This journal is c The Royal Society of Chemistry 2011 Chem. Commun., 2011, 47, 10001–10003 10001

Cite this: Chem. Commun., 2011, 47, 10001–10003

Formation of organic nanoparticles by solvent evaporation within porous

polymeric materialsw

Lei Qian, Adham Ahmed and Haifei Zhang*

Received 14th June 2011, Accepted 21st July 2011

DOI: 10.1039/c1cc13509k

A simple and generic method is developed to form organic

nanoparticles in porous materials by solvent evaporation. The

composites can be readily dissolved in water to produce aqueous

organic nanoparticle dispersions.

Synthesis of nanoparticles has been extensively investigated

due to their unique properties. Among them, metal nanoparticles

and inorganic nanoparticles have been mostly studied while not

much attention has been paid to organic nanoparticles. In recent

years, organic nanoparticles have been synthesized and investigated

for potential applications in the fields of optoelectronics, nonlinear

optics and phonics.1 A large percentage of pharmaceuticals and

agrochemicals are poorly water soluble.2 This leads to low

bioadsorption and limited therapeutic efficacy. To address

this problem, pharmaceutical nanoparticles are prepared to

increase solubility in water because the dissolution rate of the

organics is proportional to the surface area available for

dissolution.3 However, the barrier to the synthesis of organic

nanoparticles is that most organic compounds are thermally

fragile and thus mild preparation conditions are required.4

Organic nanoparticles may be synthesized by a top-down

approach or a bottom-up approach.1,5 For the top-down

approach, large organic particles can be processed by milling,

grinding, homogenization, laser ablation, or a ‘PRINT’

method.2,5–7 However, it is very difficult to produce nanoscale

particles and the particles tend to aggregate. The bottom-up

approach employs organic solutions to build nanoparticles

from molecules. The most widely used route has been repre-

cipitation via the use of organic solutions or emulsions.1,5,8,9

The concentrated dispersions of organic nanoparticles can be

prepared by direct condensation of an organic material into a

liquid. However, this method may be only limited to thermally

stable compounds.10 Recently, chitosan solutions were pumped

into a receiver solution through a nanoporous membrane

to produce chitosan nanoparticles by adjusting pH.11 Self-

assembly of polycyclic molecules in organic solutions has been

widely employed to produce molecular materials12 while

ordered nanowires or surface patterns have been fabricated

by controlled solvent evaporation on a flat surface.13

The stability of nanoparticles is a big issue when the

nanoparticles are formed directly in a liquid. Recently,

we developed a new method of emulsion freeze-drying to

produce porous organic nanoparticles–polymer composites.

The formed composites could be dissolved in water instantly

to form stable aqueous nanoparticle dispersions.14 However,

there are limitations to this method: (1) a relatively stable

oil-in-water (O/W) emulsion needs to be formed first; (2) the

involved organic solvents should be suitable for a freeze-

drying process, i.e., with relatively high melting points.

It should be noted that many organic compounds are water

insoluble but soluble in polar organic solvents such as acetone

or ethanol. However, it is very difficult to form an O/W

emulsion with acetone or ethanol and the low melting points

of both solvents (below �90 1C) mean that it is not practical to

freeze dry such emulsions.

To address these issues, we reported here the use of pre-

formed porous materials as the scaffolds for the preparation of

porous organic nanocomposites by solvent evaporation and

the subsequent formation of aqueous nanoparticle dispersions.

Scheme 1 Schematic representation for the preparation of water-

dispersed organic nanoparticles. A porous material (top left image,

empty circles representing pores while grey background for the

polymer matrix) is firstly prepared and then soaked into an organic

solution. The organic solvent is removed from the soaked sample by

evaporation with the in situ formation of organic nanoparticles. The

composite material can be dissolved in water to produce aqueous

organic nanoparticle dispersion.

Department of Chemistry, University of Liverpool, Liverpool, L69 7ZD,UK. E-mail: zhanghf@liv.ac.uk; Fax: +44 (0)151 7943588;Tel: +44 (0)151 7943545w Electronic supplementary information (ESI) available: Experimentaldetails, additional data on porous structures and nanoparticles,curcumin light degradation. See DOI: 10.1039/c1cc13509k

ChemComm Dynamic Article Links

www.rsc.org/chemcomm COMMUNICATION

Dow

nloa

ded

by P

enns

ylva

nia

Stat

e U

nive

rsity

on

13/0

5/20

13 1

8:36

:58.

