Materials Science and Engineering C 29 (2009) 514–518

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Materials Science and Engineering C

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Polymeric nanocapsules via miniemulsion polymerization using redox initiation

Ana Paula Romio a, Neusa Bernardy a, Elenara Lemos Senna b, Pedro H.H. Araújo a, Claudia Sayer a,⁎a Department of Chemical Engineering and Food Engineering, Federal University of Santa Catarina, 88040 900, Florianópolis, Brazilb Department of Pharmaceutical Sciences, Federal University of Santa Catarina, Florianopolis, Brazil

⁎ Corresponding author. Tel.: +55 48 3721 9448 243;E-mail address: csayer@enq.ufsc.br (C. Sayer).

0928-4931/$ – see front matter © 2008 Elsevier B.V. Aldoi:10.1016/j.msec.2008.09.011

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Article history:

The effect of using a redox in Received 5 May 2008Received in revised form 5 September 2008Accepted 6 September 2008Available online 15 September 2008

Keywords:Miniemulsion polymerizationPolymeric nanocapsulesMethyl methacrylateRedox initiation

itiation system (hydrogen peroxide and ascorbic acid), on the morphology of thenanoparticles formed in methyl methacrylate miniemulsion polymerization reactions with lecithin assurfactant and using high amounts of miglyol 812 or castor oil as costabilizer is compared to the use of aconventional organic phase initiator (2,2′-azo-bis-isobutironitrile). It was observed that with miglyol 812 asco-stabilizer the preferential formation of the nanocapsule morphology was achieved with both evaluatedinitiation systems when initiator concentrations were chosen in such a way that monomer conversions of90% were only attained after 30 min of reaction.

© 2008 Elsevier B.V. All rights reserved.

1. Introduction

The control of the morphology of polymeric nanoparticles is anarea of great importance of Polymer Science and Technology [1–4].The term nanoparticles is a common name for nanospheres andnanocapsules. Nanospheres have a matricial structure and nanocap-sules, in turn, are vesicular systems inside of which active componentsmay be confined in a cavity which consists of a liquid nucleus (an oilwhich may dissolve lipophilic agents) and surrounded by polymershell in the order of nanometers [5,6]. Several different techniquesmay be used to produce these nanocapsules as osmotic swelling [7],encapsulation of a non-solvent [8], water-in-oil-in-water emulsion[9], swelling with a solvent [10], incorporation of an expansion agent[11] and miniemulsion polymerization [1]. The synthesis of nanocap-sules via miniemulsion polymerization shows as advantage, inrelation to the other methods, the possibility of obtaining nanocap-sules in one single reaction step and is based on the differences of theinterfacial tension and on the phase separation process duringpolymerization [1].

In miniemulsion polymerizations, the monomer is previouslydispersed in 50–500 nm droplets by shear forces (stator–rotorsystems, sonifiers or high pressure homogenizers), and these dropletsare stabilized by the combination of a surfactant and a co-stabilizer,that is highly insoluble in water. The co-stabilizer is used to retard thediffusional degradation (Ostwald ripening) and the surfactant is usedto minimize the coalescence of the droplets. As these monomerdroplets are sufficiently small and, consequently, numerous, andmicelles do not exist in a well prepared miniemulsion, monomer

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droplet nucleation becomes the predominant in the miniemulsionpolymerization, turning possible, consequently, the encapsulation ofdifferent types of inorganic particles in the polymer particles.

Since droplet nucleation is the predominant particle nucleationmechanism in miniemulsion polymerizations and due to the smalldroplet sizes, these reactions might be conducted either with organicphase initiators dissolved in the monomer phase, or with aqueousphase initiators. In the former case the miniemulsion polymerizationproceeds in a similar way to the suspension polymerizations, but in asubmicrometric scale with the characteristic features, as for instance,radical recombination inside submicrometric monomer dropletswhich led to the development of the “single radical theory” [12]. Inthe latter case, radical formation occurs in a similar way to theconventional emulsion polymerizations and, consequently, dependingon the formulation and reaction conditions, additional particlenucleation mechanisms as micelar and or homogenous nucleationmechanisms might not be excluded. Saethre et al. [13] observed thatparticle nucleation by other mechanisms besides droplet nucleationincreased with the solubility of the initiator in the aqueous phase andthat reactions with hydrogen peroxide resulted in less homogeneousnucleation than potassium persulfate, probably due to the surfaceactivity of the sulfate terminated radicals that may provide some self-stabilization to particles nucleated by the precipitation of theoligoradicals.

