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Synthesis of spherical core-shell poly(vinyl acetate)/poly(vinyl alcohol) particles for use in vascular embolization: study of morphological and molecular modifications during shell formation.


Polymer materials find widespread use in several fields, including many medical practices, as polymer products can be used as excipient of pharmaceutical formulations, embolic device in transarterial vascular embolization procedures, and as drug delivery systems, among many other applications [1-4]. Transarterial vascular embolization has become a common medical procedure to treat some types of tumor and vascular diseases [5]. The embolization procedure consists of the physical occlusion of a blood vessel, performed by a micro-sized material that is injected near to the desired target region. The physical occlusion leads to an ischemic local effect and the death of local tissue [6, 7]. The chemoembolization technique [8, 9] is a modified embolization procedure, performed when the embolic agent is loaded with a drug. The final effect is a combination of the physical occlusion of the blood vessel and the local chemical action of the drug [ 10]. Although many distinct materials have been used as embolic agents [6, 11-14], polyfvinyl alcohol), commonly known as PVA, still remains as the most used material in embolization and chemoembolization procedures due to its intrinsic biocompatibility [15, 16].

PVA is a water-soluble and biodegradable synthetic polymer used over a century in a several range of different applications [2]. Once that the PVA cannot be synthesized by a direct polymerization process (the vinyl alcohol monomer is not chemically stable), this polymer is normally obtained through the chemical modification of another material, usually polyvinyl acetate) (PVAc). Thus, a common strategy used to obtain PVA is to first synthesize a raw material and then promote a suitable chemical modification reaction, such as an alkaline hydrolysis (saponification) or a transesterification reaction (alcoholysis) [17-19]. Consequently, the characteristics of the obtained PVA are directly related not only to the process variables of the modification reaction, but also to the characteristics of the raw material used. In general, PVA resins produced industrially are obtained by transesterification of PVAc using a suitable alcoholic solution. As PVA resins are insoluble in the alcohol media used to perform the modification reaction, precipitation of PVA takes place in form of irregular flakes when the modification reaction is performed. In order to obtain PVA particles with a defined morphology, alternative strategies must be devised.

Among all desirable properties of an ideal embolic agent [20], which includes its biocompatibility and non-carcinogenicity, three characteristics are particularly important: chemical properties, size and morphology of the material [21]. As mentioned before, PVA is one of the most used material as embolic agent due to its favorable chemical properties to such application [15, 16], which includes not only biocompatibility, but also non-carcinogenic and water-solubility properties, which makes it full compatible to be use in human applications [2]. However, since it is difficult to produce PVA particles with defined morphology and size through conventional transesterification reaction, over the past years, several authors reported the synthesis of partially hydrolyzed PVAc beads, by exploring a synthetic route that comprises the synthesis of PVAc through suspension polymerization and post-modification reactions, to obtain a core-shell like material comprised of a PVAc core and a PVA shell [22-27]. This also includes a sequential two-stages process develop in our research group [21, 28], to produce spherical core-shell PVAc/PVA particles that were successfully used in embolization procedures [21, 29]. We have also investigated the effects of different conditions on the original proposed process, including the use of solvents for reduction of the particle density, of comonomer for increase of the glass transition temperature ([T.sub.g]), and the in situ addition of drugs for potential chemoembolization applications [30-34].

The use of partially hydrolyzed PVAc beads with core-shell structure in embolization procedures leads to many advantages, including the fact that the PVA shell is bonded to a PVAc nucleus that it is insoluble in aqueous solutions. This prevents the particles from dissolving when they are put in contact with aqueous solutions, also leading to improved mechanical and chemical stability of the particles. In addition, particles with a core-shell structure tend to absorb less amounts of water, since the PVA can be made as a thin layer, increasing the dimensional stability of the particles and reducing the chances of catheter obstructions [21, 30]. However, the existence of a PVA shell is fundamental to improve the compatibility of the PVAc/PVA particles with the surrounding tissues.

