hydrophobic functional group initiated helical mesostructured silica for controlled drug release

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3834

DOI: 10.1002/adfm.200800631

Hydrophobic Functional Group Initiated Helical MesostructuredSilica for Controlled Drug Release**

By Lei Zhang, Shizhang Qiao,* Yonggang Jin, Lina Cheng, Zifeng Yan, and Gao Qing Lu*

In this paper a novel one-step synthetic pathway that controls both functionality and morphology of functionalized periodic

helical mesostructured silicas by the co-condensation of tetraethoxysilane and hydrophobic organoalkoxysilane using achiral

surfactants as templates is reported. In contrast to previous methods, the hydrophobic interaction between hydrophobic

functional groups and the surfactant as well as the intercalation of hydrophobic groups into the micelles are proposed to lead to

the formation of helical mesostructures. This study demonstrates that hydrophobic interaction and intercalation can promote the

production of long cylindrical micelles, and that the formation of helical rod-like morphology is attributed to the spiral

transformation from bundles of hexagonally-arrayed and straight rod-like composite micelles due to the reduction in surface free

energy. It is also revealed that small amounts of mercaptopropyltrimethoxysilane, vinyltrimethoxysilane, and phenyltrimethoxy-

silane can cause the formation of helical mesostructures. Furthermore, the helical mesostructured silicas are employed as drug

carriers for the release study of the model drug aspirin, and the results show that the drug release rate can be controlled by the

morphology and helicity of the materials.

1. Introduction

Self-assembly of molecules into helical architectures is

abundant in biology and synthetic analogs, such as the DNA

double helix,[1] peptides,[2] the triple helix of collagen,[3]

amphiphilic molecules,[4–7] and gemini surfactants.[8,9] In

recent years, fabrication of helically structured materials has

attracted great attention due to their potential applications

such as chiral selective separation, chiral recognition, and

enantioselective catalysis.[10–12] A rational design and synthesis

of helical mesostructured silica with controlled morphology

and helicity through surfactant self-assembly is an important

research topic but also very challenging.[13–22]

Che et al.[13–16] were the first to report the synthesis of chiral

mesoporous silica by a self-assembly of chiral anionic

[*] Dr. S. Z. Qiao, Prof. G. Q. Lu, L. Zhang, Y. G. Jin, L. ChengARC Centre of Excellence for Functional NanomaterialsSchool of Engineering and Australian Institute for Bioengineeringand NanotechnologyThe University of QueenslandBrisbane, QLD 4072 (Australia)E-mail: [email protected]; [email protected]

L. Zhang, Prof. Z. F. YanCollege of Chemistry and Chemical EngineeringChina University of PetroleumDongying 257061 (PR China)

[**] This work was financially supported by the Australian ResearchCouncil (ARC), UQ Middle Career Fellowship for S. Z. Q., and theARC Centre of Excellence for Functional Nanomaterials. L. Z. thanksthe China Scholarship Council (CSC) for offering a scholarship.Supporting Information is available online from Wiley InterScienceor from the author.

� 2008 WILEY-VCH Verlag GmbH &

surfactants and inorganic precursors. Later on, they found

that the macroscopic helices of aggregates were not always tied

to the molecular-scale chirality of their constituents, and

similar chiral mesoporous silica can also be formed using an

achiral surfactant such as sodium dodecyl sulfate as a template

and a quaternized aminosilane as a structure-directing

agent.[17] Recently, the synthesis of helical mesostructured

silicas using achiral cationic surfactants with the aid of

1-alkanol,[18] 1-aminoalkane,[18] ethyl acetate,[19] perfluoro-

octanoic acid,[20] or fluorinated surfactant[21] have been

reported. These findings further suggest that the inherent

chirality of the template molecule is not the sole driving force

in determining the chiral structure. Formation mechanism

studies by Yang et al.[20] and Meng et al.[21] have attributed the

origin of the helical rod-like morphology to the spiral

transformation from the bundles of hexagonally arrayed and

straight rod-like composite micelles due to the reduction in

surface free energy. However, they cannot explain the

transformation from the short composite micelles to straight

rod-like composite micelles and its driving force, which are

very important to explain the origin of helical mesostructures.

