7498 Chem. Commun., 2010, 46, 7498–7500 This journal is c The Royal Society of Chemistry 2010

Novel fluorinated polysilsesquioxane hollow spheres: synthesis and

application in drug releasew

Fuping Dong, Wanping Guo, Sang-Wook Chu and Chang-Sik Ha*

Received 31st May 2010, Accepted 2nd September 2010

DOI: 10.1039/c0cc01658f

Fluorinated polysilsesquioxane (FPSQ) hollow spheres with a

large empty interior were synthesized in an aqueous medium by

using (trifluoropropyl)trimethoxysilane as the sole precursor.

The drug release applications of these spheres were demonstrated,

and the materials have great potential as fluorinated drug release

carriers.

Hollowmicro/nanostructured materials have attracted increasing

interest for their potential applications as nanoparticle collectors,

efficient catalysts, and drug-delivery carriers because of their

empty interior.1,2 These materials include both organic hollow

materials, such as polymer capsules,3,4 and inorganic hollow

materials, such as one-dimensional nanotubes5,6 or silica

hollow spheres.7–9 However, very few studies have examined

organic–inorganic hybrid materials with hollow structures.

Hah et al. investigated phenyl-functionalized hollow poly-

silsesquioxane (PSQ) particles,10 and Yuan et al. prepared

thiol-functionalized hollow polysilsesquioxane spheres11 with

a general formula of [RSiO1.5]n for PSQs, where R is an

organic group.12 Regardless of the hollow structure, some

polysilsesquioxane hard spheres, with functional groups

including mercapto, amine, vinyl, acrylic or isocyanate, have

been synthesized.13,14 This type of organic–inorganic molecular-

level hybrid polymers has many unique properties, which

traditional composite materials do not exhibit.15

Fluorinated functional materials exhibit satisfactory

performances in the fields of sensing, catalysts, biology and

environmental protection thanks to their unique properties,

such as low surface energy, high contact angle, reduced

coefficients of friction, and hydrophobicity.16 In particular,

fluorinated silicon-based materials are useful in many applications

because of the unusual chemical and physical properties that

are imparted by fluorine for these organic–inorganic nano-

composites.17 Some studies have shown that the introduction

of fluorine onto silica can meet versatile requirements.

Johnston and co-workers grafted perfluorodecane side chains

onto silica surfaces and successfully stabilized a nondilute

silica dispersion in liquid carbon dioxide at 25 1C and at the

vapor pressure.18 Otsuka et al. used a fluorocarbon modified

silica as a drug carrier to improve the drug recovery efficiency

from phytonadione-loaded silica gels.19 Nie’s group used

(trifluoropropyl)triethoxysilane (TFPTES)/tetraethyl orthosilicate

(TEOS) mixed precursors to prepare fluorine-modified silica

membranes with a high hydrothermal stability for hydrogen

separation.20 However, the post-modification of silica usually

requires more complicated processing steps, such as additional

coupling reactions under heating, and obtaining monodispersed

particles is difficult due to aggregation, whereas TFPTES/

TEOS mixed precursors lead to a limited fluorine-content in

the materials.

The amount of functional groups on the surfaces of hollow

structured materials directly affects the materials’ properties

and applications.6 Until now, the synthesis of fluorinated

polysilsesquioxane hollow spheres with a high surface coverage

still remains a challenge.

In this communication, fluorinated polysilsesquioxane

hollow spheres were prepared for the first time, and their

applicability in drug release systems was demonstrated. The

FPSQ hollow spheres were synthesized directly via the hydrolytic

polycondensation in aqueous solution. The hollow spheres not

only had a high surface coverage of the fluoroalkyl group

(theoretically, 6.71 mmol g�1), but also had a typical particle

size of 192 � 12 nm, which is quite suitable for many

applications, especially for controlled drug release systems.21

An example of the drug release was demonstrated using these

FPSQ hollow spheres as the drug carrier. The in vitro drug

release studies demonstrated that a steady release process was

obtained for the fluorinated drug using this carrier.

