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DOI: 10.1039/C6RA19048K (Paper) RSC Adv., 2016, 6, 112292-112299

One-step fabrication of silica colloidosomes with in situ drug encapsulation

Yechao Su† a, Hong Zhao†a, Jinrong Wub and Jianhong Xu*a
aThe State Key Lab of Chemical Engineering, Department of Chemical Engineering, Tsinghua University, Beijing 100084, China. E-mail: xujianhong@tsinghua.edu.cn
bCollege of Polymer Science and Engineering, Sichuan University, Chengdu 610065, Sichuan, China

Received 27th July 2016 , Accepted 12th November 2016

First published on 18th November 2016

Abstract

Colloidosome is an important field of microencapsulation with various applications in catalysis, the food industry and pharmacy. Owing to its outstanding biocompatibility, silica colloidosomes are promising for biomedical applications. Nevertheless, silica modification as well as drug encapsulation are separated in some reported fabrication methods. In this article, bio-friendly materials SiO2 nanoparticles and chitosan are used in fabrication as dispersants. Pickering emulsion formed under the shear force of continuous phase n-octanol was further solidified and freeze-dried to obtain silica colloidosomes. In situ covalent modification of SiO2 nanoparticles' hydrophobicity by chitosan is the key to the formation of hollow silica colloidosomes and drug encapsulation can also be achieved during emulsion formation. By tuning the size of SiO2 nanoparticles and the solidification time of chitosan the size of interstices on the surface can be easily controlled to realize different release profiles of encapsulated drugs.

1 Introduction

Microencapsulation is a common method for material protection controlled release and is widely applied in the fields of catalysis,1–4 food industry5,6 and pharmacy.7–10 Various methods can be utilized to fabricate microcapsules, such as spray-drying,6 solvent phase separation11 and interfacial polymerization.12,13 Among the different morphologies of microcapsules, colloidosomes drew much attention for their advantages in precisely controllable permeability, compatibility and mechanical intensity by changing the type of colloids. Colloidosome is a novel class of microcapsules with coagulated or fused colloid particles at the interface of emulsion droplets.14 It is a kind of Pickering emulsion where colloids self-assemble on the surface of droplets to minimize the total interfacial energy. In 2002, Dinsmore et al.15 fabricated solid capsules by self-assembling colloidal PMMA particles onto the interface of emulsion droplets and named them as “colloidosomes”.

A large kinds of colloids can be utilized to fabricate colloidosomes, such as polymers like PS,16,17 metal oxide nanoparticles,1,18 and inorganic nonmetal nanoparticles.19,20 Recently, owing to its high biocompatibility, stability and chemical versatility, researches on carriers made from silica nanoparticles in drug delivery have rapidly increased. For example, silica colloidosomes have high potential in application in drug/gene delivery21 and smart coating formulations.22 Nowadays, the main methods of fabricating silica colloidosomes can be categorized as follows. One is polymerization at the interface of Pickering emulsion.23 Chen et al.24 used 2-bromoisobutyrate-functionalized silica nanoparticles for stabilization of oil–water Pickering emulsion, then poly(2-hydroxyethyl methacrylate) (PHEMA) was grafted and slightly cross-linked to prepare colloidosomes. Another widely utilized method is layer-by-layer assembly.25,26 Rossier-Miranda et al.27 prepared microcapsules through electrostatic LbL assembly using protein/pectin shell and charged colloidal silica, and the microcapsules can be loaded and closed at will by adding high methoxyl pectin/whey protein. However, there are three main drawbacks of these methods, one is that colloidal silica particles are usually chemically pre-modified to form Pickering emulsion, which would increase the complexity of producing process and influence its biocompatibility. Another is that the encapsulation process is separated with fabrication of colloidosomes, especially in layer-by-layer assembly method, while post-encapsulation often leads to the decrease in loading capacity of inner cargoes and increase the cost of encapsulation. Furthermore, the size uniformity of colloidosomes is hard to control. To overcome those disadvantages, microfluidic preparation of silica colloidosomes was achieved by Lee et al.28 In their experiment, hydrophobic silica nanoparticles dispersed in oil formed water-in-oil-in-water (W/O/W) double emulsion and eventually became colloidosome after oil removal. The colloidosomes fabricated possess high size uniformity and their dimensions can be precisely controlled. Still, the process as well as the micro device is complex, and chemicals like toluene and chloroform were used in fabrication, which might influence the performance of drugs encapsulated inside. Consequently, a simple microfluidic method for preparing silica colloidosome microcapsules is in grave need.

