Fabrication of mesoporous silica nanospheres with radially oriented mesochannels by microemulsion templating for adsorption and controlled release of aspirin

Abstract

Mesoporous silica nanospheres (MSNs) with radially oriented mesochannels were fabricated in a cetyltrimethylammonium bromide (CTAB)–ethanol–cyclohexane–water oil-in-water (O/W) microemulsion system at 35 °C by regulating ethanol-to-cyclohexane volume ratio. In addition, MSNs were obtained by introducing polyvinylpyrrolidone (PVP) as a stabilizing agent into the O/W microemulsion system. Compared with silica spheres prepared without PVP, the nanoparticle shape changed from slightly irregular spheroids to spheres, particle size decreased from 400–650 nm to 300–450 nm, and BET surface areas ranged from 1000–1114 m² g⁻¹ to 975–1052 m² g⁻¹. Based on the experimental results, a possible mechanism for the structural regulation of MSNs with radially oriented mesochannels prepared with or without PVP O/W microemulsion was proposed. Simple drug loading and release with aspirin as a model drug was performed to assess and compare the storage capacity and in vitro release profiles of the nanoparticles.

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1. Introduction

The rapid development of various applications has resulted in increased demand for mesoporous silica nanospheres (MSNs) with special structures and performance. Numerous reports on the preparation of MSNs have been published because of the multiple attractive intrinsic features of these nanoparticles, such as high surface area, high pore volume, and narrow pore-size distribution.^1–5 Aside from serving as supporting materials for drug delivery systems, MSNs exhibit widespread potential applications in enzyme immobilization, biomolecule separation, and confined-space catalysis because of their low density, good biocompatibility, thermal stability, and high mechanical stability.^6–14

To date, obtaining such MSNs with ordered mesochannels that are aligned perpendicular to the sphere surface and with good dispersity is difficult. A limited number of studies on the fabrication of MSNs with radially oriented mesochannels have been reported.^12,15–17 Chen et al. first reported the preparation of hollow mesoporous silica nanospheres (HMSNs) with radially oriented mesochannels in uniform shell (35 nm to 40 nm thick) using an anionic surfactant as template.¹² The product consisted of intact and dispersed hollow spheres with diameters mostly ranging between 100 and 500 nm, specific surface area of 502 m² g⁻¹ and average pore diameter of 3.1 nm. Teng et al. demonstrated a self-transformation approach to synthesize ordered HMSNs with radially oriented mesochannels by incubation with water.¹⁵ The obtained hollow spheres presented an average diameter of 550 nm and a mean shell thickness of approximately 110 nm. The mesochannels of the spheres were continuous throughout the shell, with openings at the surface, and were radially oriented toward the sphere surface. Compared with conventional MCM-41 and SBA-15, the radially oriented mesochannels in mesoporous silica spheres cause increased surface area and pore volume, which facilitate pore wall functionalization and interaction with various species. This effect is due to the possibility of combining the enormous functional variations of organic groups with the advantages of thermally stable and robust silica scaffolds.^6,12,18 On the other hand, radially oriented mesochannels allow for easy penetration of molecules into or out of the pore system.¹⁹ Kityk et al. presented a systematic optical polarimetry study aimed at exploring the orientational order of a discotic liquid crystal based on a pyrene derivative confined in parallel-aligned nanochannels of mesoporous alumina, silicon, and silica.²⁰ Thus, silica nanospheres with radially oriented mesochannels show potential in diverse applications such as in catalysis, adsorption, separation, and biomedicine, especially as multifunctional carriers in drug delivery. However, dense silica nanoparticles with radially oriented mesochannels reflected on the sphere from the spherical surface to the interior have never been seen before.