The fabrication procedure consists of two steps: the synthesis

of a polystyrene (PS) template and the growth of the poly-

silsesquioxane shell on the polymer surface as shown in

Scheme 1 (see the ESIw for the detailed procedure). In the

first step, polyvinylpyrrolidone (PVP)-modified PS beads were

prepared through an emulsifier-free emulsion polymerization

in an aqueous medium.22 The scanning electron microscopy

observations (Fig. 1a) demonstrated that the as-prepared PS

spheres had an approximate size of 140 � 10 nm, with a very

narrow distribution. In the second step, different amounts

(0.5 to 4.5 mL) of ammonia were added into the PS suspension,

and then the (3,3,3-trifluoropropyl)trimethoxysilane (FTMS)

precursor was added very slowly dropwise into the mixture.

The fluorinated polysilsesquioxane shell grew on the PS

surface through a hydrolytic condensation process. As shown

in the SEM images and DLS data (Fig. 1b–f), the as-prepared

products maintained a spherical morphology with an average

diameter of around 200 nm in a narrow size distribution

Scheme 1 Preparation of the fluorinated polysilsesquioxane hollow

spheres and their application in a drug release process.

Department of Polymer Science and Engineering,Pusan National University, Busan, 609-735, Korea.E-mail: csha@pusan.ac.kr; Fax: +82-51-514-4331;Tel: +82-51-510-2407w Electronic supplementary information (ESI) available: Experimentalprocedures and additional data. See DOI: 10.1039/c0cc01658f

COMMUNICATION www.rsc.org/chemcomm | ChemComm

This journal is c The Royal Society of Chemistry 2010 Chem. Commun., 2010, 46, 7498–7500 7499

regardless of the amount of ammonia, although the size of the

spheres was slightly increased with increasing the amount of

ammonia.

Fig. 2a shows the TEM image of the samples that were

prepared using 3.5 mL of the ammonia solution. A noticeable

contrast between the black margin and the bright center

confirmed the existence of the hollow structure in the resulting

spheres. Fig. 2b gives the typical TEM image of an individual

particle, which exhibited an average diameter of 180 nm and a

shell thickness of 25 nm. The hollow spheres were formed and

the PS latexes were dissolved subsequently or even synchronously

into the ammonia solution under current concentration, which

is consistent with a previous report.7 Fig. 2c shows the N2

adsorption–desorption isothermal plot of the FPSQ hollow

spheres. An H2-type hysteresis was observed at higher

pressures (P/P0 of 0.8–1), indicating that some macropores

were present on the shell of the hollow spheres. This sample

was further characterized and used for the drug release

experiments. The shell thickness of the sample could be

controlled by decreasing or increasing the amount of the

FTMS precursor (Fig. S1, ESIw).In the 29Si NMR spectrum of FPSQ, only one peak

appeared at �71.5 ppm, indicating the fully condensed Si

atoms of the SiO1.5 unit in the structure of the materials

(Fig. 2d).23 The spheres were also characterized using FTIR

spectroscopy (Fig. 3a), which showed that almost all of the PS

templates were removed from the hollow spheres through the

disappearance of a few characteristic peaks at 1452, 761, and

697 cm�1. The FTIR spectrum also confirmed the formation

of the Si–O–Si bonds (1132, 1070 cm�1), Si–C bonds

(1272 cm�1) and the CF3 groups (1319, 1225 cm�1).24 An

energy dispersive X-ray (EDX) spectrometer was used to

analyze the nature and the elemental composition of the

specimens. The EDX results revealed a high level surface

element F (Fig. S2, Table S1, ESIw).The formation of the fluorinated polysilsesquioxane hollow

spheres relies on the hydrolysis and polycondensation reactions.