Herein, we propose a way of one-step preparing uniform nanostructured SiO2 colloidosome microcapsules in a co-axial microfluidic device, where the microcapsules were fabricated by the self-assembly of SiO2 nanoparticles in situ chemically modified with biocompatible chitosan and further covalent cross-linking on the surface of droplets. The interaction between SiO2 nanoparticles and chitosan along with cross-linking of chitosan under the effect of glutaraldehyde is the key to formation of stable Pickering emulsion. The encapsulation process is also in situ by adding the components into the dispersed phase before droplet formation in microchannel and microcapsules with hollow cavity can be easily acquired by washing and freeze-drying afterwards. The method is facile and conquered the problems of loss in biocompatibility, loading capacity, low size uniformity and complex process in reported methods. Colloidosome prepared in this way is a promising drug carrier for sustained drug release.

2 Materials and methods

2.1 Materials and chemicals

Chitosan with a deacetylation degree below 95% (purchased from Sinopharm Chemical Reagent Co., Ltd., Beijing, PR China) was dissolved in 2 wt% acetic acid solution for further use. Nano-structured SiO2 particles were prepared as reported in our previous work,29 and particles with different kinds of size were obtained by modifying the amount of ammonia and H2O used in the Stöber synthesis composition. Upon usage, nano-structured SiO2 particles were obtained after centrifugation of their ethanol solution and washed with deionized water, then solution with different weight percentage of nano-structured SiO2 particles were prepared. FITC–dextran with different molecular weight (70 kDa and 150 kDa) were purchased from Sigma Aldrich. n-Octanol (purchased from VAS Chemical Co., Ltd., Tianjin, PR China) was used as the continuous phase. Glutaraldehyde (0.040 g, purchased from VAS Chemical Co., Ltd., Tianjin, PR China) dissolved in n-octane (10.0 g, purchased from VAS Chemical Co., Ltd., Tianjin, PR China) were used as the solidification bath with glutaraldehyde as the cross-linking reagent.

2.2 Microfluidic device

The microfluidic device was fabricated on two 30 mm × 20 mm × 4 mm PMMA plates using micromachining technology. The diameter of perpendicularly crossing channels was 1 mm, and Teflon tube with a 0.9 mm inner diameter was inserted as the continuous phase inlet and dispersing phase inlet to form the co-axial structure. The microfluidic device was obtained by further sealing the two PMMA plates together. Three microsyringe pumps and three gastight microsyringes were used to pump the fluids into the microfluidic device. The droplets forming in the Teflon tube were collected in the solidification bath.

2.3 Preparation of monodispersed nano-structured SiO2 microcapsules

In terms of dispersed phase, typically 50 μL water solution of nano-structured SiO2 was mixed with 50 μL 2 wt% chitosan solution, following an addition of 900 μL deionized water. The concentration of chitosan in dispersant can be easily controlled by varying the addition of chitosan solution. When used for CLSM observation, 850 μL deionized water was added instead and 50 μL FITC–dextran solution with mass concentration of 0.2 mg mL−1 was replenished. It took several hours before further preparation to make sure the nano-structured SiO2 particles interact with chitosan thoroughly. To prepare nano-structured SiO2 microcapsules, the dispersed phase fluid was injected into the co-axial microchannel at the rate of 15 μL min−1, while the continuous phase was injected at the rate from 200 μL min−1 to 800 μL min−1. Dispersed fluid was separated into mono-dispersed droplets by the shear force of the continuous phase and flowed into the solidification bath. The Schiff base reaction between glutaraldehyde and chitosan and the extraction of water by n-octanol were employed to pre-solidify the droplets in the solidification bath. Different solidification time was applied to study the effect on microcapsule structure.

