polyester nanoparticles by non-aqueous emulsion polycondensation

Polyester Nanoparticles by Non-AqueousEmulsion Polycondensation

KEVIN MULLER, MARKUS KLAPPER, KLAUS MULLEN

Max Planck Institute for Polymer Research, Ackermannweg 10, D-55128 Mainz, Germany

Received 14 August 2006; accepted 9 November 2006DOI: 10.1002/pola.21874Published online in Wiley InterScience (www.interscience.wiley.com).

ABSTRACT: A versatile non-aqueous emulsion polycondensation process for the mildfabrication of polyester nanoparticles is presented. Spherical nanoparticles withdiameters smaller than 60 nm are prepared in non-aqueous emulsion systems. Theseemulsions consisted in one case of DMF dispersed in n-hexane and in a second withacetonitrile dispersed in a continuous cyclohexane phase. Stabilization of these sys-tems was achieved by using a polyisoprene-polymethylmethacrylate block copolymer.The suitability of these aprotic emulsions for synthesizing polyester nanoparticles byemulsion polycondensation having molecular weights up to 22,000 g/mol is demon-strated. VVC 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 1101–1108, 2007

Keywords: emulsion polymerization; nanoparticles; non-aqueous emulsion; polycon-densation; polyesters

INTRODUCTION

The synthesis and application of polymer nano-particles is of high interest since they have beenused as materials in various fields includingpharmaceutics,1,2 cosmetics,3,4 catalysis,5 and aspowder-coatings.6,7 Of special significance arepolyester nanoparticles as they combine biode-gradability and biocompatibility with good me-chanical properties and softening temperaturescompared to low-density polyethylene and poly-styrene.8,9 The shape and the size of the particlesplay a major role, especially for powder-coating,where small and spherical particles are requiredto obtain high fluidity and smooth, respectivelythin coatings.

Polyester nanoparticles with the size andshape of traditional polymer latex particles, forexample polystyrene, cannot be fabricated up tonow, since reaction conditions involve tempera-

tures up to 250 8C and highly reduced pressuresthat hinder the application of well established la-tex preparation methods. However, three ap-proaches towards polyester particles have al-ready been described: The first one involvesdirect emulsion polycondensation of dicarboxylicacids and dioles in water catalyzed by surfac-tants, such as p-dodecylbenzenesulfonic acid orscandium tris(dodecyl sulfate).10,11 Unfortunately,the excess water shifts the reaction-equilibriumagainst polyester formation. Therefore, only ab-solute molecular weights up to 1500 g/mol havebeen reported for the polyester nanoparticleswithmean diameters ranging from 100 to 500 nm.12

The second strategy involved particle formationby spraying polyester melts or polymers fromsupercritical solution.13,14 This technique led tolarge particles (between 0.5 and 2 lm) with nonperfect spherical shapes. The third approach isbased on dispersion polymerization of polyester-oligomers at temperatures up to 200 8C.15 In thismulti step process synthesis of the oligomers inbulk is followed by emulsification in silicon oiland then polycondensation of the oligomers athigh temperatures.

Correspondence to: M. Klapper (E-mail: [email protected]) orK.Mullen (E-mail:[email protected])

Journal of Polymer Science: Part A: Polymer Chemistry, Vol. 45, 1101–1108 (2007)VVC 2006 Wiley Periodicals, Inc.

1101

To circumvent these severe drawbacks, amethod for the preparation of polyester nanopar-ticles under mild conditions is needed. One suchmethod can be the nonequilibrium polyesterifica-tion between acid dichlorides and dioles.16 How-ever, the use of acid dichlorides as monomersrequires the absence of water during the emul-sion polymerization to obtain high molecularweights.17 Thus, the nanoparticle formation viapolyesterification has to be performed in non-aqueous emulsions. Recently, we reported thepreparation of conjugated polymer nanoparticlesin a nonaqueous emulsion of acetonitrile in cyclo-hexane using polyisoprene-block-polymethylme-thacrylate (PI-b-PMMA) copolymers as stabil-izers.18 In this article, this nonaqueous process ofparticle formation will be extended to polycon-densation reactions that allow the formation ofspherical polyester nanoparticles with high mo-lecular weights at moderate temperatures.

