-HEA-co-AcFlu) (green fluorescence). The scale bar is 50 μm. (c, d) SEM images of CaCO3 capsules (the scale bar for part c is 20 μm, and that for part d is 10 μm). 3984

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culture scaffolds for bone medical treatment and regenerative medicine.

cubic calcite-type crystals (Figure S4). Figure 6b shows that the inner core of CaCO3 capsules showed green fluorescence, indicating the existence of the fluorescein-labeled poly(MDOco-HEA). Moreover, the coacervate droplets inside the CaCO3 capsules were characterized by using confocal laser scanning microscopy (Figure S5). The fluorescence of poly(MDO-coHEA-co-Ac-Flu) was observed and distributed uniformly inside the CaCO3 capsules. This result indicated that the poly(MDOco-HEA-co-Ac-Flu) was presented inside CaCO3 capsules to form a liquid core and CaCO3 existed as the shell. After crystallization, the red fluorescence derived from rhodamine B as the model hydrophobic substance was seen in the CaCO3 capsules (Figure S6). These capsules thus obtained have an encapsulation ability for hydrophobic substances similarly to the coacervate droplets. Therefore, the coacervate droplets remained within the particle core without degradation of poly(MDO-co-HEA) during crystallization, which supports the retention of drug molecules within the core of the Pickering emulsion. The XRD spectra obtained before and after crystallization of CaCO3 capsules (Figure S7) showed identical patterns for CaCO3 capsules and pristine CaCO3, which was in good agreement with the pattern for the calcite structure in the JCPDS database. The XRD spectra proved that the CaCO3 shell was prepared by a calcite-type CaCO3 crystal. CaCO3 is soluble under acidic conditions; thus, a dissolution test was performed for CaCO3 capsules in acidic solution at pH 1.2 as an accelerated test, and the result is shown in Figure S8. The CaCO3 capsules were dissolved completely after 24 h of incubation; a clear solution was then obtained after hydrolysis. Moreover, poly(MDO-co-HEA) inside the capsules also degraded under acidic conditions via hydrolysis of the ester groups on the polymer backbone, and the number-averaged molecular weight was changed from 67,000 to 27,000 after hydrolysis (Figure S8c). The CaCO3 capsules were thus found to be soluble and degradable under acidic conditions. These results suggest that the CaCO3 capsules will be used as base materials for the scaffold in hard tissues.

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ASSOCIATED CONTENT

S Supporting Information *

1

H NMR spectrum of poly(MDO-co-HEA). Characterization and 1H NMR spectrum of poly(MDO-co-HEA-co-Ac-Flu). The polymer concentration dependent diameter change for the Pickering emulsion. SEM image of CaCO3 without coacervate droplets after crystallization. Confocal laser fluorescence images of CaCO3 capsules. Microscopic images of CaCO3 capsules. XRD spectrum of CaCO3 capsules. Dissolution test of CaCO3 capsules in acidic condition. The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.langmuir.8b00148. Additional table and figures (PDF)

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AUTHOR INFORMATION

Corresponding Author

*Phone: +81-3-5876-1415. Fax: +81-3-5876-1639. E-mail: [email protected]. ORCID

Ryo Ishihara: 0000-0003-4862-4843 Akihiko Kikuchi: 0000-0002-7814-3656 Notes

The authors declare no competing financial interest.

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CONCLUSIONS In this study, CaCO3 capsules were successfully prepared using the Pickering emulsion made with degradable coacervate droplets in sole aqueous medium. The Pickering emulsions were prepared by adsorption of CaCO3 particles due to surfactant energy on coacervate droplets at temperatures above the LCST of poly(MDO-co-HEA). The diameter of the Pickering emulsions was controlled over a wide range (16− 62 μm) by varying the CaCO3 particle size, which led to the formation of a smaller Pickering emulsion with reduced CaCO3 particle size. Moreover, the diameter of the Pickering emulsion was controlled by varying the polymer concentration and composition of poly(MDO-co-HEA) due to the ease of coalescence of coacervate droplets. The CaCO3 capsules were prepared from the Pickering emulsion via crystallization of CaCO3. The shell of the Pickering emulsion was crystallized in CaCl2 aqueous solution, and the inner core was composed of poly(MDO-co-HEA). The shell of the capsules was calcite-type crystal, the most stable polymorph of CaCO3. Moreover, the CaCO3 capsules could be completely degraded in acid solutions. The CaCO3 shell was soluble, and the core was converted from thermoresponsive polymer to hydrophilic oligomer under acidic conditions. Accordingly, the CaCO3based Pickering emulsions prepared using poly(MDO-co-HEA) are expected to function as drug delivery carriers and cell 3985

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DOI: 10.1021/acs.langmuir.8b00148 Langmuir 2018, 34, 3981−3986