After solidification, the microspheres were washed with n-octane and then freeze-dried for further observation.

2.4 Analysis and characterization

The droplets and microspheres were first observed using an optical microscope (Type BX-61, Olympus, Japan) and an on-line CCD (PixeLINK, Canada). Scanning electron microscopy (SEM, type TM3000 and type JS6301F, Hitachi, Japan) was used to observe the detailed structures of the microspheres. The microcapsules in solidification bath were first washed using deionized water then was transferred into Petri dish with deionized water. Fourier spectrophotometer (Tensor 27, Bruker Optics, Germany) was used to determine the interaction between chitosan and SiO2 nanoparticles. Co-focal laser scanning microscopy (Type BX-61, Olympus, Japan) was used to observe the release behavior of FITC–dextran in microcapsules.

3 Results

3.1 Formation and characterization of the nano-structured SiO2 colloidosomes

As the dispersed phase was injected into the microchannel, droplets are formed by the shearing force of continuous phase in the Teflon tube, as shown in Fig. 1a. In the solidification bath, glutaraldehyde diffused into droplets and reacted with chitosan via the Schiff base reaction as water was, on the contrary, extracted out of the droplets by n-octanol in the solidification bath to ensure pre-solidification of the microspheres. Different degree of solidification can be achieved by merely tuning the time of solidification.
image file: c6ra19048k-f1.tif
Fig. 1 (a) Diagram of the experiment device. (b) Micrograph of the SiO2 nanoparticles/chitosan droplets. (c) SEM image of SiO2 colloidosomes. (d) SEM image of sectioned SiO2 colloidosomes.

Typical nano-structured SiO2 microcapsules formed with 0.0636 wt% SiO2 nanoparticles and 0.1 wt% chitosan in the dispersed phase, solidified for 4 h were used as samples to characterize the component distributions on the surface of microcapsule and its hollow structures. Fig. 1b shows that the droplets possess uniform size distribution as well as good sphericity, with the coefficient of variance (CV) 0.017. After washing and further freeze drying, the microspheres were observed under scanning electron microscope (SEM), from Fig. 1c it can be seen that the microspheres are slightly distorted during post-treatment and have a sphere-like morphology, with a little crumpled surface. To verify the hollow microcapsule structure, microspheres were cut open and a typical section is shown in Fig. 1d. It was found that the microspheres had a thin shell and a hollow inner compartment, thus the structure of microcapsules is verified.

3.2 Effect of the concentration of SiO2 nanoparticles and chitosan on the structure of colloidosomes

To investigate the effect of the concentration of SiO2 nanoparticles and chitosan on the structure of colloidosomes, microspheres with different concentration of SiO2 nanoparticles and chitosan were prepared and observed, as shown in Fig. 2. When the concentration of chitosan was higher than 0.2 wt%, the microspheres formed were solid whatever the concentration of SiO2 nanoparticles is, while the latter is mainly distributed on the surface of microspheres. However, with the decrease of chitosan concentration, the structure assembled by SiO2 nanoparticles became increasingly uniform and consistent. When the concentration of chitosan reached 0.2 wt% and less, microspheres with hollow structure were obtained, with a thin chitosan shell and assembled nanoparticles on it. Further decrease of the concentration of SiO2 nanoparticles and chitosan can realize the formation of microcapsules with reduced thin-layer SiO2 nanoparticles, though their mechanic intensity might be low and fragile, as shown in Fig. 2f. Therefore, we fabricated colloidosomes with multilayers of packed SiO2 nanoparticles on the shell to achieve a balance between mechanical intensity and release behavior, as shown in Fig. 2i.
image file: c6ra19048k-f2.tif
Fig. 2 SEM images of chitosan/SiO2 nanoparticles hybrid microspheres with different concentration of chitosan. The first row shows the overall morphology of microspheres, and the second row shows the surface morphology of microspheres. (a and f), (b and g), (c and h), (d and i) are the microspheres fabricated with 1.8 wt%, 1.4 wt%, 0.4 wt% and 0.1 wt% chitosan respectively. (e) and (j) shows colloidosome with different layers of SiO2 nanoparticles.