Quite recently, Han et al.[22] reported the formation of a helical

mesostructure by an entropically driven model.[23] They

proposed that the repulsive interaction between the ammo-

nium ions and the head groups of cationic surfactants made the

surfactant micelles impenetrable for the ammonia molecules,

and the surfactant micelles took on a helical conformation to

maximize the entropy of the system. However, the architec-

tural structures of the constituent molecules were not

considered. Moreover, their mechanism cannot explain the

transformation of morphology from spheres to straight rods

Co. KGaA, Weinheim Adv. Funct. Mater. 2008, 18, 3834–3842

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L. Zhang et al. /Helical Mesostructured Silica for Controlled Drug Release

with increasing the concentration of ammonia. It is interesting

to note that driving forces for the transformation from short

composite micelles to rod-like composite micelles and the

distortion of straight rod-like composite micelles are critical for

the understanding of the formation of the helical rod-like

morphology. Even with these achievements mentioned above,

the detailed mechanisms and controlling factors, as well as the

roles of the incorporated molecules that enable the formation

of straight rod-like composite micelles and chiral mesostruc-

ture, have not yet been fully understood.

The functionalization of mesostructured silica is particularly

attractive from the standpoint of materials scientists because of

the possibility to combine the enormous functional variations

of organic chemistry with the advantages of a thermally stable

and robust inorganic substrate, which is applicable to

biocatalysis,[24] separation and decontamination,[25] affinity

chromatography,[26] and drug delivery.[27] Co-condensation

(one-pot synthesis),[28] grafting (postsynthesis modifica-

tion),[29] and the imprint-coating method[30] are three typical

strategies for immobilizing functional groups onto mesoporous

silica via covalent bonds. The co-condensation of silicate with

various organoalkoxysilanes has been shown to yield materials

with a homogeneous spatial distribution of organic functional

groups covalently anchored to the pore walls.[28,31] Interest-

ingly, the presence of organoalkoxysilane precursors during

the base-catalyzed condensation greatly influenced the particle

morphology of the final products. By changing the precursor or

its concentration, the particle morphology was tuned to various

shapes including spheres, tubes, and rods of various dimen-

sions.[28,31] Such a synthetic pathway for both functionalization

and morphology controls could be tailored carefully so as to

enable the produced hybrid materials for various applications,

such as gatekeeping, drug delivery, and gene transfection.

Herein, we report a novel one-step synthetic pathway that

controls both functionality and morphology of functionalized

periodic helical mesostructured silicas by the co-condensation

of tetraethoxysilane (TEOS) and the hydrophobic organoalk-

oxysilanes 3-mercaptopropyltrimethoxysilane (MPTS), vinyl-

trimethoxysilane (VTMS), and phenyltrimethoxysilane

(PTMS) using achiral surfactants as templates (Scheme 1).

In this work, we not only synthesize functionalized helical

mesoporous silicas with controlled morphology and helicity,

but we also propose a new formation mechanism. We elaborate

on the transformation of the short micelles to helical cylindrical

composite micelles, and furthermore, we use the synthesized

materials as drug carriers to study the release of a model drug,

Scheme 1. The molecular structures of TEOS, MPTS, VTMS, and PTMS.

Adv. Funct. Mater. 2008, 18, 3834–3842 � 2008 WILEY-VCH Verl

aspirin. The results demonstrate that the drug release rate can

be controlled by the morphology and helicity of the helical

mesostructured silica.

2. Results and Discussion

2.1. MPTS Initiated Helical Mesostructure

Thiol functionalized helical mesostructured silica was

synthesized by the co-condensation of TEOS and MPTS using

hexadecyltrimethylammonium bromide (C16TAB) or octa-

decyltrimethylammonium bromide (C18TAB) as a surfactant,

withouttheuseofanyadditives.TheamountofMPTSwasvaried

from 0.0 to 0.1 g to investigate its effect on the formation of the

helical mesostructure. The products are denoted as MPTS-C16-x

(or MPTS-C18-x) where x stands for the amount of organoalk-

oxysilane added. Pure mesoporous silicas C16-0.00 and C18-0.00

were prepared as references[32] under the same experimental

conditions except that no organoalkoxysilane was added.

Transmission electron microscopy (TEM) images of the

surfactant-extracted samples synthesized by using either

C16TAB or C18TAB as a template are shown in Figures 1

and 2, respectively. It can be seen that the added amount of

Figure 1. TEM images of the samples synthesized with different amountsof MPTS using C16TAB. A) C16-0.0; B) MPTS-C16-0.05; C) MPTS-C16-0.08;D) MPTS-C16-0.10 (inset: cross-section images); E) MPTS-C16-0.10, takenat various tilt angles (�108, 08, 108, and 208) with the tilt axis parallel to therod axis.

ag GmbH & Co. KGaA, Weinheim www.afm-journal.de 3835

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Figure 2. TEM images of the samples synthesized with different amountsof MPTS using C18TAB. A) C18-0.0; B) MPTS-C18-0.02; C) MPTS-C18-0.05(inset: cross-section images); D) MPTS-C18-0.10; E) MPTS-C18-0.02, takenat various tilt angles (�408, �308, �208, �108, 08, 108, 208, 308, and 408)with the tilt axis parallel to the rod axis.