Tiarks et al. [1] verified the effect of different initiators, 2,2′azobisisobutyronitrile (AIBN), azodi(poly(ethylene glycol) isobutyrate(PEGA 200) and potassium persulfate (KPS), on the formation of thenanocapsule morphology during styrene miniemulsion polymeriza-tions with hexadecane as co-stabilizer and sodium lauryl sulphate assurfactant. The authors observed that whereas in the reactions withAIBN or PEGA 200 the nanocapsule morphology was formed, the use

Fig. 1. Chemical structure of surfactant and of co-stabilizers. a) Lecithin (R1 and R2 are linear aliphatic groups with C15–C20 and up to 4 double bonds); b) Miglyol 812; c) Castor oil.

Table 1Formulations of MMA miniemulsion polymerizations

Reactants Reactions

(wt/wt.%) Exp 02⁎, 04, 07 Exp 32⁎, 33 Exp 39 Exp 50⁎, 51, 52

Water 79.6 79.6 79.6 79.6Lecithin 0.298 0.298 0.298 0.298Miglyol 812 9.95 9.95 – –

Castor oil – – 9.95 9.95MMA 9.95 9.95 9.95 9.95AIBN 0.232 – 0.232 –

H2O2 – 0.10 – 0.10AscAc – 0.016 – 0.016

⁎ Experiments in duplicate or triplicate.

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of a standard water-soluble ionic initiator, KPS, did not lead to theformation of nanocapsules, but mostly to the formation of sphericalpolystyrene particles. This work of Tiarks et al. [1], which involves theformation of poly(methyl methacrylate) and polystyrene nanocap-sules using hexadecane as hydrophobe, is one of the few works thathave been published about the formation of polymer nanocapsules viaminiemulsion polymerizations. Rajot et al. [14] and Bathfield et al. [15]encapsulated a biocompatible hydrophobe, miglyol, in polyvinylacetate and in polystyrene particles, using Pluronic 86 and themacromonomer caprolactam as non-ionic biocompatible surfactant.And Crespy et al. [16] synthetized poly(divinylbenzene) nanocapsulesusing AIBN as initiator, hexadecane as hydrophobe and an anonionicpolymerizable surfactant, Tego XP-1008.

The applicability of nanocapsules in the biomedical field can beenhanced when biodegradable and biocompatible materials are used.Lecithin is formed by non-toxic phosfolipids, being biocompatible,biodegradable and coming from renewable sources as soya beans andwas used as surfactant in miniemulsion polymerizations envisagingthe formation of biocompatible polymeric nanocapsules [17–19].Romio et al. [18] studied the formation of stable poly(methylmethacrylate) nanoparticles via miniemulsion polymerization usingNeobee M-5 from a renewable source (coconut oil) as costabilizer andlecithin as biocompatible and biodegradable surfactant, viewingfuture biomedical applications. For this, the effect of differentconcentrations of lecithin and of dispersion energies on themorphological characteristics of the final latex was evaluated.Bernardy et al. [19] carried out a comparative study of methylmethacrylate miniemulsion polymerization reactions for the forma-tion of biocompatible nanocapsules and nanospheres using Miglyol812 as costabilizer and lecithin as surfactant and verified the effects ofthe fraction of the organic phase and of the surfactant concentrationon the kinetics and on average particle size and number during MMAminiemulsion polymerizations.

In this work the effect of using a redox initiator system composedof ascorbic acid and hydrogen peroxide was evaluated for theformation of PMMA (model polymer) nanocapsules via miniemulsionpolymerization using Lecithin as surfactant and Mygliol 812 or castoroil as co-stabilizer. This redox initiation system has the advantage,over commonly used aqueous phase initiators, as potassium persul-fate, sodium persulfate or ammonium persulfate, of not providingsurface charges to the nanoparticles, which besides of being able toenhance the homogeneous particle nucleation (undesired in theminiemulsion polymerizations aiming the formation of nanocap-sules), are prohibited for some biomedical applications. Results werealso compared with those of reactions conducted with conventionaloil soluble initiator 2,2′azobisisobutyronitrile (AIBN).

2. Experimental procedures

2.1. Materials

Methyl methacrylate (MMA) from Arions Química and theinitiators, 2,2′azobisisobutyronitrile (AIBN, 98%) and hydrogen per-

oxide (H2O2) and ascorbic acid (AscAc), from Vetec Química. Lecithinwas purchased from Alfa Aesar. Co-stabilizers, Miglyol 812 from Sasoland castor oil from Viafarma. All materials were used as received.Distilled water was used in all experiments. Fig. 1 shows the chemicalstructure of the surfactant, lecithin, and of the co-stabilizers evaluatedin this work. Miglyol 812 is a triglyceride of saturated fatty acids,predominantly caprylic acid (50 to 65%) and capric acid (30 to 45%),while the castor oil is a triglyceride in which 83.6 to 90% of the fattyacid chains are composed of ricinoleic acid [20], which, in turn, is amonoinsaturated fatty acid that contains a hydroxyl group.