Microemulsions offer advantages in providing uniform nanospheres because of their transparency or translucency, low viscosity, isotropic and thermodynamically stable oil–water mixture systems.^21,22 MSNs have been successfully prepared through templating routes that use microemulsion systems.^22–25 Lin et al. reported the fabrication of spherical solids into hollow-structured silica nanoparticles, using a water-in-oil (W/O) microemulsion system formed from Triton X-100 (polyoxyethylene tert-octylphenyl ether)–hexanol–cyclohexane–water as template and aminopropyltrimethoxy silane with tetraethyl orthosilicate (TEOS) as silica source precursor. Solid silica nanoparticles with uniform size of approximately 40 nm were obtained, and the hollow silica nanospheres were approximately 40 nm in size with an internal diameter of 30 nm and wall thickness of around 5 nm. BET surface areas decreased from 280 m² g⁻¹ to 72 m² g⁻¹.²³ Moreover, Zhang et al. reported the formed process of magnetic colloidosomes by directing the self-assembly of SiO₂@Fe₃O₄ NPs and Fe₃O₄–SiO₂ hetero-nanorods at the interface of W/O droplets. These colloidosomes can be easily manipulated and self-aligned under an external magnetic field, thus presenting potential applications in microreactors, drug delivery, and other biomedical fields for their special magnetic response.²⁶

MSNs have been considered as excellent candidates for use in drug delivery systems for their tunable particle size, surface properties, shape, structure, and so on.^10,12,15 MSNs possess an open entrance to facilitate drug entry, as well as well-ordered channels for the homogeneous distribution of drug molecules.¹⁰ Wang et al. reported on HMSNs with radially ordered mesostructured. These HMSNs were validated by a drug release experiment with flurbiprofen, which exhibits higher storage capacity and significantly higher rate of release than flake-like mesoporous SBA-15 particles.¹² The effectiveness of the radially aligned mesopores facilitates rapid molecular transport and easy molecular accessibility. This property has a remarkable influence on high drug storage capacity and favorable molecular diffusion through the radially oriented mesopores for drug delivery.

The orderly alignment of mesopores perpendicular to the surface of the spheres presents an interesting material structure. Spherical radially oriented mesochannel MSNs were prepared by using O/W microemulsion as soft template. The method is relatively simple and effective for the fabrication of nanomaterials with good dispersity and to control the particle size. Synthesis of these sphere particles often involves the hydrolysis/condensation of TEOS around microemulsion droplets.²⁷ In the present study, MSNs with radially oriented mesoporous channels were prepared using an oil-in-water (O/W) microemulsion system, which consists of cetyltrimethylammonium bromide (CTAB), ethanol, cyclohexane and water as template, and TEOS as silica source. In addition, MSNs were also obtained in the presence of polyvinylpyrrolidone (PVP) as a capping agent and stabilizer in the O/W microemulsion system. The obtained MSNs possess controllable size, high surface area, and radially oriented mesochannels from the spherical surface to the interior. The application of prepared MSNs in drug loading and release was also investigated with aspirin as model drug.

2. Experimental section

2.1 Chemicals

Polyvinylpyrrolidone (PVP K30) was used as received from Sinopharm Chemical Reagent Co., Ltd. CTAB and tetraethoxysilane (TEOS) were obtained from Shanghai Chemical Reagent Inc. of Chinese Medicine Group. Ammonium hydroxide (NH₄OH) (25%), ethanol and cyclohexane were obtained from Tianjin Chemical Agent Co. (China). Aspirin (content > 98%) was purchased from Hebei Jingye Chemical Group Co., Ltd. All chemicals were of analytical grade and were used as received without any further purification.

2.2 Synthesis of MSNs using a microemulsion system

The procedure used to prepare the MSNs from microemulsion system using a positively charged CTAB as surfactant is as follows. TEOS was dispersed in cyclohexane by ultrasonication to form an oil phase. The oil solution and CTAB were then added to a mixture of water and ethanol, and ultrasonicated for 10 min to form a homogeneous O/W microemulsion. Thereafter, ammonium hydroxide was added into the solution to initiate reaction at 35 °C to promote TEOS hydrolysis. The molar ratio of the CTAB: cyclohexane: TEOS: ethanol: H₂O: ammonium hydroxide mixture was 1: (84, 126, 168, 211): 11: 1172: 6327: 30. After 4 h, the resulting products were collected by filtration, washed with water, dried at room temperature for 6 h and calcined at 550 °C for 6 h to remove organic components. The as-prepared silica samples were labeled as MSNsV1, MSNsV2, MSNsV3, and MSNsV4 at ethanol-to-cyclohexane volume ratios (R_V) of 7.5 (15 mL/2 mL), 5 (15 mL/3 mL), 3.75 (15 mL/4 mL), and 3 (15 mL/5 mL), respectively.