Figure 3. SEM images of helical mesostructured silicas A) MPTS-C16-0.05,B) MPTS-C18-0.02, C) MPTS-C16-0.10, and D) MPTS-C18-0.05.

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MPTS significantly affects the morphology of the materials.

When no MPTS is added, the product is spherical with a 60–

80 nm diameter (Figs. 1A or 2A). However, when a small

amount of MPTS (0.02–0.1 g) is added, the materials change

into helical mesostructured rods (Figs. 1B–E or 2B–E).

TEM images illustrate the intermittent appearance of lattice

fringes (corresponding to the spacing between the (10) planes

indicated by white arrows) along the rods with a constant

period, signifying the presence of chiral channels within

the helical rods for all MPTS-C16-x and MPTS-C18-x

samples.[13–22] The narrower and less obvious fringes observed

Table 1. Physical parameters of helical mesostructured silicas.

Sample name Particle length [nm] Particle diameter [nm]

C16-0.00 90–100 90–100

MPTS-C16-0.05 200–220 80–90

MPTS-C16-0.08 220–250 50–60

MPTS-C16-0.10 1000–2000 40–50

C18-0.00 100–110 100–110

MPTS-C18-0.02 180–200 80–90

MPTS-C18-0.05 1000–2000 40–50

MPTS-C18-0.10 1500–2000 30–40

VTMS-C16-0.13 220–250 50–60

PTMS-C16-0.05 180–200 50–60

VTMS-C18-0.05 200–230 50–60

PTMS-C18-0.02 200–220 60–70

www.afm-journal.de � 2008 WILEY-VCH Verlag GmbH

at the center between two neighboring (10) fringes correspond

to the (11) plane (indicated by dark arrows). The cross-section

images of MPTS-C16-0.10 and MPTS-C18-0.05 in Figures 1D

and 2C (insets) show well-organized mesopores packed in a

hexagonal symmetry.

The pitch of the helix (P), which is six times the distance

between the two sets of the (10) fringes, particle length and

diameter, length/diameter ratio, and pitch/diameter ratio of the

different rods were measured and are summarized in Table 1.

For the samples synthesized using the same surfactant as a

template, it is interesting to note that rod length increases,

whereas rod diameter and helical pitch decrease with an

increasing amount of MPTS. However, the rod shows a

constant pitch/diameter ratio of �9.5 for C16TAB and �6.5 for

C18TAB. TEM images (Figs. 1 and 2) and scanning electron

microscopy (SEM) images in Figure 3 show that the sizes of

helical mesostructured silica are quite uniform. Moreover, the

morphologies of MPTS-C16-0.05 and MPTS-C18-0.02 as well as

MPTS-C16-0.1 and MPTS-C18-0.05 are almost the same. Their

rod lengths and diameters are similar, but their helical pitches

are different.

Length/diameter ratio Pitch [nm] Pitch/diameter ratio

1 N/A N/A

2.2–2.8 800–820 �9.5

3.7–5 500–520 �9.3

20–50 410–430 �9.4

1.1 N/A N/A

2–2.5 550–570 �6.6

20–50 280–300 �6.4

38–67 220–240 �6.5

3.7–5 480–510 �9.0

3–4 500–520 �9.3

3.3–4.6 330–350 �6.2

2.8–3.7 390–410 �6.2

& Co. KGaA, Weinheim Adv. Funct. Mater. 2008, 18, 3834–3842

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Table 2. The physicochemical structural parameters of helical mesostructure

Sample name d100 [nm] [a] a [nm] [b]

C16-0.00 4.27 4.93

MPTS-C-0.05 4.17 4.81

MPTS-C16-0.08 4.05 4.68

MPTS-C16-0.10 3.82 4.41

C18-0.00 4.72 5.45

MPTS-C18-0.02 4.68 5.40

MPTS-C18-0.05 4.56 5.26

MPTS-C18-0.10 4.22 4.87

VTMS-C16-0.13 4.00 4.62

PTMS-C16-0.05 3.91 4.52

VTMS-C18-0.05 4.66 5.38

PTMS-C18-0.02 4.54 5.24

[a] The interplanar spacing of the (100) plane. [b] The lattice parameter calculated by a

pressure of P/P0¼ 0.05–0.25. [d] Pore volume, calculated by the N2 amount adsorbed

adsorption branch.