3.3 Mechanism of the formation of colloidosome

3.3.1 Scheme for the in situ chemical modification of SiO2 nanoparticles and the formation of colloidosome. Previous study30 has proposed a theory that strong Si–O covalent bonds are formed between the silanes and the chitosan rather than weak Si–N bond, and another research31 revealed that although the amine groups of chitosan don't participate in the formation of covalent bonds, their protonated NH3+ form in acid solution serves as hydrogen bonding partner and strengthens the interaction between silane and chitosan as a result. Similarly, in our experiment, the silanol groups existing on the surface of SiO2 nanoparticles interact with the hydroxyl groups of chitosan, forming strong Si–O covalent bonds, and the oxygen atoms can also interact with the amine groups of chitosan through hydrogen bonding as silane do. Fig. 3a shows the interaction.
image file: c6ra19048k-f3.tif
Fig. 3 Scheme of the formation of colloidosomes: (a) interaction between SiO2 nanoparticles and chitosan through covalent bonding and hydrogen bonding. (b1) Droplet collected in the solidification bath. (b2) SiO2 nanoparticles interact with chitosan, forming amphiphilic structures and self-assembly on the interface of droplet, while glutaraldehyde diffuses into the droplet and start crosslinking with chitosan, and the water is extracted outward, leading to the shrinkage of droplet. (b3) Chitosan is crosslinked into a thin shell after certain time, bonding SiO2 nanoparticles. A hollow core–shell structure is formed.

SiO2 nanoparticle is basically hydrophilic substance due to the large amount of silanol groups on its surface. Still, as the interaction between SiO2 nanoparticles and chitosan proceeds, the long chain of chitosan exhibiting slight hydrophobicity turns the SiO2 nanoparticles into amphiphilic substance. As a result, instead of staying in the droplets, SiO2 nanoparticles are inclined to move towards the interface between droplets and oil phase, as most surfactants behave. Therefore, SiO2 nanoparticles bonded with chitosan molecules self-assemble on the surface of the droplet as the cross-link reaction continues between chitosan and glutaraldehyde that diffused into the droplet. If the reaction is complete and chitosan is cross-linked thoroughly, a thin chitosan shell would occur on the surface of droplet with SiO2 nanoparticles bonded to it. The cross-linkage between chitosan bonded to different SiO2 nanoparticles keeps the package of SiO2 nanoparticles stable and forms ordered array near the chitosan shell, as shown in Fig. 3b.

3.3.2 Verification of the proposed scheme. Traditionally, as the concentration of chitosan decreases, pure chitosan microspheres formed by reaction with glutaraldehyde and extraction of water in the droplets would be solid or porous, based on the solidification time of droplets in the solidification bath. Nevertheless, from the experimental result, hollow microcapsules were prepared. In order to test our scheme, several parallel experiments were conducted. One is to prepare the pure chitosan microspheres under the same concentration of chitosan, solidification time and flow rate of continuous phase, without the addition of SiO2 nanoparticles. It can be seen from Fig. 4a that the microsphere is porous from outside to inside, unlike the hollow structure obtained in our former experiment. Another experiment was conducted in our previous study, where the SiO2 nanoparticle itself and its concentration is the same as what is used in our work. It can also be clearly seen from Fig. 4b that the microspheres fabricated possess a solid structure, still differ from the microcapsule obtained in our work. Therefore, the interaction between SiO2 nanoparticles and chitosan is requisite in the formation of microcapsule structure. Moreover, the cross-linkage of chitosan is also significant since the linkage holds the packed SiO2 nanoparticles together and grants the microcapsule with stability in the solution. In a corresponding experiment, glutaraldehyde wasn't added into the solidification bath, after the same solidification time, the droplets were transferred into the deionized water, while they were dissolved at the instant. On the contrary, solidified microcapsules were stable in the water as expected, indicating the importance of solidification in formation of stable SiO2 colloidosomes. Subsequent energy spectrum analysis result in Fig. 4c further confirms the existence of chitosan as well as SiO2 on the surface of fabricated colloidosomes.
image file: c6ra19048k-f4.tif
Fig. 4 (a) SEM image of microsphere fabricated under the same condition as Fig. 1c except without the addition of SiO2 nanoparticles. (b) SEM image of microsphere fabricated under the same condition as Fig. 1c except without the addition of chitosan. (c) Results of the energy spectrum of SiO2 colloidosomes on the surface.