Although the modification of PVAc in PVA has been extensively studied in the literature [17-19], attention has not been given to the detailed analysis of the hydrolysis step used to produce spherical PVAc/PVA micro-particles with core-shell morphology. Most published studies, apart from not providing a full characterization of the used raw material, usually promote the partial hydrolysis of the PVAc beads based on pre-established modification reactions, where the experimental conditions were apparently defined based on empirical observations [22-27]. For this reason, the aim of the present work is to evaluate the effects of the hydrolysis reaction on the final morphology and molecular properties of the produced PVAc/PVA particles. As shown in the next sections, mild hydrolysis conditions do not affect the overall morphology and the thermal properties of the particles. However, it was found that hydrolysis reaction could lead to modifications of the final particle size distribution as well as the molecular weight properties of the copolymers.



Benzoyl peroxide (BPO, 97%), anhydrous calcium chloride (Ca[Cl.sub.2], 96%), hydroquinone (99%), poly(vinyl alcohol) (PVA, Mw = 78 kg/mol and degree of hydrolysis of 85%), sodium hydroxide (NaOH, 99%), and vinyl acetate (VAc, 99%; stabilized with 17 ppm of hydroquinone) were purchased from Vetee Quimica Fina (Rio de Janeiro, Brazil). Tetrahydrofuran (THF, HPLC grade, 99.9%) was purchase from Tedia Brasil (Rio de Janeiro, Brazil). The water used in all experiments was distilled, demineralized, and micro-filtrated. VAc was purified as described previously [28]. All other chemicals were used as received without further purification, except when explicitly indicated.

Synthesis of PVAc Spherical Particles

PVAc spherical particles were synthesized following the basic methodology described previously [24, 28], with some minor experimental adaptations. Free-radical suspension polymerization reactions were carried out in a 1 L-jacketed glass reactor. Initially, the reactor flask was fed with a solution containing water (0.42 L) and PVA (0.20 g). When the desired reaction temperature had been reached (75[degrees]C), a solution containing BPO (2 g) and purified VAc (200 g) was added into the reactor. The system was kept under isothermal conditions with constant agitation of 700 rpm. During the reaction, the reactor was kept closed with its top lid, which was equipped with a reflux condenser connected to a cold bath at 5[degrees]C. After 240 min of reaction, the reaction temperature was reduced to 30[degrees]C, and the polymer powder was filtrated with cold distilled water and dried at atmospheric pressure at 25[degrees]C.

Design of Experiments

In order to analyze the influence of the NaOH concentration (M), temperature (T) and reaction time (t) on the partial hydrolysis of spherical PVAc micro-particles, a [2.sup.3] factorial design experimental plan was selected (Table 1), composed of eight unique experiments (1-8) and three central experiments (experiments 9-11). The high (+), lower (-), and central (0) levels were selected in order to allow the computation of the interaction of the NaOH concentration (M), temperature (T), and reaction time (t), which can be considered the main important factors in hydrolysis reactions. Responses chosen as important to describe the PVAc/PVA performance as embolic agent were particle size, molecular weight averages ([M.sub.n] and [M.sub.w]), polydispersity index ([M.sub.w]/[M.sub.n]), glass transition temperature ([T.sub.g]), and degree of hydrolysis. Empirical regression analyses were used to analyze the effects of the main factors and its interactions.

Synthesis of PVAc/PVA Spherical Particles

PVAc/PVA particles were synthesized using different reaction conditions according to the experimental plan presented in Table 1. Using the same reaction system described before to produce the PVAc particles (after cleaning and drying of the apparatus), the reactor was initially fed with 0.16 L of water and 0.04 L of a NaOH solution with the specified NaOH concentration, as defined in the experimental plan. When the desired reaction temperature was reached, 40 g of previously prepared PVAc particles was slowly added into the reactor. Then, the system was kept under isothermal conditions with constant agitation of 300 rpm during a determined hydrolysis time. During the reaction, the reactor was kept closed with its top lid and equipped with a reflux condenser connected to a cold bath kept at 5[degrees]C. After reaction, the temperature was reduced to 30[degrees]C, and the polymer powder was filtrated with cold distilled water and dried at atmospheric pressure at 25[degrees]C.