Figure 4. Small angle XRD patterns of samples synthesized using differentamount of MPTS. A) C16-0.0 (a), MPTS-C16-0.05 (b), MPTS-C16-0.08 (c),MPTS-C16-0.10 (d); B) C18-0.0 (a), MPTS-C18-0.02 (b), MPTS-C18-0.05 (c),MPTS-C18-0.10 (d).


Figures 1E and 2E show the TEM images of MPTS-C16-0.10

and MPTS-C18-0.02, respectively, taken at different tilting

angles. The tilt axis was parallel to the axis of the rod, thus the

rod was always perpendicular to the electron beam. With

sample tilting, the (10) planes at different positions along the

rod were sequentially turned to be perpendicular to the beam,

demonstrating the spiral nature of channels.[22] The (10) planes

appeared at the same position by a tube twist at 608, indicating

that the distance between the two sets of (10) fringes is one-

sixth of one pitch. The simulated image of a single-axis fiber

rotated at different angles and TEM images of the helical

mesostructured silica rotated at different angles (see Support-

ing Information, Fig. S1) confirm that the rod is composed of

chiral channels with a single twist axis,[13–22] and the chiral

direction is determined to be left-handed according to the

principle proposed by Terasaki et al.[14]

Small-angle X-ray diffraction (XRD) patterns of surfactant-

extracted samples synthesized using different amounts of

MPTS with C16TAB or C18TAB as a template are shown in

Figures 4A and B, respectively. A high-intensity diffraction

peak of (10) and three additional well-resolved diffraction

peaks of (11), (20), and (21) are observed, which can be

assigned to a 2D hexagonal mesostructure (space group

p6mm). This suggests a long-range ordering of the porous

structure and well-formed hexagonal pore arrays. For the

samples using C16TAB as a template, as the amount of MPTS

increases (sample C16-0.0, MPTS-C16-0.05, MPTS-C16-0.08,

and MPTS-C16-0.10), the four diffraction peaks shift to higher

angles, and the d-spacing calculated from the (10) peak are

4.27, 4.17, 4.05, and 3.82 nm (cell parameter a is 4.93, 4.81, 4.68,

and 4.41 nm), respectively. For the samples using C18TAB as a

template, a similar diffraction peak shifting can be observed.

The physicochemical parameters of all the samples are listed in

Table 2 for comparison.

Nitrogen sorption isotherms in Figure 5 show a type IV

curve with a well-defined capillary condensation step, thus

further confirming the existence of uniform channel-like

mesopores. The narrow and sharp pore-size distribution curves

silica.

S(BET) [m2 gS1] [c] V [cm3 gS1] [d] D(BJH) [nm] [e]

1203.2 1.18 2.58

1197.9 0.94 2.36

1136.1 0.77 2.06

1026.4 0.58 1.5

966.7 1.04 2.98

928.5 0.85 2.77

833.0 0.81 2.38

826.2 0.78 1.56

1140.3 0.75 2.03

1130.3 0.76 2.01

925.4 0.83 2.75

831.6 0.79 2.34

¼ 2d100=ffiffiffi

3p

. [c] BET surface area calculated using experimental points at a relative

at the highest P/P0 (�0.99). [e] Pore size, calculated by the BJH method using the


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Figure 5. N2 adsorption/desorption isotherms (insets: pore size distri-bution from adsorption branch) of samples synthesized using differentamount of MPTS. A) C16-0.0 (a), MPTS-C16-0.05 (b), MPTS-C16-0.08 (c),MPTS-C16-0.10 (d); B) C18-0.0 (a), MPTS-C18-0.02 (b), MPTS-C18-0.05 (c),MPTS-C18-0.10 (d). Isotherms of (a), (b), (c), and (d) in A and B have beenoffset by 500, 400, 300, and 200 cm3 g�1 along the vertical axis for clarity,respectively.

Figure 6. TEM images of samples synthesized using different amounts ofVTMS or PTMS. A) VTMS-C16-0.13; B) PTMS-C16-0.05; C) VTMS-C18-0.05;D) PTMS-C18-0.02.