The same method as above was used to synthesize MSNs when PVP was added. The molar ratio of CTAB: PVP: cyclohexane: TEOS: ethanol: H₂O: ammonium hydroxide was 1: (0.005, 0.023, 0.046, 0.092): 168: 11: 1172: 6327: 30. Here, the molar ratio of cyclohexane to ethanol was 168: 1172. The as-prepared silica samples were labeled as MSNsM1, MSNsM2, MSNsM3, and MSNsM4 at PVP-to-CTAB mass ratios (R_M) of 0.5, 2.5, 5, and 10, respectively.

2.3 Aspirin adsorption and release

Drug storage and in vitro release profiles were obtained according to previously reported methods.^{2,11,12,28–31} The drug-loading process was conducted by immersing the MSNs (0.15 g) in 20 mL aspirin–ethanol solution at a specific concentration (20 mg mL⁻¹) and at room temperature. The mixture was stirred for 24 h at 25 °C to induce drug diffusion. Finally, the mixture was centrifuged at 6000 rpm for 10 min to obtain the aspirin-loading sample, which was dried at room temperature. The filtrate (0.5 mL) was obtained and properly diluted to 25 mL with ethanol, and then the adsorbed amount of aspirin was monitored using a Shimadzu UV-2600 spectrophotometer at 275 nm. The amount of drug adsorbed on the adsorbent was calculated based on mass balance before and after adsorption. After aspirin loading, the MSNs samples were labeled as MSNsV1-asp, MSNsV2-asp, MSNsV3-asp, MSNsV4-asp, MSNsM1-asp, MSNsM2-asp, MSNsM3-asp, and MSNsM4-asp, accordingly. The measurements were repeated thrice for each sample, and the results were averaged.

For release profiles, 100 mg of the loaded sample was placed in 50 mL phosphate buffer solution (pH 7.4). The contents were stirred at 300 rpm and at 37 °C. The sample (3.0 mL) was withdrawn immediately and replaced by another 3.0 mL of fresh phosphate buffer solution at each 30 min interval for the first 3 h, and eventually after every 1 h until the final measurement after 10 h. The aliquots were centrifuged to ensure that no solid particles were present in the suspension. The transparent supernatants were analyzed for aspirin using a UV-vis spectrophotometer at λ = 275 nm. The measurements were repeated thrice for each sample, and the results were averaged.

The loaded and released amounts of aspirin were calculated according to the method described in the authors' previous report.²⁸ Aspirin release (wt%) was assigned to aspirin released amounts (g)/total aspirin adsorbed amounts (g) in MSNs-asp. The drug loading content and encapsulation efficiency were calculated using the following equations:^32,33

2.4 Characterization

High-resolution transmission electron microscopy (HRTEM) observations were observed on JEM-2100 electron microscope with an acceleration voltage of 200 kV. All samples were dispersed in ethanol ultrasonically and were dropped on copper grids. Field emission scanning electron microscopy (FESEM) micrographs of samples were obtained with a Nova NanoSEM 450 microscope operated at an acceleration voltage of 10.0 kV. Sample powders were dispersed in ethanol by sonication, then dropped onto the surface of a silicon wafer and were sputter-coated for two cycles with gold to avoid charging under the electron beam prior to examination. N₂ adsorption–desorption experiments were measured on TriStar 3020 and QuadraSorb SI of Quantachrome Instruments. Samples were degassed for 6 h at 180 °C before measurements. Specific surface areas were calculated by BET (Brunauer–Emmett–Teller) method, the pore size distribution and volumes were calculated from the adsorption branch using BJH (Barett–Joyner–Halenda) methods. The N₂-adsorption experiments were replicated three times and the results were averaged. UV-vis spectra were recorded on a SHIMADZU UV-2600 spectrophotometer.