Scanning electron microscopy was used to determine the particle morphology, using a Quanta 200 microscopy (FEI Company, USA). Samples were covered with a thin layer of gold (300 nm) on a JFC-1500 ion-sputtering device (JEOL, Japan) prior to analysis. Particle morphology was also verified with help of an optical microscope SMZ 800 (Nikon, Japan).

Light Scattering was used to determine the particle size distribution using a Mastersizer 2000 (Malvern, UK) and a small amount of dry sample. Before analyses, the samples were submitted to gentle manual milling, in order to disaggregate macroscopic lumps. The overall integrity of polymer particles was verified through optical microscopy.

Molecular weight averages and polydispersities were determined by Size Exclusion Chromatography (SEC). Analyses were performed in THF at 40[degrees]C with flow rates of 1 ml [min.sup.-1] using a Viscotek solvent/sample module VE2001, equipped with four Phenomenex columns ([10.sup.6], [10.sup.5], [10.sup.3], and 500 [Angstrom]) and a Viscotek refractometer VE3580. The system was calibrated with polystyrene standards ranging from 0.5 to 1,000 kg/mol.

Glass transition temperature ([T.sub.g]) was determined by Differential Scanning Calorimetry (DSC) using a DSC-7 equipment (Perkin-Elmer, USA). The equipment was calibrated with zinc and indium standards, with onset temperatures of 419.5[degrees]C and 156.6[degrees]C, respectively. Samples (approximately 15 mg) were weighed in sealed aluminum DSC pans and then loaded into the DSC instrument at room temperature, using an empty pan as a reference. Samples were then cooled at 100[degrees]C/min to -20[degrees]C, held at constant temperature for 3 min and then scanned at 10[degrees]C/min, from -20 to 140[degrees]C. This cycle was performed two times and the second scan was used to determine the [T.sub.g] value. The degree of hydrolysis of the PVAc/PVA samples were estimated using the Fox equation (Eq. 1), where [T.sub.g1,2], [T.sub.g1], and [T.sub.g2] are the glass transition temperatures of the PVAc/PVA copolymer, PVAc (42.3[degrees]C), and PVA (84.8[degrees]C) homopolymers, respectively, and [alpha] is the weight fraction of PVA in the copolymer particles.

1/[T.sub.g1,2] = 1 - [alpha]/[T.sub.g1] + [alpha]/[T.sub.g2]. (1)

Sample crystallinity was determined with help of an X-ray diffractometer (Miniflex/Rigaku), using CuK[alpha] radiation and 30 kV/15 mA beam voltage. Analyses were performed varying the angle 2[theta], from 2[degrees] to 80[degrees], with a step width of 0.05[degrees].


General Considerations

The methodology selected to synthesize the embolization particles was first described in our research group [21, 28] and was designed to be performed as a sequential two-stage process, where first a PVAc core is synthesized by suspension polymerization of VAc and then hydrolyzed in situ to form PVAc/PVA particles with a core-shell morphology. The key aspect of the methodology includes the use of commercial available chemicals, performing of the polymerization reaction in suspension, and the operation of the reactor at atmosphere pressure. These characteristics allow an easier scale-up adaptation of the technique to industrial scales.

However, in order to evaluate the effects of the hydrolysis reaction on the final morphology and molecular properties of the produced PVAc/PVA particles, exceptionally in the present work, the two stages of the process were performed as independent steps. First, all PVAc spherical micro-particles were synthesized and fully characterized. Afterwards, the previously PVAc particles were partially hydrolyzed under mild reaction conditions. All other process conditions were kept as close as possible to the original methodology proposed.