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calculated by the Barrett–Joyner–Halenda (BJH) model

(insets in Fig. 5) suggest that the mesopores have very uniform

sizes. Their structural parameters are also summarized in

Table 2. For MPTS-C16-x samples, with an increasing amount

of MPTS from 0.0 to 0.1 g, the Brumauer–Emmett–Teller

(BET) surface area decreases from 1203.2 to 1026.4 m2 g�1, the

BJH pore diameter decreases from 2.58 to 1.5 nm and the pore

volume decreases from 1.18 to 0.58 cm3 g�1. Similar results

were also observed for MPTS-C18-x samples. Moreover, the

reduction in the pore diameter, pore volume, and specific

surface area confirms that the organic functional groups are

incorporated into the pore-wall network.[30]

2.2. VTMS-and PTMS-Initiated Helical Mesostructure

Vinyl and phenyl functionalized helical mesostructured

silicas were synthesized by a similar method to the synthesis of

thiol functionalized helical mesostructured silica through


co-condensation of TEOS and VTMS (or PTMS) using

C16TAB or C18TAB surfactant as a template. The products

are denoted as VTMS-C16-x and PTMS-C16-x (or VTMS-C18-x

and PTMS-C18-x) where x indicates the amount added of

organoalkoxysilane. TEM images of vinyl and phenyl

functionalized helical mesostructured silicas are shown in

Figure 6. The lattice fringes of (10) crystal planes (indicated by

white arrows) along the rods with a constant period confirm the

presence of chiral channels for all the VTMS-C16-0.13, PTMS-

C16-0.05, VTMS-C18-0.05, and PTMS-C18-0.02 samples.[13–22]

The particle length, particle diameter, length/diameter ratio,

pitch, and pitch/diameter ratio of different rods are summar-

ized in Table 1. It is interesting to note that samples MPTS-C16-

0.08 and VTMS-C16-0.13 synthesized by the organoalkoxysi-

lanes with different organic groups have similar rod length and

diameter, helical pitch, and pith/diameter ratio. The same

trend can be observed for samples PTMS-C18-0.02, MPTS-C18-

0.02, and VTMS-C18-0.05. This implies that the particle

morphology and helical pitch can be easily controlled by

adjusting the amount of organoalkoxysilane, and organoalk-

oxysilanes having different organic functional groups (MPTS,

VTMS, and PTMS) exhibit a similar effect on the self-assembly

of surfactant micelles and TEOS.

Small-angle XRD patterns of surfactant-extracted samples

with vinyl and phenyl functional groups synthesized using

C16TAB or C18TAB as a template are shown in Figures 7A and

B, respectively. Four diffraction peaks of samples VTMS-C16-

0.13, PTMS-C16-0.05, VTMS-C18-0.05, and PTMS-C18-0.02,

assigned to the (10), (11), (20), and (21) diffractions,

indicate a highly ordered 2D hexagonal mesostructure. Similar

to MPTS, with an increasing amount of VTMS or PTMS, the


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Figure 7. Small angle XRD patterns of samples synthesized using differentamounts of VTMS or PTMS. A) C16-0.0 (a), VTMS-C16-0.13 (b), PTMS-C16-0.05 (c); B) C18-0.0 (a), VTMS-C18-0.05 (b), PTMS-C18-0.02 (c).

Figure 8. N2 adsorption/desorption isotherms (insets: pore size distri-bution from adsorption branch) of samples synthesized using differentamounts of VTMS or PTMS. A) VTMS-C16-0.13 (a), PTMS-C16-0.05 (b); B)VTMS-C18-0.05 (a), PTMS-C18-0.02 (b). Isotherms of (a) in (A) and (B) havebeen offset by 200 cm3 g�1 along the vertical axis for clarity.

(10) diffraction peak shifts to a higher angle, and the d-spacing

and a value become smaller, which is attributed to the

hydrophobic interaction between the organic functional groups

of VTMS or PTMS and the surfactant.[30]

Nitrogen sorption isotherms of the samples are shown in

Figure 8. Similarly, the adsorption isotherms are typical of type

IV with a sharp capillary condensation step, which further

confirms the existence of uniform mesopores. The pore size,

pore volume, and BET surface area are listed in Table 2. The

calculated cell parameters and pore sizes of vinyl and phenyl

functionalized silicas are smaller than those of the pure silica

samples, which confirms that the organic functional groups

were incorporated into the pore-wall network.[30]