Pu

blis

hed

on 1

0 A

ugus

t 201

1 on

http

://pu

bs.r

sc.o

rg |

doi:1

0.10

39/C

1CC

1350

9KView Article Online / Journal Homepage / Table of Contents for this issue

10002 Chem. Commun., 2011, 47, 10001–10003 This journal is c The Royal Society of Chemistry 2011

Scheme 1 illustrates how a nanocomposite and a nanoparticle

dispersion can be produced. Aqueous polymer solutions and

O/W emulsions were frozen and freeze dried to produce the

required porous materials (see details in ESIw).15,16 Poly (vinyl

alcohol) (PVA) was used as the model polymer because of its

wide applications and its ability to stabilize particles in water.

But in principle any water-soluble polymer can be used to

prepare the porous scaffolds. Cyclohexane (CH) is a nonpolar

volatile organic solvent with a high melting point (B6 1C) and

higher residual requirement for pharmaceutical applications.17

It was used as the internal phase to form O/W emulsions. Four

samples of porous materials with different compositions and

porosities were prepared (Table 1). They showed aligned and

emulsion-templated pore structures (Fig. S1, ESIw).A red dye Oil Red (OR) was selected as the model organic

compound to demonstrate the concept. OR is poorly soluble

in water and floats on the surface as powders when mixed with

water. However, the successful preparation of OR nanoparticles

and subsequent dispersion in water could produce a clear red

‘solution’.14 In this study, the preformed porous materials were

soaked in OR solutions in acetone (ACE) and cyclohexane

(CH). The absorption of organic solutions into the porous

materials was assessed by the ratio of mass gain to the dry

porous materials (Fig. S2, ESIw). For the OR–ACE solution,

S4 showed the maximum mass gain ratio of around 1500%,

which was attributed to its highly interconnected pore structure

and large pore volume.16 Smaller mass gain ratios around

600% were obtained for other samples (Fig. S2A, ESIw). Thissuggested that absorption capacity of porous materials could

be tuned by the porosity of the scaffolds.

Many organic compounds can be dissolved in acetone. But

it is unlikely to form O/W emulsions with acetone solutions.

The OR–ACE solutions were firstly investigated for the

production of organic nanoparticles by solvent evaporation.

Samples S1–S4 were soaked in 0.05 w/v% OR–ACE to reach

absorption saturation and then filtered and allowed to dry in a

fume cupboard at room temperature. Red dry composite

materials were obtained after 1 hour (Fig. 1A). Shrinkage

was observed for all the samples but more significantly for

emulsion-templated porous PVA (S3 and S4). These composite

materials could be dissolved into water rapidly to produce clear

red solutions (Fig. 1B). This indicated that OR nanoparticles

were formed within the porous materials and could be easily

released by dissolution in water. Precipitates were observed in

some dispersions, which was attributed to the formation of

large OR nanoparticles during the evaporation. These large

particles were formed due to the material shrinkage during the

drying process and on the external surface of the porous scaffold.

It was noticed that the evaporation rate could influence

the shrinkage significantly. When the evaporation was fast,

the shrinkage of the materials was significantly reduced. The

soaked materials were thus dried under vacuum to accelerate

the solvent evaporation. In this case, the shrinkage of the

materials was minimal (Fig. 1C). Clear nanodispersions were

formed by dissolving in water without precipitates (Fig. 1D).

The average sizes of the OR nanoparticles are listed in Table 1.

As an example, Fig. 1E and F show a scanning transmission

electron microscopy (STEM) image of organic nanoparticles

and the relevant particles size distribution by dynamic light

scattering (DLS). The average zeta potentials of the OR

nanoparticles from samples S1–S4 were �4.06, �28.3, �31.8and �33.5 mV. As can be seen in Fig. 1B and D, the colour

of the dispersions becomes more intense from left to right.

This suggests that the concentration of OR nanoparticles

increased from samples S1 to S4. There are two reasons for

this phenomenon: (1) the presence of SDS can help disperse

Table 1 Preparation conditions of porous materials and characterization results of aqueous nanoparticle dispersions

PVA/g ml�1 SDS/g ml�1 CHa v/v

OR/nm, FC OR/nm, VOCurcumin/nm

ACE sol CH sol ACE sol CH sol

S1 0.05 0 0 46.0 40.0 40.0 57.0 33.0S2 0.05 0.05 0 37.0 33.0 49.0 55.0 42.0S3 0.05 0.05 1 : 1 41.0 33.0 42.0 48.0 40.0S4 0.05 0.05 1 : 3 46.0 40.0 51.0 64.0 47.0

a CH was emulsified into the aqueous solutions to form emulsions. The ratios are the volume ratios of the aqueous phase to CH. The soaked

materials were either dried in a fume cupboard (FC) or in a vacuum oven (VO) at room temperature.