PVAc Particles

It can be difficult to synthesize PVAc spherical particles through suspension free radical polymerization of VAc [21], because of the low [T.sub.g] values, low conversions, and high contents of residual monomer. These are some of the reasons that can promote particle aggregation and loss of the spherical morphology after polymerization of VAc. In order to overcome and minimize these problems, strategies must be used, such as the use of co-monomers and/or achievement of high monomer conversions [31, 34, 35]. In our particular case, in order to avoid major changes in the original methodology, it was chosen to use purified VAc as strategy to achieve high monomer conversion. As expected, once that the purification process removes inhibitor and contaminants of the monomer, it becomes possible to achieve much higher monomer conversions (~95%) when the monomer used is not purified (~83%).

Since free radical polymerization of vinyl monomers can be sensitive to the presence of air and oxygenated compounds, strategies must be considered to achieve high conversions in VAc polymerizations, which include the use of inert atmospheres and/or other initiators, then BPO [36-38]. As example, the use of azo-initiators usually promotes higher reaction rates at low temperature and concentration, besides the fact that no oxygenated compounds are generated during the initiator decomposition. However, we recently showed that, for the VAc polymerization, the presence of air and oxygenated compounds seems to be critical only when chain transfer agents are used to control the final molecular properties of the reaction [35]. Thus, it was possible to use the same previously established conditions (atmosphere pressure, high temperature, and BPO as initiator) and a purified VAc monomer (Fig. 1) to synthesize PVAc micro-particles with key macroscopic properties: white color, high stability at room temperature, well-defined spherical morphology, and no-tendency to form aggregates.

For embolization and chemoembolization procedures, particles must present a well-defined particle size distribution, usually in the range of 300-700 [micro]m [39]. Particles with small size (40 [micro]m) can be used in some transarterial chemoembolization procedures, although inadequate migration to other tissues and undesirable embolization effects can take place [40]. Figure 2 shows the size distribution for PVAc and modified PVAc/PVA spherical particles (as will be discussed later). In general, the conditions used to perform suspension polymerizations of VAc allow for production of particles with adequate size distributions and in the range of interest for use as embolic agents. Narrower size distributions can be obtained if particles are classified after drying through sieving or if the advanced control of the final particle size can be achieved through manipulation of process variables during the suspension polymerization reaction [41].

In relation to the molecular properties, Fig. 3 shows the molecular weight distributions of PVAc samples synthesized using different qualities of VAc monomer. As expected, higher molecular weight averages could be achieved when purified VAc monomer is used. However, despite the distinct molecular weight distributions, the [T.sub.g] of PVAc samples are not very sensitive to the molecular weight distribution, increasing from 41.4[degrees]C to 42.3[degrees]C when monomer is purified.

Based on these results, the use of purified VAc showed to be an interesting approach to produce well-defined PVAc spherical micro-particles using a very robust suspension polymerization technique. However, it is important to emphasize that particles synthesized with a non-purified monomer formed aggregated lumps only after drying. This indicates that it is also possible to obtain stable PVAc particles with a non-purified monomer, if other strategies are used to achieve high molecular weights and conversions.

PVAc/PVA Spherical Particles

As previously discussed, a common strategy to produce PVAc/PVA micro-particles with a core/shell morphology it is to first synthesize a PVAc core and then promote a modification reaction at the particle surface. In theory, depending on the final application of the particles, the modification reaction is conducted to promote the modification of PVAc in PVA until a certain degree (Fig. 4). Once more, it is important to emphasize that, despite the modification of PVAc in PVA has been extensively studied in the literature, attention has not been given to the detailed analysis of the hydrolysis step used to produce spherical PVAc/PVA micro-particles. This also becomes more relevant when synthesizing particles to be used in embolic procedures, where the particle morphology, surface characteristics, and molecular properties play important roles in the final performance of the material.