2.3. Elemental Analysis of Helical Mesostructured Silica

The elemental analysis of extracted helical mesostructured

silicas was used for quantitative determinations of various

functional groups in these materials. The helical mesostructured


silicas were washed by deionized water and extracted by

refluxing with ethanol for 8 h to remove the surfactant template

completely. Since all samples underwent the identical ethanol

extraction treatment, the extracted helical mesostructured

silica contained adsorbed ethanol at temperatures lower than

80 8C.[33] Before the elemental analysis, the samples were

degassed at 100 8C for 12 h in vacuo to remove adsorbed

ethanol. The initial molar percentages of functional groups in

MPTS-C16-0.10, VTMS-C16-0.13, and PTMS-C16-0.05 were 8.4,

13.7, and 4.4 mol%, respectively, which were calculated by using

the molar ratios of S/Si and C/Si in reactant silicon precursors

including TEOS and organoalkoxysilanes. The amount of

functional groups in the final products measured by element

analysis is generally less than that calculated theoretically due

to the different hydrolysis rates between the matrix precursor

and the functional silanes.[34] The percentages of functional

groups in MPTS-C16-0.10, VTMS-C16-0.13, and PTMS-C16-0.05

estimated by elemental analysis were 7.8, 13.0, and 4.3 mol%,

respectively. These results further confirmed that the


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terminal organic groups are incorporated into the pore-wall

network, and the proportion of terminal organic groups agrees

fairly well with the starting concentration of the reaction

mixture.

2.4. Formation Mechanism of Helical Mesostructure

The formation mechanism is illustrated in Scheme 2. In the

co-condensation reactions (NaOH solution, pH 11.7), the

trialkoxysilyl groups of these organoalkoxysilanes were

hydrolyzed and converted to hydrophilic trihydroxysilyl

groups. The hydrophilic or hydrophobic property of hydro-

lyzed organoalkoxysilanes was determined by the water

solubility of organic functional groups involved.[28] In our

system, the interaction between the hydrophobic groups of the

organoalkoxysilanes and the hydrocarbon tails of the alkyl-

trimethylammonium bromide molecules, and the intercalation

of the hydrophobic groups into the surfactant micelles, led to a

strong interconnection of individual short micelles to form

stable long rod-like micelles.[28] More importantly, the

reduction in surface free energy is the driving force for the

spontaneous formation of the spiral morphology, and the

transformation from a straight 1D rod-like composite micelle

to a helical one is more favorable than other possible

conformations because the curvature of one helix is a constant

at any point in space. Thus, the bending energy can be

homogeneously distributed within one individual rod-like

composite micelle, and the derivation from a perfect hexagonal

mesostructure can be minimized.[20,35]

The organization of the trialkoxysilyl group at the Gouy–

Chapman region of the surface of micelles can assist in the

rapid crosslinking/condensation between individual rod-like

micelles in a basic aqueous solution to produce bundles of rod-

like composite micelles.[28] The residual silica-surfactant

complexes then react preferentially with the surface silanols

of the particles that have been generated, preventing the

formation of any extra particles. This leads to the formation of

uniform helical mesostructured silica rods.

To test the proposed mechanism, we used 3-aminopropyl-

triethoxysiliane (APTMS) or N-(2-aminoethyl)-3-aminopro-

pyltriethoxysiliane (AAPTMS) as co-precursors to carry out the

Scheme 2. Synthetic mechanism of functionalized helical mesostructured s


synthesis. We found that only spherical silicas with well-defined

hexagonal mesostructures are obtained (see Supporting

Information, Figs. S2 and S3). The reason is that the hydrophilic

amino groups of APTMS or AAPTMS in the aqueous

solution limit the intercalation of organic groups of the

organoalkoxysilane into micelles. Therefore, it is impossible

toproduce long micellesandhelicalmesostructuresaccordingto

our proposed mechanism. In our experimental observation

(Figs. 1 and 2), the decrease in pore sizes and the transformation

of morphology from a sphere to a helical mesostructured

rod with the addition of the organoalkoxysilane with hydro-

phobic groups further confirm the effect of hydrophobic

interaction.

We also found that as the amount of organic functional

groups increase, the effect of hydrophobic interaction increase,

which then leads to the formation of longer rod-like products

with much more twisted helical mesostructures. For example,

with an increase of MPTS from 0.0 to 0.10 g (samples C16-0.0,

MPTS-C16-0.05, MPTS-C16-0.08, and MPTS-C16-0.10 or

C18-0.0, MPTS-C18-0.02, MPTS-C18-0.05, and MPTS-C18-

0.10), the pitch of the samples decrease and the length of

the particles increase significantly (Figs. 1 and 2, Table 1).

The order of hydrophobicity of organic functional groups is

PTMS�MPTS>VTMS.[36–39] The samples of PTMS-C16-

0.05, MPTS-C16-0.08, and VTMS-C16-0.13 (or PTMS-C18-0.02,

MPTS-C18-0.02, and VTMS-C18-0.05) have the same morphol-

ogies and helical mesostructures. The amount of added organic

functional groups is consistent with their hydrophobic ability.