EXPERIMENTAL

Reagents and Solvents

Adipoyl dichloride (ADCl) 98% purity, malonyldichloride (MDCl) 99% purity, 1,4-bis(hydroxy-methyl)cyclohexane (BHC) 99% purity, tereph-thaloyl dichloride (TDCl) 98% purity, and anhy-drous ethylene glycol (EG) 99% purity were pur-chased from Sigma-Aldrich and used as received.Cyclohexane, n-hexane, acetonitrile, N,N0-dime-thylformamide (DMF), extra pure triethylamine(TEA), and pyridine were obtained from ACROSOrganics, and dried over molecular sieves (4 A).Polyisoprene-block-polymethylmethacrylate (PI-b-PMMA) copolymer was prepared using a se-quential anionic polymerization technique de-scribed elsewhere.19,20

Preparation of Polyester Nanoparticles

PI-b-PMMA copolymer (0.450 g) was stirred mag-netically in cyclohexane (24.0 g, 285 mmol) atroom temperature. BHC (0.87 g, 6.0 mmol) wasdissolved in acetonitrile (3.0 g, 73 mmol) andadded dropwise to the cyclohexane/copolymer so-lution. The emulsion was formed by stirring themixture for 2 h, adding dry pyridine (1.21 g, 12.0mmol), and sonication of the solution for 10 min.Subsequently, ADCl (1.21 g, 6.60 mmol) wasadded dropwise (�4.8 mL/h) to the emulsion. Thepolyesterification reaction proceeded while stir-

ring for 2 h. The reaction product was placed in aseparating funnel and an excess of acetonitrilewas added to remove residual emulsifier and gen-erated hydrochloride. The precipitated particleswere separated, washed twice with acetonitrile togive 1 g of a white solid that was dried in vacuumover night or directly redispersed in n-hexane.

Characterization Methods

Gel permeation chromatography (GPC) versuspoly(styrene) standard was carried out at 30 8Cusing MZ-Gel SDplus 10E6, 10E4, and 500 col-umns, an ERC RI-101 differential refractometerdetector, and THF as eluent. Prior to chromato-graphy, samples were filtered through a 0.2 lmTeflon filter (Millipore) to remove insolubleimpurities.

Matrix assisted laser desorption ionization–time of flight (MALDI–TOF) mass spectrometry(MS) spectra were recorded in linear mode usinga Bruker Reflex I mass spectrometer equippedwith a nitrogen laser emitting at 337 nm andworking in positive ion mode with an accelerat-ing voltage of 26.5 kV. 2-(4-Hydroxyphenilazo)-benzoic acid (0.1 M in THF) was used as matrix.For sample preparation 20 lL matrix solutionand 2 lL polyester solution (1 mg/mL in THF)were mixed, 1 lL of each sample/matrix mixturewas spotted on a MALDI sample holder andslowly dried to allow matrix crystallization.

Composition of the PI-b-PMMA copolymer wasdetermined in CDCl3 as solvent by

1H NMR spec-troscopy using a Bruker Avance Spectrometeroperating at 500 MHz.

SEM images were taken by a Zeiss Gemini 912microscope. For SEM sample preparation, thedispersed nanoparticles were drop casted onsilica wafers.

Emulsions were characterized by means ofdynamic light scattering (DLS) at low concentra-tions using a Malvern Zetasizer 3000 with a fixedscattering angle of 908. All other DLS measure-ments were performed at low concentrations onan ALV 5000-correlator using a He/Ne-Laseroperating at 632.8 nm.

RESULTS AND DISCUSSIONS

To obtain stable emulsions suitable for the syn-thesis of polyester nanoparticles, two differentnon-aqueous emulsion systems were investi-gated. The first consisted of acetonitrile dispersed

1102 MULLER, KLAPPER, AND MULLEN

Journal of Polymer Science: Part A: Polymer ChemistryDOI 10.1002/pola

in cyclohexane. The second system was composedof DMF as the dispersed phase in an n-hexanephase. For stabilization of the emulsions, a PI-b-PMMA copolymer having a number average mo-lecular weight of 30,500 g/mol (dispersity 1.1)and a block composition of 69% PI and 31%PMMAwas used (DPPI ¼ 270, DPPMMA ¼ 121). Inboth systems the PI-block, which is only solublein the nonpolar continuous phase, acts as the sta-bilizing moiety and the PMMA-block as theanchor moiety for the dispersed polar organicdroplets.