To further determine the interaction between SiO2 nanoparticles and chitosan, the Fourier transform infrared (FT-IR) spectra of solid samples of dispersant was collected with a Fourier spectrophotometer (Tensor 27, Bruker Optics, Germany). The results are listed in Fig. 5.


image file: c6ra19048k-f5.tif
Fig. 5 FT-IR spectrum of (a) SiO2 nanoparticles and (b) silica colloidosomes.

Sample of silica nanoparticles, modified with hydroxyl groups on the surface, as Fig. 5a shows, have two intense peaks around wave number 800 and 1000. The former peak indicates the existence of Si–OH bonds, and the latter peak indicates the existence of Si–O–Si bonds.

Sample of silica colloidosomes, fabricated by dispersed phase with SiO2 nanoparticles modified by chitosan, as Fig. 5b shows, have only one intense peak around wave number 1000 while the peak at wave number 800 is much weaker than that in the silica nanoparticles, which suggest that Si–OH bonds are replaced in other covalent interaction, unfortunately, the Si–O–C bond peaks at wave number 1000 to 1200 as well, so we can't directly confirm its formation. However, judging from the result and former studies, the probability of formation of Si–O bonds between silica nanoparticles and chitosan is high.

To conclude, based on the result of parallel experiments and FT-IR characterization, our proposed scheme clarifies the formation process of nano-structured SiO2 microcapsules, that is, the in situ chemical modification on SiO2 nanoparticle with chitosan to change its hydrophilicity, making it concentrates on the interface between droplets and oil phase, and the further cross-linking reaction facilitates the formation of stable SiO2 nanoparticle array on the chitosan shell of microcapsules. Hollow microcapsules are obtained afterward.

3.4 Study of the release pattern of nanostructured SiO2 microcapsule

The ability of nanostructured SiO2 microcapsules as nano-carriers to release inner cargoes has been explored. FITC modified dextran (a hydrophilic fluorescent dye) was chosen as the model drug for encapsulation into the microcapsules. Typically, droplets with FITC–dextran formed under the flow rate 800 μL min−1 of continuous phase were collected into solidification bath and solidified for 8 h, following with washing before being transferred into deionized water to initiate release. Experiments under different conditions were conducted and Co-focal Laser Scanning Microscopy (CLSM) was utilized to investigate the release pattern of nanostructured SiO2 microcapsules. Without further explanation, the microcapsules in these experiments were prepared under the condition that the flowrate of continuous phase is 800 μL min−1 and the solidification time is 8 h.

The capsules still possess high sphericity and their shells weren't compromised after encapsulation, with FITC–dextran filled evenly inside the cavity of microcapsules, as shown by Fig. 6a. The dissipation of the fluorescence over time were observed under different experimental conditions. It can be seen from Fig. 6c that the fluorescence intensity kept decreasing in each experiment and reached a constant low level after 24 h. That was because of the fluorescence of chitosan in microcapsule, which has been verified by Wei32 and Zhao.33 While the plot in Fig. 6b shows the trend of decreasing of fluorescence intensity analyzed by the software Image Pro Plus 7.0 with initial fluorescence intensity in each experiment set at 100%. According to An's work,34 we modified and assumed that the release of FITC–dextran can be fitted as exponential decay model, with the function:

 
I = I0e−At (1)
I refers to the fluorescence intensity after t hour while I0 refers to the initial fluorescence intensity. The coefficient A is related to the permeability and the radius of the capsule. The result of fitting is listed in Table 1.