That is, a smaller amount of more hydrophobic and bulky

organic groups are needed to achieve a similar morphology and

helicity. This observation further confirms our proposed

mechanism.

It is worthy to note that sample MPTS-C16-0.05 is similar to

MPTS-C18-0.02 in terms of particle morphology (Figs. 1 and 2,

Table 2). This could be explained by the difference in

stiffness between the C16TAB and C18TAB micelles.[22]

C16TAB molecules are more rigid than C18TAB due to their

shorter hydrocarbon chain, making the rod-like micelles

more difficult to bend into a helix. Therefore, a higher

concentration of hydrophobic groups (MPTS) was needed

in the C16TAB system compared to the C18TAB to

achieve similar morphologies. Similar results were found with

ilicas.

& Co. KGaA, Weinheim

MPTS-C16-0.1 and MPTS-C18-0.05, VTMS-

C16-0.13 and VTMS-C18-0.05, and PTMS-

C16-0.05 and PTMS-C18-0.02.

2.5. Controlled Drug Release on Helical

Mesostructured Silica

Mesoporous materials are promising car-

riers in controlled drug-delivery systems due

to their high surface area, well defined and

tunable pore size, uniform porous structure,

good dispersibility in aqueous solution,

easily modified surface properties, and

Adv. Funct. Mater. 2008, 18, 3834–3842

FULLPAPER


Figure 9. Release kinetics of aspirin loaded on samples A) MPTS-C18-0.05,B) MPTS-C16-0.05, and C) C16-0.00 in PBS buffer.

biocompatibility.[40–46] When mesoporous materials are used in

drug delivery, the release can be effectively controlled on the

basis of physical and morphological properties of the materi-

als.[44–46] It may be expected that the twisted channel of the

helical mesostructured silica with varying morphology and

helicity can achieve a controlled drug release.

To investigate helical mesostructured silica as a controlled

drug release carrier, we selected calcined samples C16-0.00,

MPTS-C16-0.05, MPTS-C18-0.05 with different morphology

and helicity but similar pore size as drug hosts, aspirin as the

model drug, and phosphate buffer solution (PBS) as the release

media. The loadings of aspirin in C16-0.00, MPTS-C16-0.05, and

MPTS-C18-0.05 were 18, 16, and 16 wt%, respectively. To

measure the amount of released aspirin, the helical mesos-

tructured silica in PBS was captured by using centrifugation.

Figure 9 shows the drug release profiles in PBS for C16-0.00,

MPTS-C16-0.05, and MPTS-C18-0.05 loaded with aspirin.

Adsorbed aspirin (70%) is released from C16-0.00 within

60 h, while MPTS-C16-0.05 and MPTS-C18-0.05 can delay the

release of aspirin. For example, 52% of adsorbed aspirin is

released from MPTS-C18-0.05 after 60 h of incubation. Mean-

while, the slope of the drug release curves in Figure 9 shows the

order of the release rates of aspirin as C16-0.00>MPTS-C16-

0.05>MPTS-C18-0.05. Since the three samples have a similar

pore size, the variable release profiles may be attributed to

the difference of morphology and helicity. It is observed that

the morphology of C16-0.00 is spherical with a 90–100 nm

diameter, MPTS-C16-0.05 is a rod 200–220 nm in length and 80–

90 nm in diameter, while MPTS-C18-0.05 is a longer and thinner

rod (1000–2000 nm in length and 40–50 nm in diameter).

Moreover, channels of MPTS-C16-0.05 and MPTS-C18-0.05 are

helical mesostructures with 800–820 nm and 280–300 nm in

pitch, respectively. The short and straight diffusion channel of

C16-0.00 leads to the fastest release rate among three samples.

Compared with MPTS-C16-0.05, longer and more twisted

diffusion channels of MPTS-C18-0.05 are a key reason for its

slowest release rate. These results demonstrate that the drug

release rate can be controlled by the morphology and helicity

of the helical mesostructured silica.