It is generally considered that the silsesquioxanes tend to form

three Si–O–Si bonds, and the cyclization reactions play an

important role in the polymerization process, which result in

the polysilsesquioxanes containing cage-like structure.25,26 On the

other hand, the uncontrolled hydrolysis of organosilica precursor

with excess of water could finally produce some random network

macromolecule in the system. Just as shown in the IR spectrum

(Fig. 3a), the strong absorption peaks at 1132 cm�1 and

1070 cm�1, indicated by arrows, represent the cage-like and the

network structure, respectively.27 Fig. 3b displays the XRD

pattern with two halos at 8.61 (d = 1.03 nm) and 20.61

(d = 0.43 nm) which was thought to be related to the ladder-

like double chain.28 Based on the above discussion, it seems that

the fluorinated polysilsesquioxanes may be composed of a

mixture of cage-like, random network and ladder-like structures.

Two types of fluorinated drugs (5-fluorouracil (5-FU),

flucytosine) and one type of non-fluorinated drug (captopril)

were loaded as the model molecules in order to investigate the

capability of the FPSQ hollow spheres as drug carriers. The

FPSQ hollow spheres were immersed in an aqueous drug

solution with vigorous stirring to make sure the drugs diffused

into the carriers. The release experiments were performed in

30 mL of a PBS solution at pH 7.4 and 37 1C (Fig. 4).

During these experiments, 11% 5-FU and 27% flucytosine

were released in 1 h. However, for captopril, about 81% of the

drug was released in one hour. The profiles also showed that

5-FU and flucytosine were released slowly over 24 h. These

results demonstrated that the FPSQ hollow spheres provided a

slow release when the fluorinated drug was loaded, while

an initial fast release was observed when non-fluorinated

drug was loaded. The fluorophilic attraction between the

fluorinated drug and the fluorinated PSQ carrier surface may

play an important role in the release process,29–31 although the

mechanism is still being studied.

Fig. 1 SEM images of (a) the PS latexes and the FPSQ spheres with

various amounts of ammonia: (b) 0.5, (c) 1.5, (d) 2.5, (e) 3.5, (f) 4.5 mL.

The insets are the size distribution histograms that were measured

using DLS in aqueous solution. The amount of FTMS was 1.09 g in all

of the above formulations. The scale bars are 100 nm.

Fig. 2 TEM images of (a, b) the FPSQ hollow spheres with 3.5 mL of

the ammonia solution (the same sample as Fig. 1e, the scale bars are

100 nm); (c) nitrogen adsorption–desorption isotherm corresponding

to (a) and (b); (d) 29Si NMR spectrum of the FPSQ hollow spheres.

Fig. 3 (a) FTIR spectra of PS latexes and FPSQ hollow spheres;

(b) XRD pattern of the FPSQ hollow spheres.

7500 Chem. Commun., 2010, 46, 7498–7500 This journal is c The Royal Society of Chemistry 2010

In summary, new fluorinated polysilsesquioxane hollow

spheres were prepared and used for drug release. The mono-

dispersed FPSQ hollow spheres had a high fluoroalkyl coverage

surface and an empty interior, providing these materials with

some potential applications, such as catalysts, gas separation,

coating materials, nanoreactors and so on. The in vitro drug

release experiments demonstrated that the hollow FPSQ

spheres could potentially be applied as release carriers for

fluorinated drugs.

The work was supported by the National Research

Foundation of Korea (NRF) Grant funded by the Ministry of

Education, Science and Technology, Korea (MEST) (Acceleration

Research Program (No. 20100000790); Pioneer Research Center

Program (No. 2010-0019308/2010-0019482)), a grant from the

Fundamental R&D Program for Core Technology of Materials

funded by theMinistry of Knowledge Economy, Korea, and the

Brain Korea 21 Project of the MEST.

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Fig. 4 Release profiles of the different drugs from the FPSQ hollow

spheres in a PBS solution at 37 1C.