3. Results and discussion

3.1 Characterization of MSNs with radially oriented mesochannels

Fig. 1 and S1† show representative FESEM and HRTEM images of the morphology and particle size of the MSN products obtained at various ethanol-to-cyclohexane volume ratios, revealing radially oriented pore structures. Nearly irregular spheroids with mean diameter ranging from 400 nm to 650 nm were observed in the FESEM images (Fig. 1a and c, S1a, and S1c†). When 3 mL cyclohexane was added, the particle size decreased from 650 nm (MSNsV1) to 450 nm (MSNsV2). The contrast and distribution of dark and pale sections of the nanospheres indicate the existence of radially oriented mesopores in the HRTEM images (Fig. 1b and d, S1b, and S1d†).^15,34 When the amount of cyclohexane was further increased to 4 (MSNsV3) and 5 mL (MSNsV4), the particle size became 400 nm. The amount of cyclohexane exerted an effect on the particle size, which is relative to the size of the microemulsion droplet. However, novel MSNs with multiple cavities can be observed in the FESEM images (Fig. 1a and c), and the appearance of these cavities can be also found in the previous literature.^16,19 Sonicating the solution in the early stages of the reaction may have a large effect on breaking up the microemulsion droplets. In addition, silica oligomer hydrolysis and condensation around the microemulsion droplets is often too facile to be limited to the extremely small interfacial region.²³ Besides, the silica spheres undergo slight shrinkage during calcination, causing the appearance of cavities on the surface of MSNs.^6,16,19,34 The inset of HRTEM images (Fig. 1b and d, S1b, and S1d†) reveal radially oriented mesopores on the particle surface and inside the particle that are aligned along the normal direction of the particle surface and ran through from the spherical surface to the interior. The mesopore features were approximately 3.9 nm wide, which is consistent with the expected result from the cationic synthesis approach.^35,36

Fig. 1 FESEM (a and c) and HRTEM (b and d) images of MSNsV2 (a and b) and MSNsV4 (c and d). The insets are the corresponding magnified images of (b) and (d), respectively.

The effect of PVP-to-CTAB mass ratio on particle morphology and diameter was investigated. Fig. 2a–d and S2† display the HRTEM images of MSNs obtained in the presence of PVP. The significant feature of the spheres was their radially oriented pore structure from the center to the outer surface, which was approximately 4 nm in size was clearly observed in the inset of Fig. S2.† However, more reliable determination of the pore size may be obtained from nitrogen adsorption–desorption analysis.

Fig. 2 HRTEM images of MSNsM1 (a), MSNsM2 (b), MSNsM3 (c) and MSNsM4 (d).

The FESEM image (Fig. 3) shows that the prepared particles were intact spheres with a smooth surface without aggregation. MSNs prepared without addition of PVP (Fig. 1 and S1†) were slightly irregular spheroids in shape, with 400 nm to 650 nm average particle diameter. By contrast, monodispersed spherical nanoparticles with 300 nm to 450 nm diameter were obtained when PVP was added into the reaction system. Results show that PVP can be involved in and influence the morphology of silica particles. Silica particle sizes decreased when PVP was added, as compared with the silica spheres sizes prepared with only CTAB. Nanoparticles (MSNsM1) of around 450 nm in diameter were produced when 0.04 g PVP was added. In comparison, when the amount of PVP was increased to 0.2 g, the particle diameter decreased from 450 nm to 350 nm (MSNsM2). Upon further addition of PVP, the particle size became 300 nm and did not evidently change. In addition, the appearance of cavities can be observed in the FESEM images (Fig. 3).

Fig. 3 FESEM images of MSNsM1 (a), MSNsM2 (b), MSNsM3 (c) and MSNsM4 (d).

The N₂ adsorption–desorption isotherms of the MSNs (MSNsV1–4 and MSNsM1–4) products all show typical type-IV features with an adsorption step at relative pressure between 0.2 and 0.5 because of capillary condensation of the filling nitrogen in the mesopores (Fig. 4), thus indicating the presence of mesoporous channels.²⁴ The large H4-type hysteresis loop of MSNs in the P/P₀ range of 0.5 to 1.0 can be attributed to the presence of mesopores that have most probably resulted from particle packing.^27,37 Correspondingly, the pore size distribution was very narrow, with only one peak centered at about 4.0 nm in the pore size distribution curves of the desorption branch. This distribution indicates that 4.0 nm mesopores must be predominant in MSNsV1–4 and MSNsM1–4 samples. The spherical silica nanoparticles with radially oriented mesopores present micropores of about 1.4 nm (Fig. S3†). This conclusion is consistent with the result of the earlier literature.¹⁵ These micropores in the silica framework are crucial for facilitating the accessibility of guest molecules, such as drugs.^15,28 The pore size of each type of MSNs is uniform, regardless of particle size. The specific surface areas and pore volumes of the calcined MSNs were obtained for comparison, as shown in Table 1. Slight differences among MSNsM1, MSNsM3, and MSNsM4 were observed. On the other hand, MSNsM2 showed less surface area than MSNsM1, which decreased from 1052 m² g⁻¹ to 975 m² g⁻¹. The BET surface areas ranges were 1000 to 1114 (MSNsV1–4) and 975 m² g⁻¹ to 1052 m² g⁻¹ (MSNsM1–4), suggesting that these particles have larger surface areas than monomodal porous systems.^22,28 Except for MSNsV4, the pore volumes of MSNsV1, MSNsV2, and MSNsV3 exhibited an increasing trend. When the quantity of PVP was increased, the pore volume increased from 0.59 cm³ g⁻¹ to 0.74 cm³ g⁻¹. Moreover, with further increase in the amount of cyclohexane and PVP, the pore size showed no apparent change.