3. Conclusions

This work is the first report of a one-step synthetic pathway

that controls both functionalities and morphology of function-

alized periodic helical mesostructured silicas by the co-

condensation of TEOS and hydrophobic organoalkoxysilane

using achiral surfactants as templates. The morphology and

pitch of helical mesostructured silica can be controlled by

simply varying the amount of added organoalkoxysilane. The

hydrophobic interaction between hydrophobic functional

groups and the surfactant as well as the intercalation of

hydrophobic groups into the micelles are proposed to lead to

the formation of helical mesostructures. Our study also

demonstrates that this hydrophobic interaction and intercal-

ation can promote the formation of long cylindrical micelles

and the formation of helical rod-like morphology is attributed

to the spiral transformation from bundles of hexagonally

arrayed and straight rod-like composite micelles due to the

reduction in surface free energy. Drug release results reveal

that the release rate can be controlled by the morphology and

helicity of the helical mesostructured silicas. Highly ordered

periodic mesopores, functionalized surfaces, and helical

structures of these novel materials are very promising for

drug delivery, selective separation, selective recognition, and

enantioselective catalysis. The synthetic strategy and forma-

tion mechanism developed in this work may be helpful for the

design and synthesis of unique helical mesostructured

materials and may assist in the understanding of the production

of helical tunnels and morphologies.

4. Experimental

Synthesis: TEOS (99%), C16TAB (95%), C18TAB (97%), VTMS(98%), MPTS (99%), sodium hydroxide (98%), and PTMS (98%) werepurchased from Aldrich. All chemicals were used as received withoutpurification.

Helical mesostructured silicas were synthesized under basicconditions using C16TAB (or C18TAB) as surfactant micellartemplates, and TEOS and organoalkoxysilane (such as MPTS, VTMS,and PTMS) as co-condensed precursors. In a typical synthesis, 0.20 g ofC16TAB (or C18TAB) was dissolved in 96 g of deionized water understirring at room temperature. Then 0.70 mL of NaOH (2 M) was addedinto the solution. The temperature of the solution was raised to 80 8C.To this clear solution, TEOS (1.15 g) and a desired amount oforganoalkoxysilane (MPTS, VTMS, or PTMS) were added sequen-tially and rapidly via injection. A white precipitate was observed after3 min of stirring at �550 rpm. The mixture was continuously stirred foran additional 2 h. For all experiments, the resulting powders werewashed using deionized water and extracted by refluxing with ethanolat 60 8C for 8 h to remove the surfactant templates completely. Theresulting products were collected by filtration and dried at roomtemperature.

Loading and Release of Drug: 0.1 g of helical mesostructured silica(the products were calcined at 550 8C for 6 h to completely remove thesurfactant templates and organic functional groups) were added into12 mL of 20 mg mL�1 aspirin solution in anhydrous ethanol. Themixture in a sealed vial was dispersed by ultrasonication for 30 min andshaken at room temperature at 200 rpm for 72 h. The helicalmesostructured silicas incorporated with aspirin were collected by


FULLPAPER


3842

centrifugation and washed with water, then dried in an oven at 50 8C.The amount of drug loaded in the pores of the carrier was characterizedquantitatively using a thermogravimetric analyser (TGA). A fullydried sample was suspended into 10 mL of sodium phosphate buffer(100 mM, pH 7.4), and dispersed by ultrasonic treatment for 10 min. Therelease experiment was carried out at 37 8C. At a given time, the samplewas collected by centrifugation, and the solution was carefully removedfor the measurement of released drugs into the solution. The content ofaspirin in solution was measured by UV-vis absorbance at 296 nm.Three parallel experiments were carried out for each experiment pointto provide error bars.

Characterization: XRD measurements were performed on aRigaku D/max-2550V diffractometer using Co Ka radiation at30 kV and 15 mA. SEM images of samples coated with platinum wererecorded on a JEOL 6300 microscope. TEM images were obtained byFEI Tecnai F30 electron microscope. The powder samples for the TEMmeasurements were suspended in ethanol and then dropped ontocopper grids with porous carbon films. Nitrogen sorption isotherms ofsamples were obtained by a Micromeritics TriStar 3000 analyzer at77 K. Before any measurements were taken, the samples were degassedat 150 8C for 12 h under vacuum. The BET surface area was calculatedusing experimental points at a relative pressure of P/P0¼ 0.05–0.25.The total pore volume was calculated by the N2 amount adsorbed at thehighest P/P0 (P/P0� 0.99). The pore size distribution was calculated bythe BJH method. Elemental analysis of the prepared material wascarried out by an Eager 300 CHNS Analyzer. An UV-vis absorbancespectrophotometer (JASCO-V550) was used to determine theconcentration of aspirin in supernatant solution at 296 nm.

Received: May 6, 2008Revised: September 9, 2008

Published online: November 10, 2008

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hydrophobic functional group initiated helical mesostructured silica for controlled drug release

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