image file: c6ra19048k-f6.tif
Fig. 6 (a) Fluorescence image of unsolidified droplets formed under the flow rate 200 μL min−1 of continuous phase. (b) Plot of the changes in fluorescence intensity over time of colloidosomes prepared and encapsulated under different experimental conditions. (c–e) Fluorescence images of the process of FITC–dextran release in water of colloidosomes prepared and encapsulated under different condition. (c) Colloidosome with small interstices and encapsulated with 70 kDa FITC–dextran. (d) Colloidosome with small interstices and encapsulated with 150 kDa FITC–dextran. (e) Colloidosome with large interstices and encapsulated with 70 kDa FITC–dextran. (f) Fluorescence images of the process of FITC–dextran release in oil phase n-octane of colloidosome in (c). All scale bars are 100 μm.
Table 1 Half-life of dextran release of different prepared colloidosomes
Colloidosome A Half-life/h R2
Small interstices – 70 kDa 0.067 10.3 0.9823
Small interstices – 150 kDa 0.081 8.6 0.9205
Large interstices – 70 kDa 0.18 3.9 0.9628

3.4.1 Effects of the molecular weight of FITC–dextran on the release pattern of nanostructured SiO2 microcapsule. As the molecular weight of FITC–dextran increased from 70 kDa (Fig. 6c) to 150 kDa (Fig. 6d), the dissipation of the fluorescence became slower over time, which can also be noticed on the plot in Fig. 6b, where the red line represents the decrease in fluorescence intensity of 150 kDa FITC–dextran experiment while the black line corresponds to the 70 kDa FITC–dextran experiment.

This is because that the microcapsules prepared in both experiments were under the same condition, thus they share the same nanostructure on the shell and the interstices formed between packed SiO2 nanoparticles and cross-linkage of chitosan have the same size. Nevertheless, the permeability of microcapsule to FITC–dextran varies as its molecular size changes due to molecular weight difference. Therefore, for larger FITC–dextran molecules with higher molecular weight, the diffusion outward through the shell became harder and the intensity of fluorescence decreased slower as a result.

3.4.2 Effects of the size of interstices on the release pattern of nanostructured SiO2 microcapsule. Fig. 6e represents the fluorescence change over time of the microcapsule fabricated with larger SiO2 nanoparticles (particle size: 220 nm), shorter solidification time (2 h) and encapsulated with 70 kDa FITC–dextran (Fig. 7a), meanwhile the blue line in Fig. 6b shows its trend of changes in fluorescence intensity. In comparison, Fig. 7b shows the SEM photo of the surface structure of microcapsule in Fig. 6c. Combined with the blue line and the black line in Fig. 6b, conclusion can be made that for those with larger SiO2 nanoparticles and lesser solidification time, the dissipation of the fluorescence was much faster in the same period of time. It has been stated that the interstices on the peripheral shell layer were formed by the package of SiO2 nanoparticles and the cross-linkage of chitosan. Although colloidosome in Fig. 7b was fabricated with smaller SiO2 nanoparticles, but the solidification of chitosan was more complete, increasing the size of nanoparticles and the compactness of package. So the variance in the size of SiO2 nanoparticles and the solidification time both influenced the size of interstices, hence led to the difference in diffusion rate of FITC–dextran and the distinction in the trend of fluorescence change over time.
image file: c6ra19048k-f7.tif
Fig. 7 SEM image on surface structure of different nanostructured SiO2 colloidosomes. (a) Colloidosome prepared with larger SiO2 nanoparticles (particle size: 220 nm) and shorter solidification time (2 h). (b) Colloidosome prepared with smaller SiO2 nanoparticles (particle size: 160 nm) and longer solidification time (8 h).
3.4.3 Determination of the release behavior in water. Since the fluorescence of FITC–dextran would decrease as time passes under the effect of quenching, confirmation should be made that the decrease in fluorescence in former experiments were attributed to the release of fluorescence molecules rather than their quenches. Parallel experiment was conducted in which microcapsules prepared under the same condition were transferred into n-octane rather than water, and Fig. 6f shows the change of fluorescence intensity in oil compared with change in water. As FITC–dextran is hydrophilic, it wouldn't diffuse outward when the microcapsules were immersed in n-octane, therefore, their fluorescence intensity kept nearly unchanged even after 22 h.