Fig. 1 Photos of nanocomposite materials by solvent evaporation

with OR–ACE solutions in a fume cupboard (A) and under vacuum

(C). (B) and (D) are the corresponding photos of OR nanodispersions

by dissolving 6.5 mg composites in 1 ml of water (from left to right,

samples S1–S4). (E) STEM image of OR nanoparticles obtained from

S4 in (C). Scale bar: 200 nm. (F) DLS plot for the sample shown in (E).

Dow

nloa

ded

by P

enns

ylva

nia

Stat

e U

nive

rsity

on

13/0

5/20

13 1

8:36

:58.

Pu

blis

hed

on 1

0 A

ugus

t 201

1 on

http

://pu

bs.r

sc.o

rg |

doi:1

0.10

39/C

1CC

1350

9K

View Article Online

This journal is c The Royal Society of Chemistry 2011 Chem. Commun., 2011, 47, 10001–10003 10003

and stabilize OR nanoparticles in water; (2) with the increasing

porosity of S2–S4, an increasing amount of OR solution was

absorbed and hence an increasing number of nanoparticles

formed in the same mass of porous materials.

The effect of the OR concentrations on the size of OR

nanoparticles was further investigated. Sample S4 was used

due to its high absorption capacity. With the increase of OR

concentration, the colour of the red composite was enhanced

(Fig. S3A, ESIw) indicating that the loading of OR nanoparticles

was increased. Except that some aggregates were observed in

the dispersion made from 0.15 w/v% OR–ACE, clear red

nanoparticle dispersions were generated for all these samples

(Fig. S3B, ESIw). The DLS measurements showed that the

average nanoparticle sizes increased from 34, 44, 48 to 60 nm

with the increasing OR–ACE concentrations (Fig. S4, ESIw).It is therefore possible to adjust the sizes of OR nanoparticles

by changing the OR concentrations.

It would be interesting to see how the nanoparticles

prepared by solvent evaporation were compared to those

prepared by freeze drying. Red dry materials were produced

from 0.03 w/v% OR–CH solutions. The red colour seemed

evenly distributed across the materials indicating the formation

of OR nanoparticles uniformly within the materials (Fig. S5B,

ESIw). The average diameters of the OR nanoparticles by DLS

(Table 1) were smaller than the OR nanoparticles (90 nm)

prepared by emulsion freeze-drying even when a higher

concentration of OR solution was used in the evaporation

approach.

This method was further demonstrated with a poorly

water-soluble drug curcumin, which exhibits antioxidant and

anti-tumour properties with potential applications in cancer

therapy.18 The materials were soaked in 0.43 w/v% curcumin–

ACE for 30 min and then dried under vacuum. Yellow

composites with little shrinkage were produced. Clear yellow

nanoparticle dispersions were formed when the composite

materials were dissolved in water (Fig. 2A). The average

diameters were below 50 nm (Table 1). The particle sizes by

STEM (Fig. 2B) were consistent with the DLS measurement.

It is known that curcumin exhibits poor light stability and can

degrade rapidly in solutions in daylight. It was observed

that the curcumin nanodispersions showed better light

stability than curcumin solutions in water/acetone with PVA

and SDS and significantly better than the curcumin solutions

in water/acetone (Fig. S6, ESIw). When required for some

applications, the polymer may be removed from the suspensions

by centrifuging or dialysis with semi-permeable membranes.

In this solvent evaporation approach, there are four major

types of interactions involved: molecule–molecule, molecule–

solvent, molecule–scaffold, and solvent–scaffold.13 The overall

delicate balance of the interactions is required for the production

of organic nanoparticles with controllable sizes. The evaporation

of organic solution on a flat substrate has been employed to

fabricate molecular self-assembly patterns. It was found that

the deposition parameters such as the nature of solvent,

evaporation rate, evaporation temperature were highly

important for the control of self-assembled structures.19 The

dewetting process during solvent evaporation is directly

related to the formation of the nanostructures. It may be

possible by finely adjusting the deposition parameters to

form shape-controlled organic nanostructures in the three-

dimensional porous scaffolds.