To study the size of the dispersed droplets, dif-ferent non-aqueous emulsions were prepared byvarying the amount of stabilizer and then charac-terizing the resulting dispersed droplets bymeans of DLS at scattering angles of 608 and 908(Tables 1,2 and Fig. 1).

In the investigated range, the diameter of theacetonitrile droplets in cyclohexane was always

smaller compared to those from DMF droplets inn-hexane. This behavior can be explained byusing the solubility parameters dt of the compo-nents as defined by Hansen.21,22 In general, themiscibility of one component with the otherdecreases if the difference in dt increases. Thus,the varying droplet diameters can be explainedby the higher solubility difference of DMF in n-hexane (Ddt ¼ 10.0 J1/2 cm3/2 mol�1) as comparedto acetonitrile in cyclohexane (Ddt ¼ 7.6 J1/2 cm3/2

mol�1). This property establishes a lower surfaceto volume ratio for the DMF droplets in n-hexaneand therefore leads to bigger droplet diametersin the formed emulsions.

Additionally, it was possible to control the di-ameter of the droplets by varying the concentra-tion of the PI-b-PMMA emulsifier. It appeared forboth systems that the diameter of the dispersed,polar droplets decreased with increasing theemulsifier concentration (Fig. 1). However, a con-

Table 1. Characteristics of Different Non-Aqueous Emulsions, Consistingof 1.5 ml Acetonitrile Dispersed in 15 ml Cyclohexane

EmulsionPI-b-PMMA

(g)

ConcentrationPI-b-PMMA/Continuous

Phase (g/g) (10�2)

Droplet Diameter (nm)

Scattering Angle

608 908

1 0.30 2.54 25.6 22.32 0.26 2.18 24.9 24.53 0.20 1.66 25.4 21.84 0.15 1.24 24.6 23.85 0.10 0.88 23.1 23.86 0.09 0.73 34.7 33.17 0.06 0.51 47.6 43.88 0.02 0.17 94.0 87.0

Table 2. Characteristics of Different Non-Aqueous Emulsions, Consistingof 1.5 ml DMF Dispersed in 15 ml n-Hexane

EmulsionPI-b-PMMA

(g)

ConcentrationPI-b-PMMA/Continuous

Phase (g/g) (10�2)

Droplet Diameter (nm)

Scattering Angle

608 908

1 0.40 3.97 40.5 39.82 0.29 2.87 44.0 41.13 0.21 2.11 65.0 56.04 0.15 1.49 93.0 79.15 0.10 0.99 99.0 98.06 0.05 0.53 Phase separation

POLYESTER NANOPARTICLES BY EMULSION POLYCONDENSATION 1103


stant droplet diameter was observed for each sys-tem after reaching a certain emulsifier concen-tration. As in traditional miniemulsion systems,this behavior can be explained by the fact that atthis steady state the droplets coexist with freemicelles and any increase in surfactant concen-tration does not more influence the diameter ofthe dispersed droplets.23

Polycondensation reactions were performed innon-aqueous emulsions of acetonitrile in cyclo-

hexane and DMF in n-hexane, using pyridine orTEA as base (Table 3). As dioles, BHC 2 and EG4 were chosen. ADCl 1, TDCl 3, and MDCl 5were used as acid dichlorides. With the exceptionof MDCl, polymer nanoparticles were obtained inall cases (Scheme 1). When MDCl and the terti-ary amine were mixed, an exothermic reactionled to black, tarry compounds, which is similar topolycondensation reactions performed in solu-tion.24

To obtain polyester nanoparticles, the diolewas dissolved in the polar organic solvent (aceto-nitrile or DMF) and emulsified in the nonpolarorganic phase. Polymerization was started uponaddition of the dichloride component. During thepolymerization, TEA precipitated as a quater-nary ammonium salt while the pyridine-hydro-chloride remained soluble in the continuousphase. Hence, the hydrochloride, which was re-leased during the polycondensation reaction,could no longer participate in the reverse reac-tion. After polymerization, the nanoparticles wereisolated by precipitation upon addition of excesspolar phase.