To sum up, the release behavior of FITC–dextran in microcapsules was confirmed and studied, and the molecular weight of inner cargoes and the size of SiO2 nanoparticles both had significant effect on the release behavior of microcapsules. Microcapsules fabricated with larger SiO2 nanoparticles had better permeability for smaller cargoes encapsulated inside. With specific control on these traits of microcapsules, microcapsules that have different half-life of sustained drug release patterns can be prepared.

4 Conclusions

Silica colloidosomes with high size uniformity and sphericity were one-step fabricated through the self-assembly of SiO2 nanoparticles in a co-axial microfluidic channel. After modification of the composition of components in dispersed phase, silica colloidosomes with hollow core–shell structure were obtained using SiO2 nanoparticles in situ chemically modified with chitosan to form stable Pickering emulsion. Further covalent-crosslinking of chitosan granted the stability of silica colloidosomes. In situ encapsulation of cargoes can also be easily achieved through adding components directly into dispersant before droplet formation. Different release profiles of colloidosomes could be controlled by tuning the size of SiO2 nanoparticles and the solidification time of chitosan. It is more difficult for FITC–dextran as model drugs to diffuse outwards when loaded in silica colloidosomes formed by smaller nanoparticles. Moreover, FITC–dextran with larger molecular weight is also more difficult to diffuse outwards due to its larger molecular size. The in situ modification strategy can be applied to the preparation of other colloidosomes if covalent or other interaction occurs between colloidal particles and modifier that can enhance the amphiphilicity of colloidal particles and promote the formation of Pickering emulsion. The fabrication method is facile, controllable and promising in preparing silica colloidosomes as drug carriers for sustained drug release.

Acknowledgements

The authors gratefully acknowledge the supports of the National Natural Science Foundation of China (21322604, 21476121).