Fig. 4 The N₂ adsorption–desorption isotherms (a and c) and corresponding BJH pore size distribution curves (b and d) of MSNsV1–4 (a and b) and MSNsM1–4 (c and d).

Table 1 Physicochemical properties of the MSNs

Sample	RV	RM	SBET (m^2 g^−1)^a	V (cm^3 g^−1)^a	D (nm)^a
a D, SBET, and V stand for average BET pore diameter, surface area, and pore volume, respectively.
MSNsV1	7.5	—	1027	0.52	3.91
MSNsV2	5	—	1000	0.59	3.95
MSNsV3	3.75	—	1046	0.64	3.91
MSNsV4	3	—	1114	0.59	3.93
MSNsM1	3.75	0.5	1052	0.59	3.90
MSNsM2	3.75	2.5	975	0.61	3.95
MSNsM3	3.75	5	1031	0.70	4.07
MSNsM4	3.75	10	1035	0.74	4.07

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3.2 Mechanism for MSNs

A series of experiments was performed to investigate the growth of MSNs with radially oriented mesopores from the spherical surface to the interior. Understanding how the particles are formed is critical. A possible mechanism for the formation of MSNs with radially oriented mesochannels is illustrated in Scheme 1. In the microemulsion-based synthesis, cyclohexane is used as the oil phase, in which TEOS is dispersed to accelerate the hydrolysis reactions.²⁵ Short-chain alcohols are added to the microemulsions to render the surfactant films at the oil–water interfaces more flexible by lowering the bending moduli of the films, thus reducing the spontaneous curvature of the films.²² The sizes of the microemulsion droplets can be controlled by adding organic solvents as swelling agents. Cyclohexane is introduced into the synthesis solution to form initially as cores in the CTAB-stabilized O/W microemulsion.^17,38,39 When TEOS is mixed with the surfactant solution, the initial solubility of TEOS remains very poor until TEOS is hydrolyzed by ammonium hydroxide. The high concentration of organic solvents (cyclohexane and ethanol) in the homogeneous microemulsion system would slow down the hydrolysis reaction of TEOS to a large extent, so the size of MSNSV1 sample would be larger than the others.²² The positive-charged hydrophilic end of the surfactant dwells at the interface of water and oil droplets, whereas the hydrophobic long chain inserts into the droplet and keeps it stable.^22,24

Scheme 1 Schematic representation of the proposed assembly mechanism for the formation of MSNs.

First, numerous bead-like microemulsion droplets are produced, becomes interconnected compactly with one another, and self-aggregate into larger microemulsion rod-shaped aggregations.⁴⁰ Then, back-fence microemulsion droplets collide with other close droplets to crack, increasing the possibility of conglutination. This phenomenon leads to the formation of cylindrical microemulsions, which self-assemble and orient into positions perpendicular to the particle surface at the oil–water interface to form cylindrical microemulsion spheres.⁴¹ The process is similar to the formation of Ho/TiO₂ nanowires.⁴⁰ This mechanism reduces the high surface free energy caused by increased oil–water interfacial area. At the same time, the hydrolysis/condensation of TEOS occurs on the surface of the cylindrical microemulsion droplets, which simultaneously collide with other close particles.⁴¹ Finally, sphere-like SiO₂ is obtained by calcination to remove the organic components by leaving the radially oriented channels from the center to the surface. Given that the formation of the cylindrical microemulsion droplets is not an equilibrium process, the varying sizes of the cylindrical microemulsion droplets depend on the hydrogen bonds and van der Waals forces of the back-fence microemulsion droplets.²² The hydrolysis/condensation of TEOS on the surface of the cylindrical microemulsion droplets is restricted to the vicinity of the oil–water interface.²³ Thus, cavities are formed on the surface of the samples, as seen in FESEM images.