Using the spherical PVAc previously synthesized, PVAc/PVA core-shell particles were prepared by hydrolyzing the particles under alkaline conditions, following a proposed experimental plan (Table 1). As shown in Fig. 5, the hydrolysis does not change the overall spherical morphology of the final particles. However, depending on the experimental condition, particles form aggregates. Even so, hydrolyzed polymer samples present good stability at room temperature, keeping its spherical shape for several months, when stored at room temperature.

Table 2 shows the main properties of the PVAc/PVA particles synthesized using different hydrolysis conditions. In relation to the particle size, as observed experimentally, when the modification reaction is performed to form the PVA shell, deviation to higher values takes place. Similar effects were reported previously when PVAc copolymers were synthesized with the same technique [34]. As with the milling process, applied to disaggregate macroscopic lumps, does not generate fragments (as verified through optical microscopy) and particle size present a similar behavior, increasing of the final PVAc/PVA particle sizes are probably due to the consumption of small particles (0.1 to 1 [micro]m) in the aqueous medium, as observed previously in Figure 2. The hydrolysis of PVAc leads to formation of PVA and partial dissolution of the hydrolyzed polymeric material. Small particles are certainly more sensitive to the hydrolysis (given the lower volume and swollen diffusive resistance to caustic treatment) and PVA dissolution. For this reason, the particle size distribution becomes narrower and the effects are more pronounced when the hydrolysis is more severe, especially at high temperatures. This effect can be very important when one is interested in producing embolic agents, as particle size are constitute a fundamental property of the final product.

In theory, the hydrolysis reaction is expected to cause the decrease of the final molecular weight averages of the polymers, due to the cleavage of the acetate groups (Fig. 6). Table 2 shows that the number-average values ([M.sub.n]) decreased considerably for all samples when compared to the original PVAc ([M.sub.n] = 125 kg/mol). This reinforces that significant modification of the molecular properties take place. However, simultaneously with this effect, a relative small increase of weight-average ([M.sub.w]) values, in relation to the original PVAc ([M.sub.w] = 233 kg/ mol), was also observed in all trials, leading to a pronounced increase of the polydispersity ([M.sub.w]/[M.sub.n]). This effect is shown in Fig. 7, where a broadening of the molecular weight distribution can be easily observed.

As observed before Ref. 21, formation of polymer branches through transfer to polymer is usual in VAc polymerizations. In general, the branching frequency increases with temperature, reaction time, and residual monomer content. Therefore, during the PVAc hydrolysis, one may expect the formation of larger polymer chains through branching, lower polymer chains through hydrolysis, cleavage, and as a consequence, increase of the polydispersity index ([M.sub.w]/[M.sub.n]). These effects were observed in all hydrolyzed samples (Table 2) and help to explain the changes in the molecular weight properties of the obtained PVAc/PVA. However, given the low PVA content of the final polymer samples, modification of the molecular weight distribution cannot be assigned only to the hydrolysis effect, but also to radical reactions during the hydrolysis step. In fact, standard empirical regression analysis showed that the NaOH concentration, the reaction time, and third-order interaction (term [X.sub.1][X.sub.2][X.sub.3]) exert significant influence on the [M.sub.w] of the polymers. This might already be expected, as the alkali concentration and the reaction time can be regarded as the most important variables in the hydrolysis reaction. However, the significant effect of the third-order interaction on the molecular properties suggests a more complex reaction control the evolution of the molecular weight distributions of the final polymer material.

Table 2 also shows results the thermal behavior of the PVAc/PVA samples synthesized. The obtained results show that the [T.sub.g] values of the hydrolyzed copolymers are very similar to the [T.sub.g] of the original PVAc (42.31[degrees]C). In fact, the empirical regression analysis performed shows that, in this studied range, none of the analyzed variables exert a significant influence on the final [T.sub.g] value. Therefore, the obtained results indicate (Table 2) that the PVA shell does not contain more than 2 wt% of the PVAc/PVA copolymer. These results are in good agreement with previous published work [30], where the PVA shell constitutes a very thin layer at the surface of the particles. Thus, if one is interested in increasing the extent of hydrolysis (and also the PVA content of the final polymer particle), more aggressive saponification conditions should be applied, such as longer reaction times and higher alkali concentrations [22, 25, 26]. Although standard regression analysis does not indicate any significant effect on the [T.sub.g] of the obtained copolymers, reaction temperature seems to affect the final degree of hydrolysis, as the average degree of hydrolysis is higher at the higher analyzed temperatures.