References

  1. B. Samanta, X.-C. Yang, Y. Ofir, M.-H. Park, D. Patra, S. Agasti, O. Miranda, Z.-H. Mo and V. Rotello, Angew. Chem., Int. Ed., 2009, 48, 5341–5344 CrossRef CAS PubMed.
  2. E. W. Stein, D. V. Volodkin, M. J. McShane and G. B. Sukhorukov, Biomacromolecules, 2006, 7, 710–719 CrossRef CAS PubMed.
  3. C. Zhang, C. Hu, Y. Zhao, M. MÃűller, K. Yan and X. Zhu, Langmuir, 2013, 29, 15457–15462 CrossRef CAS PubMed.
  4. T. Okada, K. Miyamoto, T. Sakai and S. Mishima, ACS Catal., 2014, 4, 73–78 CrossRef CAS.
  5. V. Chandramouli, K. Kailasapathy, P. Peiris and M. Jones, J. Microbiol. Methods, 2004, 56, 27–35 CrossRef CAS PubMed.
  6. G. Gallardo, L. Guida, V. Martinez, M. C. LÃşpez, D. Bernhardt, R. Blasco, R. Pedroza-Islas and L. G. Hermida, Food Res. Int., 2013, 52, 473–482 CrossRef CAS.
  7. L.-Y. Chu, T. Yamaguchi and S. Nakao, Adv. Mater., 2002, 14, 386–389 CrossRef CAS.
  8. Y. Chen, Q. Meng, M. Wu, S. Wang, P. Xu, H. Chen, Y. Li, L. Zhang, L. Wang and J. Shi, J. Am. Chem. Soc., 2014, 136, 16326–16334 CrossRef CAS PubMed.
  9. I. I. Slowing, J. L. Vivero-Escoto, C.-W. Wu and V. S. Y. Lin, Adv. Drug Delivery Rev., 2008, 60, 1278–1288 CrossRef CAS PubMed.
  10. L. Liu, J.-P. Yang, X.-J. Ju, R. Xie, Y.-M. Liu, W. Wang, J.-J. Zhang, C. H. Niu and L.-Y. Chu, Soft Matter, 2011, 7, 4821–4827 RSC.
  11. O. J. Cayre and S. Biggs, J. Mater. Chem., 2009, 19, 2724–2728 RSC.
  12. J. Zhang, R. J. Coulston, S. T. Jones, J. Geng, O. A. Scherman and C. Abell, Science, 2012, 335, 690–694 CrossRef CAS PubMed.
  13. Y. Zheng, Z. Yu, R. M. Parker, Y. Wu, C. Abell and O. A. Scherman, Nat. Commun., 2014, 5, 5772 CrossRef CAS PubMed.
  14. P. F. Noble, O. J. Cayre, R. G. Alargova, O. D. Velev and V. N. Paunov, J. Am. Chem. Soc., 2004, 126, 8092–8093 CrossRef CAS PubMed.
  15. A. D. Dinsmore, M. F. Hsu, M. G. Nikolaides, M. Marquez, A. R. Bausch and D. A. Weitz, Science, 2002, 298, 1006–1009 CrossRef CAS PubMed.
  16. K. Xu, J.-H. Xu, Y.-C. Lu and G.-S. Luo, Cryst. Growth Des., 2013, 13, 926–935 CAS.
  17. G. Stephenson, R. M. Parker, Y. Lan, Z. Yu, O. A. Scherman and C. Abell, Chem. Commun., 2014, 50, 7048–7051 RSC.
  18. J. S. Sander and A. R. Studart, Langmuir, 2011, 27, 3301–3307 CrossRef CAS PubMed.
  19. Y. Zhao, N. Dan, Y. Pan, N. Nitin and R. V. Tikekar, J. Food Eng., 2013, 118, 421–425 CrossRef CAS.
  20. F. Nan, J. Wu, F. Qi, Q. Fan, G. Ma and T. Ngai, J. Mater. Chem. B, 2014, 2, 7403–7409 RSC.
  21. K. Zhang, W. Wu, K. Guo, J. Chen and P. Zhang, Langmuir, 2010, 26, 7971–7980 CrossRef CAS PubMed.
  22. H. Wang, X. Zhu, L. Tsarkova, A. Pich and M. MÃűller, ACS Nano, 2011, 5, 3937–3942 CrossRef CAS PubMed.
  23. L. A. Fielding and S. P. Armes, J. Mater. Chem., 2012, 22, 11235–11244 RSC.
  24. Y. Chen, C. Wang, J. Chen, X. Liu and Z. Tong, J. Polym. Sci., Part A: Polym. Chem., 2009, 47, 1354–1367 CrossRef CAS.
  25. M. F. Haase, D. Grigoriev, H. Moehwald, B. Tiersch and D. G. Shchukin, Langmuir, 2011, 27, 74–82 CrossRef CAS PubMed.
  26. L. Tian, J. Yang, F. Ji, Y. Liu and F. Yao, J. Biomater. Sci., Polym. Ed., 2014, 25, 1573–1589 CrossRef CAS PubMed.
  27. F. J. Rossier-Miranda, K. SchroÃńn and R. Boom, Food Hydrocolloids, 2012, 27, 119–125 CrossRef CAS.
  28. D. Lee and D. A. Weitz, Adv. Mater., 2008, 20, 3498–3503 CrossRef CAS.
  29. M.-Y. Zhang, K. Xu, J.-H. Xu and G.-S. Luo, Crystals, 2016, 6, 122 CrossRef.
  30. A. F. Holleman and E. Wiberg, Lehrbuch der anorganischen Chemie, Walter de Gruyter, 1995 Search PubMed.
  31. S. Spirk, G. Findenig, A. Doliska, V. E. Reichel, N. L. Swanson, R. Kargl, V. Ribitsch and K. Stana-Kleinschek, Carbohydr. Polym., 2013, 93, 285–290 CrossRef CAS PubMed.
  32. W. Wei, L.-Y. Wang, L. Yuan, X.-D. Yang, Z.-G. Su and G.-H. Ma, Eur. J. Pharm. Biopharm., 2008, 69, 878–886 CrossRef CAS PubMed.
  33. H. Zhao, J.-H. Xu, P.-F. Dong and G.-S. Luo, Chem. Eng. J., 2013, 215–216, 784–790 CrossRef CAS.
  34. Z. An, H. MÃűhwald and J. Li, Biomacromolecules, 2006, 7, 580–585 CrossRef CAS PubMed.

Footnote

† These authors contributed equally to this work.
This journal is © The Royal Society of Chemistry 2016
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