Notably, PVP was widely used as a stabilizer for the synthesis of colloids and nanoparticles.^42–46 In this study, PVP was added into the reaction system as capping agent and steric emulsion stabilizer. PVP molecular chain only possesses weak positive charge, but a ring opening reaction would be incited under alkaline conditions by adding a proper amount of ammonium hydroxide. Then, its molecular chain would become oppositely charged.⁴⁷ At this time, the oppositely charged PVP molecular chain associates with CTAB.^47,48 The PVP molecule chains were adsorbed on cylindrical microemulsion droplets, forming a continuous layer similar to a capping agent, to inhibit the growth of microemulsion droplets in all directions.^49,50 Thus, the dimension of mesoporous silica decreased because of the large restrictive power of PVP molecular chains.^51,52 As a result, the presence of the amount of PVP molecules could have stabilized the microemulsion droplets during the reaction and led to the formation of uniform smaller particles.^43,44

3.3 Drug adsorption and in vitro release

Previous studies have shown that the adsorption and release of drugs from different mesoporous silica materials are mainly diffusion-controlled with relation to particle size, BET surface areas, pore size, and the surface properties of mesoporous silica.^10,53–55 The N₂ adsorption–desorption isotherms for aspirin-loaded MSNs were obtained to measure their surface areas and pore volumes (Fig. S4†). Compared with parent MSNs, the surface areas of aspirin-loaded MSNs decreased approximately 37% to 43%, indicating that aspirin was successfully loaded into the MSNs pores. A corresponding decrease in the pore volume of aspirin-loaded MSNs relative to the parent MSNs by approximately 40% was also observed, which correlates to the presence of aspirin molecules inside the MSNs pores. MSNsM4 presents the highest drug loading capacity among the samples, which is attributed to its high BET specific surface area and the largest pore size.^6,10 The respective loading degrees of aspirin for MSNs and yield values are depicted in Table S1.† The drug loading content in MSNsM1–4 was efficiently increased when compared with that in MSNsV1–4 because of higher total pore volumes,¹⁰ whereas the encapsulation efficiency of aspirin in MSNsV1–4 was slightly larger than that in MSNsM1–4, as shown in Table S1.† This observation could be ascribed to the longer radially oriented mesochannels of MSNsV1–4 (400 nm–650 nm), whereas the length of the MSNsM1–4 channels is approximately 300 nm–450 nm. Aspirin contains a carboxylic acid group, which could interact favorably with the silanol groups on the surface of the samples by hydrogen bonding to promote the absorption of aspirin.⁵⁶ Besides, aspirin is adsorbed in regions near the pore entrance. Afterward, the pore will be clogged to limit further adsorption.

Apart from increasing the storage capacity of drug molecules, hierarchically porous spheres also can provide delivery pathways for drug molecule diffusion.^57–59 The aspirin release profiles of MSNs in phosphate buffer solution are shown in Fig. 5 and 6. The diffusion of drug molecules from the pores is largely dependent on the nature of the interaction of the drug molecule with the pore, as well as the intrinsic mobility of the drug molecules inside the pores.^10,60 The release data was similar with a first-order kinetic model involving an exponential decay, as described in the previous report.⁶¹

Fig. 5 The mean cumulative release rates of aspirin in MSNsV1-asp (■), MSNsV2-asp (●), MSNsV3-asp (▲) and MSNsV4-asp (▼).

Fig. 6 The mean cumulative release rates of aspirin in MSNsM1-asp (■), MSNsM2-asp (●), MSNsM3-asp (▲) and MSNsM4-asp (▼).

Fig. 5 suggests that the weak interaction (van der Waals interaction, hydrogen bonding) between aspirin molecules and the silanol groups on the surface contributed to the extensive release of aspirin in the initial stage.^56,62 Also, drug clogging in the pore entrance is one of the reasons for the rapid release rate.^11,62–64 Afterward, the aspirin delivery profiles showed a slow release, such that nearly 10 wt% of the adsorbed aspirin remained entrapped inside the mesopores. MSNsV3-asp showed a continuous rapid release rate compared with the relatively steady release rates of MSNsV1-asp, MSNsV2-asp, and MSNsV4-asp. The release profiles for MSNsV1-asp and MSNsV4-asp were similar, with approximately 80% maximum aspirin release after 7 h.