As the diole is only soluble in the polar phase,one can safely assume that the polycondensationreaction only occurs in the dispersed phase sinceonly there both monomers are present (Fig. 2),this indicates a miniemulsion mechanism. Un-fortunately, as the acid dichloride monomer dif-fuses into the dispersed, diole-filled droplets dur-

Figure 1. Droplet diameter of different non-aqueousemulsions, measured by DLS at 908 scattering angle,as a function of PI-b-PMMA concentration.

Table 3. Polyesterification Reactions Performed in Non-aqueous Emulsions

Exp. Dichloridendichloride

(mmol) Diolendiole

(mmol) Basenbase

(mmol)Diametera

(nm)Mw

b

(g mol-1) Dc

A1d ADCl 6.6 BHC 6 Pyridine 8 60 22,000 1.7A2d ADCl 6.6 BHC 6 Pyridine 8 60 20,000 2.2A3d ADCl 6.6 BHC 6 Pyridine 13 58 16,000 2.7A4 ADCl 2.5 BHC 2.5 Pyridine 7 43 5000 2.8A5 ADCl 6 BHC 6 TEA 13 38 3200 1.7A6 TDCl 2.5 EG 2.5 TEA 6 60 –e –e

A7d MDCl 6.6 BHC 6 TEA 8 –f –f –f

B8d ADCl 6.6 BHC 6 Pyridine 8 38 3100 1.8B9d ADCl 6.6 BHC 6 TEA 8 38 3200 1.9B10 MDCl 6 BHC 6 TEA 8 –f –f –f

Experimental conditions and results, the dispersed phases were 3 g CH3CN in A and 3 g DMF in B experiments, the continu-ous phases were 24 g cyclohexane in A and 24 g n-hexane in B experiments. Stabilization was achieved by using 0.45 g PI-b-PMMA emulsifier.

a Determined by dynamic light scattering, particles redispersed in hexane at low concentration.b Determined by GPC in THF versus polystyrene standards.c Dispersity of the polymer, determined by GPC.d Acid dichloride component was added slowly in 10% excess using a syringe pump.e Polymers insoluble in THF.f No polymerization.



ing polymerization, the process can be as welldescribed as an emulsion polymerization. Thus,the mechanism cannot be unambiguouslyassigned to either an emulsion or a miniemul-sion process.18

Non-aqueous emulsion polycondensations ledto polyester particles having mean diameterssmaller than 60 nm. The weight average molecu-lar weight of the polymers, determined by GPCversus polystyrene standards, was as high as22,000 g/mol. For this case the yield was nearlyquantitative and the degree of polymerization(DP) was calculated to be 51, corresponding to ahigh monomer conversion of 0.98. The use of ace-tonitrile instead of DMF as the dispersed phaseled to higher molecular weights. This might beexplained by the fact that acetonitrile is a better

solvent for the polyesters and polymerizationcould proceed longer in solution before the poly-ester precipitated within the dispersed droplets.Additionally, DMF can undergo hydrolytic degra-dation forming formic acid, which might termi-nate the polycondensation reaction.25

To obtain high molecular weight polyesters, thedichloride component was added dropwise in a10% excess to the emulsion using a syringe pump(Table 3, Exp. A1–A3, A7–B9). Continuous addi-tion of the acid dichloride ensured a complete con-sumption of the acid dichloride before new mono-mer was added. Thus, the stoichiometry was con-trolled more easily than in the case where thedichloride component was added all at once.Therefore the polycondensation could proceedunder almost optimum conditions. By this slow

Figure 2. Preparation of polyester nanoparticles in a non-aqueous emulsion system.

Scheme 1. Polycondensation reactions carried out in non-aqueous emulsions.



addition method, polyesters with three timeshigher molecular weight than polyesters preparedby complete monomer addition were obtained.

Successful polymerizations were confirmed byMALDI–TOF MS, which showed in all cases therepeating units of the polyesters. For polymeranalysis, the molecular weight distributions werecalculated on the basis of the recorded mass spec-tra (Table 4).