It must be emphasized that increased PVA contents are not pursued here, as they are not necessary for good embolization performances. Although some recent works attempted to produce pure PVA spherical particles with high crystallinity [26], a thin layer of PVA seems to be sufficient to guarantee the biocompatibility of the particle. In addition, it is important to emphasize that, for embolic and also chemoembolic agents, it is desirable that the spherical particles with core-shell morphology present a considerable content of PVAc. This is because the PVAc core can provide the "low" [T.sub.g], allowing for the particle to deform inside the blood vessel, and adjust its shape to promote the more efficient physical occlusion of the blood vessel, as observed previously by in vivo tests [21, 29].

PVAc/PVA copolymers were also produced using alternative reaction conditions, not included in the original experimental plan presented in Table 1. These conditions included longer reaction times (15-24 h), higher temperatures (80[degrees]C), and also higher alkali concentrations (combining NaOH and methanol). Although the use of caustic solutions of methanol constitutes a common strategy to perform the hydrolysis of PVAc into PVA [24, 25], the simultaneous combination of the more aggressive reaction conditions promoted complete hydrolysis of the polymer material and loss of the well-defined spherical particle morphology, which is not desired for embolization procedures. As expected, this showed that proper variation of the reaction conditions could provide higher degrees of hydrolysis, if necessary. However, it is important to emphasize that since methanol presents a high toxicity in humans, its use to produce medical devices are usually avoided to reduce the risk of contamination by residual molecules in the final product.

X-ray Diffraction (XRD) analyses were performed to identify the crystalline characteristics of the PVAc and PVAc/PVA spherical particles. As expected and show in Fig. 8, the PVAc synthesized through free-radical suspension polymerization presented two very broad Bragg diffraction peaks in the region 2[theta] = 7-30[degrees], which can be related to the amorphous structure of the polymer matrix. In contrast, PVA commercial samples presented a completely different XRD diffractogram, which can be associated with a semi-crystalline polymer structure, emphasized by accentuated Bragg diffraction peaks at 19.3[degrees] and 22.5[degrees], values in agreement to PVA Bragg diffraction data reported in the literature [26], PVAc/PVA samples presented in general XRD diffractograms that were very similar to the ones observed for the PVAc particles, which can be related to the amorphous PVAc-rich copolymer blend, with a large Bragg diffraction in the region between 2[theta] = 7-30[degrees], confirming that the degree of hydrolysis was very small in the analyzed experimental range (Table 2).


Spherical and stable PVAc particles were prepared through free-radical suspension polymerization of VAc and submitted to different hydrolysis conditions for production of spherical core-shell particles, with a PVAc core and a PVA shell. In order to evaluate the real effects of the hydrolysis reaction on the final morphology and molecular properties of particles, the core (PVAc) and the shell (PVA) were synthesized as two independent steps. In relation to the core, it was possible to obtain spherical and stable PVAc particles through suspension polymerization of VAc by achieving high monomer conversions and high molecular weight values. The PVA shell was synthesis using different reaction conditions, based on an experimental plan. It was shown that none of the conditions studied affected the overall morphology of the final particle, although consistent shift of particle diameters could be observed to larger diameter values, probably due to solubilization of the smaller particles. However, alkali concentration and reaction time (and also reaction temperature) exert significant effects on the final molecular properties of the produced PVAc/PVA particles, leading to decrease of the number-average molecular weight (due to hydrolysis and cleavage), increase of weight-average molecular weight (due to chain transfer to polymer), broadening of the molecular weight distribution. Finally, the synthesized PVAc/PVA particles are essentially amorphous and present very low PVA content (lower than 2%), which is suitable for use as embolic and chemoembolic agents.