Fig. 6 suggests that all four samples (MSNsM(1 to 4)-asp) showed similar initial rapid rates of aspirin release, with nearly 40% of the aspirin released from the SiO₂ within the first hour. The amounts of aspirin released from MSNsM1-asp, MSNsM2-asp, MSNsM3-asp, and MSNsM4-asp after 7 h were 91 wt%, 93 wt%, 94 wt%, and 97 wt%, respectively, which indicates that the aspirin release rate increases with increasing amount of PVP. By contrast, the release time of aspirin decreased with increasing amount of PVP. Nearly complete release of aspirin was observed after 3 h for MSNsM4-asp. In general, slow sustained drug release is superior to relatively quick release.⁶ Compared with MSNsM1–4-asp, MSNsV1–4-asp exhibited a better aspirin release effect. The lower release rate of the MSNsV1–4-asp could be ascribed to the longer mesoporous channels of 450 nm to 600 nm in MSNsV1–4 samples than in MSNsM1–4-asp. Therefore, MSNsV1–4 samples with radially oriented mesopores can be advantageous in simulated concentrative release of drugs. The diffusion of drug molecules from the pores is largely dependent on the interaction of the drug molecule and the silanol groups. Modification on the surface of the mesoporous silica nanomaterials with organic groups is particularly interesting owing to the change in the forces between the silica nanomaterials with drug molecules. Typical strategies for immobilizing drug molecules via covalent bonds affect the drug release rate to reduce burst release and to achieve a more sustained release profile.^6,12 Future works will attempt to improve the interactions between drug molecules and the support system by modifying the surface of the radially oriented mesochannels in MSNs with organic groups to reduce burst release and achieve a more sustained release profile.

4. Conclusions

A simple and fast method of synthesizing MSNs with radially oriented mesochannels using an O/W microemulsion system at 35 °C was developed. The MSNs possess controllable size, high surface area, narrow pore size distribution, and the significant feature of the MSNs include the radially oriented mesochannels that ran through from the spherical surface to the interior. MSNsV1–4 samples with 400 nm to 650 nm average diameter were obtained by simple regulation of the volume ratio of co-surfactants ethanol and cyclohexane in the synthetic procedure. In addition, MSNsM1–4 samples of approximately 300 nm to 450 nm were obtained when PVP was added in to the reaction system and by simple regulation of the mass ratio of PVP and CTAB. In the reaction system, PVP has been explored as a capping agent and stabilizing agent to stabilize the microemulsion droplets during the reaction and led to the formation of uniform smaller particles. All samples had high surface areas of 1000 m² g⁻¹ to 1114 m² g⁻¹ (MSNsV1–4) and 975 m² g⁻¹ to 1052 m² g⁻¹ (MSNsM1–4). A plausible mechanism for the morphological regulation of MSNs was proposed. With the special mesoporous structure and high specific surface area, the integrated experimental and computational study of aspirin loading and release from MSNs indicated that MSNs with radially oriented mesochannels from the spherical surface to the interior have an open entrance for drugs to enter and release. Both MSNsV1–4-asp and MSNsM1–4-asp samples with radially oriented mesopores exhibited high aspirin loading (>32.7 wt% and >50.2 wt%, respectively). MSNsM1–4-asp exhibited higher rate of release (less than 6 h to reach the approximate maximal release amount) than MSNsV1–4-asp samples, indicating that MSNsV1–4 samples are more suitable for the molecular diffusion through the radially oriented mesopores.

Acknowledgements

This work was supported by the National Natural Science Foundation of China (Grant nos. 20976100, 51372124), the Natural Science Foundation of Shandong Province (Grant no. ZR2011BQ009), and the Program for Scientific Research Innovation Team in Colleges and Universities of Shandong Province.

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Footnote

† Electronic supplementary information (ESI) available: HRTEM Figures, FESEM Figures, N₂ adsorption–desorption isotherms, corresponding BJH pore size distribution curves after aspirin-loading, and structure parameters of different samples. See DOI: 10.1039/c4ra12291g

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