For the investigated polyesters, absoluteweight averaged molecular masses up to 9200 g/mol (Mn 7600 g/mol, dispersity 1.2) were calcu-lated. It can be observed that the molecularweights and dispersities derived from the massspectra are smaller as compared to those ob-tained by GPC. This can be explained by the de-

sorption mechanism within the MALDI–TOFexperiments. Lighter molecules are preferen-tially desorbed and ionized in the MALDI pro-cess, suppressing desorption and ionization oflarger polymer chains.26 Thus, suppressed de-sorption of larger polymer chains led to adecrease in the observed dispersity index.27,28

However, compared to the absolute molecularmasses of different polyesters synthesized inaqueous miniemulsion by Landfester et al.12 theobserved absolute molecular weights by MALDI–TOF MS were up to eight times higher. This mo-lecular weight increase can be explained by theabsence of water during the polymerization incontrast to the water based miniemulsion pro-cess.

NMR characterization of the obtained nanopar-ticles demonstrated that, the particles still have acoating of the PI-b-PMMA emulsifier. Addition-ally, NMR experiments permitted to derive theratio of emulsifier to polyester by comparing thePI-signal of the emulsifier to the CH2��O�� signalof the polyester. For experiment A2 (Table 3) theweight ratio of PI-b-PMMA to polyester wasfound to be 1 to 3.35, this value is similar to theexpected value of 1 to 3.12, derived from originalpolymerization conditions. The higher polyester

Table 4. Molecular Masses of the PolyestersDetermined by MALDI–TOF Mass Spectrometryfor the High Molecular Weight Polyesters

Polymer Mw (g mol�1) Mn (g mol�1) D

A1 9200 7600 1.2A2 8900 6900 1.3A3 6900 5300 1.3

Figure 3. (a) SEM microphotograph and (b) particle size distribution of polyesternanoparticles (exp. A4), mean particle size 38 nm (std. dev. 67 nm) determined bySEM (based on 100 particles).



to emulsifier ratio can be explained throughslight removal of emulsifier during the washingprocedure of the nanoparticles.

Because of their residual emulsifier shell, theparticles could be redispersed in n-hexane afterpurification. The obtained dispersions showed along-term stability (>4 weeks) and were charac-terized by DLS to determine the mean particlediameters (Table 3).

To exclude influences of the PI-b-PMMA co-polymer on the particle size measurements, theparticle size was additionally verified by scan-ning electron microscopy (SEM). A dispersion ofparticles in n-hexane was drop casted onto a sil-icon wafer and the mean particle size wasdirectly calculated from the SEM images basedon 100 particles. A typical SEM image and theparticle size distribution are shown in Figure 3.The mostly separated particles showed a spheri-cal shape and narrow particle size distribution.The SEM-based number average diameter wasfound to be 38 nm (67 nm) whereas the DLS-based number average diameter was found to be43 nm (610 nm). This shows that the particlesare well-dispersed in the n-hexane solution andthat influences exerted by the stabilizer can beneglected.

CONCLUSIONS

Two versatile non-aqueous emulsion systems,stabilized by a PI-b-PMMA copolymer, are pre-sented and the fabrication of polyester nanopar-ticles is described. Spherical polyester latex par-ticles with average diameters smaller than60 nm were obtained by nonequilibrium emulsionpolycondensation under mild conditions. In con-trast to the methods described in the literature,this process allows the fabrication of sphericalparticles with sizes below 60 nm within one step.The molecular weight of the polyesters werefound to be up to 22,000 g/mol, which was morethan 12 times higher compared to the surfactantcatalyzed direct emulsion condensation methodof dicarboxylic acids and dioles. In brief, this isthe first method that synthesizes spherical, highmolecular weight polyester nanoparticles in onestep at ambient temperatures.

It is expected that these polyester nanopar-ticles will find applications as powder-coating,biocompatible binding agents in cosmetics orpharmaceutics, or as toner particles in electro-photography.

Based on our previous studies,18 which in-cluded catalytic and oxidative polymerizations innon-aqueous emulsions, the broad applicability ofnon-aqueous emulsions for the synthesis of poly-mer nanoparticles is demonstrated. One antici-pates, that non-aqueous emulsions will offer ver-satile access towards novel polymer nanopar-ticles. Currently, further directions of this workinvolve the influence of emulsion composition onthe size of the nanoparticles and the fabricationof polyurethane and core/shell nanoparticles.

The authors acknowledge Thomas Wagner and Jur-gen Thiel for the synthesis of the PI-b-PMMA copoly-mers, Anna Cristadoro for MALDI-TOF MS measure-ments, and BAYER AG for financial support.

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polyester nanoparticles by non-aqueous emulsion polycondensation

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