In summary, we reported a simple and general approach for

the preparation of organic nanoparticles by solvent evaporation

within water-soluble porous materials. The nanoparticles could

be easily released by dissolution to form aqueous nanoparticle

dispersions. This method provides a potentially useful route to

enhance the solubility of poorly water-soluble drugs by

making drug nanoparticles.20 The efficiency and simplicity of

this method make it easier to be scaled up for large quantity

synthesis and applications.

Notes and references

1 Y. Zhao, H. Fu, A. Peng, Y. Ma, D. Xiao and J. Yao, Adv. Mater.,2008, 20, 2859.

2 A. T. M. Serajuddin, Adv. Drug Delivery Rev., 2007, 59, 603.3 F. Kesisoglou, S. Panmai and Y. Wu, Adv. Drug Delivery Rev.,2007, 59, 631.

4 L. Kang, Z. Wang, Z. Cao, Y. Ma, H. Fu and J. Yao, J. Am.Chem. Soc., 2007, 129, 7305.

5 D. Horn and J. Rieger, Angew. Chem., Int. Ed., 2001, 40, 4330.6 K. Yuyama, T. Sugiyama, T. Asahi, S. Ryo, I. Oh andH. Masuhara, Appl. Phys. A: Mater. Sci. Process., 2010, 101, 591.

7 J. P. Rolland, B. W. Maynor, L. E. Euliss, A. E. Exner,G. M. Denison and J. M. DeSimone, J. Am. Chem. Soc., 2005,127, 10096.

8 H. Murakami, M. Kobayashi, H. Takeuchi and Y. Kawashima,Powder Technol., 2000, 107, 137.

9 M. Li, O. Rouaud and D. Poncelet, Int. J. Pharm., 2008, 363, 26.10 S. Kostler, A. Rudorfer, A. Haase, V. Satzinger, G. Jakopic and

V. Ribitsch, Adv. Mater., 2009, 21, 2505.11 P. Guo, C. R. Martin, Y. Zhao, J. Ge and R. N. Zare, Nano Lett.,

2010, 10, 2202.12 J. A. A. W. Elemans, R. van Hameren, R. J. M. Nolte and

A. E. Rowan, Adv. Mater., 2006, 18, 1251.13 F. J. M. Hoeben, P. Jonkheijm, E. W. Meijer and A. P. H.

J. Schenning, Chem. Rev., 2005, 105, 1491; V. Palermo andP. Samorı, Angew. Chem., Int. Ed., 2007, 46, 4428.

14 H. Zhang, D. Wang, R. Butler, N. L. Campbell, J. Long, B. Tan,D. J. Duncalf, A. J. Foster, A. Hopkinson, D. Taylor, D. Angus,A. I. Cooper and S. P. Rannard, Nat. Nanotechnol., 2008, 3, 506.

15 H. Zhang, I. Hussain, M. Brust, M. F. Butler, S. P. Rannard andA. I. Cooper, Nat. Mater., 2005, 4, 787.

16 L. Qian, A. Ahmed, A. Foster, S. P. Rannard, A. I. Cooper andH. Zhang, J. Mater. Chem., 2009, 19, 5212.

17 A. M. Dwivedi, Pharm. Technol, 2002, (Nov.), 42.18 S. Bisht, G. Feldmann, S. Soni, R. Ravi, C. Karikar, A. Maitra

and A. Maitra, J. Nanobiotechnol., 2007, 5, 3.19 V. Palermo, S. Morelli, C. Simpson, K. Mullen and P. Samorı,

J. Mater. Chem., 2006, 16, 266.20 J. Hu, K. P. Johnston and R. O. Williams, Int. J. Pharm., 2004,

271, 145.

Fig. 2 (A) Photos of aqueous curcumin nanodispersions (from left to

right S1–S4). 2.0 mg composite samples were dissolved into 1 ml of

water to prepare the dispersions. (B) STEM image of curcumin

nanoparticles from sample S4. Scale bar: 200 nm.

Dow

nloa

ded

by P

enns

ylva

nia

Stat

e U

nive

rsity

on

13/0

5/20

13 1

8:36

:58.

Pu

blis

hed

on 1

0 A

ugus

t 201

1 on

http

://pu

bs.r

sc.o

rg |

doi:1

0.10

39/C

1CC

1350

9K

View Article Online