2.2. Miniemulsion polymerizations

Methyl methacrylate miniemulsion polymerizations were carriedout aiming the formation of polymeric nanocapsules. In order to formthe nanocapsules, the co-stabilizer besides of retarding the diffusionaldegradation (Ostwald ripening), is also responsible for the formation ofthe liquid core of the particle. This way, the monomer must be solublein the co-stabilizer and the polymer must be insoluble to allow theformation of the nanocapsule morphology. In addition, the polymermust be more hydrophilic than the co-stabilizer.

The organic phase composed of MMA, Miglyol 812 or castor oil,lecithin and, if used, AIBN, was prepared according to the formulationsshown in Table 1 and magnetically stirred for 10 min. In sequence, theorganic phase was added to the aqueous phase (water) and thedispersion was stirred for 5 min with a magnetic stirrer beforesonication with an ultrasound probe (Fisher Scientific, Sonic Dis-membrator Model 500) during 4 min with an amplitude of 60% toprepare the miniemulsion. The effect of the dispersion time andconditions (amplitude, sample volume, becher volume and dimen-sions as well as presence or absence of magnetic stirring) on theaverage diameter of the initial droplet size distribution and on thereaction kinetics during MMA miniemulsion polymerizations wereevaluated in a previous work [18]. To avoid the early onset ofpolymerization, the miniemulsion was cooled in an ice-bath duringsonication. In the reactions with the aqueous phase initiators, a smallaliquot of water from the formulation was separated for thedissolution of the initiator, which was added to the miniemulsion

Fig. 2. TEM image and PSD of nanocapsules: PMMA/Miglyol 812/Lecithin/AIBN (Exp 04).

516 A.P. Romio et al. / Materials Science and Engineering C 29 (2009) 514–518

right after the sonication. Concentrations of the different initiatorsevaluated in this work were chosen in such a way that monomerconversions of 90% were only attained after 30 min of reaction.

Batch polymerization reactions were carried out in 20 mlampoules immersed in a thermostatic bath at constant temperature(70 °C). Samples were removed periodically and reaction was shortstopped with the addition of a 1 wt.% hydroquinone solution.

2.3. Analyses

Conversion was calculated based on gravimetric data. Averagediameters of monomer droplets (Dg) and of polymer particles weremeasured by dynamic light scattering (DLS – Malvern Instruments,Zeta Sizer Nano S). For these measurements, samples were diluted indistilled water saturated with monomer in order to prevent monomerdiffusion from the droplets to the continuous phase. Particle number(Np) was calculated based on average particle diameter and conver-sion measurements. Final reaction samples were also analyzed bytransmission electron microscopy (TEM – JEOL JEM 2100) for theevaluation of the morphology of the nanocapsules and the determina-tion of their particle size distribution. For this analysis, several drops ofthe diluted sample were placed on a 300 mesh Formvar copper grid.After drying samples were sputter-coated with a thin carbon film to

Fig. 3. TEM image and PSD of nanocapsules: PMMA

avoid the degradation of the PMMA under the electron beam andobserved at 100 kV. The free software Size Meter, developed at theChemical Engineering and Food Engineering Department of theFederal University of Santa Catarina, was used for the determinationof the particle size distribution.

3. Results and discussion

This work aims to verify the effect of different initiator systems, aconventional organic phase initiator (AIBN) and a redox initiationsystem (H2O2 and AscAc), on the morphology of the nanoparticlesformed in methyl methacrylate miniemulsion polymerizations.

Fig. 2 shows the TEM image and the particle size distribution (PSD)of the nanocapsules formed in the methyl methacrylate miniemulsionpolymerization using lecithin as surfactant, miglyol 812 as co-stabilizer and the organic phase initiator, AIBN. It might be observedthat this organic phase initiator, which helps to minimize undesiredaqueous phase nucleation mechanisms, leads to the preferentialformation of the nanocapsule morphologywith a relatively broad PSD.The number average particles size (Dpn) and the volume averageparticle size (Dpv) were calculated with the PSD obtained by TEMwhereas the average intensity particle size diameter (Dp) wasobtained through DLS. These values are given in Fig. 2.

/Miglyol 812/Lecithin/H2O2 and AscA (Exp 32).

Fig. 4. Evolution of properties during MMA miniemulsion polymerizations usingMiglyol 812 as co-stabilizer, lecithin as surfactant and different types of initiator.

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In Fig. 3 it can be noted that, despite the solubility in the aqueousphase, the redox initiation system, H2O2 and AscAc, also leads to thepreferential formation of the nanocapsule morphology. This resultshows the predominance of the droplet nucleation mechanism, sincethe co-stabilizer would not be able to migrate from the originalmonomer droplets to the core of PMMA particles newly nucleated byaqueous phase nucleation mechanisms. It is interesting to observe inthis figure that even very small particles show the nanocapsulemorphology.

Fig. 4 compares the evolutions of conversion, average particlediameter and particle number during the methyl methacrylateminiemulsion polymerizations using lecithin as surfactant, miglyol812 as co-stabilizer and the different types of initiators. In Fig. 4a itmight be observed that in all reactions 90% of monomer conversion

was only achieved after 30 min of reactions. Reactions with theconventional organic phase initiator (AIBN) and with the redoxinitiation system (H2O2 and AscAc) resulted in quite similar averageparticle size and number evolutions, maintaining the initial monomerdroplets number. This result appoints to the absence of undesiredmechanisms of coalescence, diffusional degradation and micellar and/or homogenous particle nucleation.

Fig. 5 shows the TEM image of the nanocapsules formed in themethyl methacrylate miniemulsion polymerization using lecithin assurfactant, castor oil as co-stabilizer and AIBN as initiator. It might beobserved that only a reduced number of particles showed themorphology of nanocapsules. This may probably be attributed to themore hydrophilic character of the castor oil due to the presence of thehydroxyl groups in its molecular structure (Fig. 1).

In Fig. 6 it might be noted that both reactions with castor oilpresented the same number of particles and the same initialpolymerization rate. Although, when the reaction reached 30 min,the polymerization rate of the reaction with H2O2/AscA decreasedsharply. A similar result, at a higher conversion, was observed forthe reaction with H2O2/AscA and Miglyol 812 (Fig. 4), indicatingthat the average number of radicals per polymer particle wasdrastically reduced. Also, reactions with castor oil as co-stabilizerwith both types of initiator (AIBN and H2O2/AscA) showed lowerreactions rates than those with Miglyol 812. In addition, reactionswith castor oil resulted in the formation of slightly biggerparticles and, consequently, in a lower amount of particles. Thissmaller number of particles in the reactions with castor oil mighthelp to explain the lower reaction rates of these reactions.Furthermore, as might be observed in Fig. 1 with the chemicalstructures of the co-stabilizers evaluated in this work, Miglyol 812is a triglyceride of saturated fatty acids, while castor oil is atriglyceride of unsaturated fatty acids. Therefore, in addition tothe chain transfer reactions to the co-stabilizer, in the reactionswith castor oil radicals could also react with the double bonds ofthe ricinoleic acid originating tertiary carbon radicals with lowreactivity.

4. Conclusions

Methyl methacrylate miniemulsion polymerizations usingMiglyol 812 as co-stabilizer led to the preferential formation ofthe morphology of nanocapsules with both of the evaluatedinitiators, the oil soluble initiator AIBN and the redox initiationsystem, H2O2 and ascorbic acid. A future paper will explore furtherthe advantage of the this redox initiation system that allows the useof milder conditions (lower reaction temperatures), which in manycases are required to preserve the active components encapsulatedduring the reaction, besides of increasing working security anddecreasing costs.

In the MMA miniemulsion polymerizations using castor oil as co-stabilizer only few particles were formed with the nanocapsulemorphology, possibly due to the more hydrophilic character of castoroil. In addition, reactions with castor oil presented lower reactionsrates than reactions with Miglyol 812 as co-stabilizer. This might theattributed to the lower particle number observed in the reactions withcastor oil and, eventually, also to the occurrence of reactions with thedouble bonds of the ricinoleic acid of the castor oil originating tertiarycarbon radicals with low reactivity.

Acknowledgement

The authors thank the financial support from CNPq – ConselhoNacional de Desenvolvimento Científico e Tecnológico, Sasol forproviding Miglyol 812 and LCME – Laboratório Central de MicroscopiaEletrônica of the Federal University of Santa Catarina for the TEManalyses.

Fig. 6. Evolution of properties during MMA miniemulsion polymerizations using castoroil as co-stabilizer, lecithin as surfactant and different types of initiator.

Fig. 5. TEM image of nanoparticles: PMMA/Castor oil/Lecithin/AIBN (Exp 39).

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