The authors thank Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq, Brazil) for financial support and scholarships. Part of this work was previously presented in a poster section at the XVIII Congresso Brasileiro de Engenharia Quimica (Foz do Iguacu, Brazil, 2010).


[1.] K.E. Uhrich, S.M. Cannizzaro, R.S. Langer, and K.M. Shakesheff, Cliem. Rev., 99, 3181 (1999).

[2.] C.C. DeMerlis and D.R. Schoneker, Food Chem. Toxicol., 41, 319 (2003).

[3.] T. Borovac, J.P. Pelage, A. Kasselouri, P. Prognon, G. Guiffant, and A. Laurent, J. Control. Release, 115, 266 (2006).

[4.] M.P. Stevens, Polymer Chemistry--An Introduction. 3. ed., Oxford University Press, New York (1999).

[5.] N.S. Banu and I.T. Manyonda, Curr. Obstet. Gynecol., 14, 327 (2004).

[6.] S. Kadir, Selected Techniques in Interventional Radiology, W.B. Sunders, London (1982).

[7.] S.J. Smith, Am. Fam. Physician, 61, 3601 (2000).

[8.] T. Kato, R. Nemoto, H. Mori, and I. Kumagai, Cancer, 46, 14 (1980).

[9.] T. Kato, R. Nemoto, H. Mori, M. Takahashi, and M. Harada, Cancer, 48, 674 (1981).

[10.] S. Wallace, C. Charnsangavej, C. Carrasco, and W. Bechtel, Cancer, 54, 2751 (1984).

[11.] N. Kisilevzky and M. Martins, Radiol. Bras., 36, 129 (2003).

[12.] A. Berenstein and E. Russell, Radiology, 141, 105 (1981).

[13.] M.J. Kang, J.M. Park, W.S. Choi, J. Lee, and B.K. Kwak, Chem. Pharm. Bull., 58, 288 (2010).

[14.] R. Beaujeux, A. Laurent, M. Wassef, A. Casasco, Y.P. Gobin, A. Aymard, D. Rufenacht, and J.J. Merland, Am. J. Neuroradiol., 17, 541 (1996).

[15.] A.L. Lewis, M.V. Gonzalez, S.W. Leppard, J E. Brown, P.W. Stratford, G.J. Phillips, and A.W. Lloyd, J. Mater. Sci.-Mater. M., 18, 1691 (2007).

[16.] M.V. Gonzalez, Y. Tang, G.J. Phillips, A.W. Lloyd, B. Hall, P.W. Stratford, and A.L. Lewis, J. Mater. Sci.-Mater M., 19, 767 (2008).

[17.] N.M. Bikales, Encyclopedia of Polymer Science and Technology: Plastics, Resins, Rubbers and Fibers, John Wiley & Sons, New York (1971).

[18.] C.A. Finch, Polyvinyl Alcohol--Properties and Applications, John Wiley & Sons, Bristol (1973).

[19.] I. Sakurada, Polyvinyl Alcohol Fibers. 1. ed., Marcel Dekker, Inc, New York (1985).

[20.] F. Turjman, T.F. Massoud, H.V. Vinters, C. Ji, M. Tardy, G. Guglielmi, and F. Vihuela, Am. J. Neuroradioi, 16, 1031 (1995).

[21.] L.S. Peixoto, F.M. Silva, M.A.L. Niemeyer, G. Espinosa, P.A. Melo, M. Nele, and J.C. Pinto, Macromol. Symp., 243, 190 (2006).

[22.] C.J. Kim and P. Lee, Pharmaceut. Res., 9, 10 (1992).

[23.] S.G. Lee, J.P. Kim, I.C. Kwon, K.H. Park, S.K. Noh, S.S. Han. and W.S. Lyoo, J. Polym, Sci. Pol. Client., 44, 3567 (2006).

[24.] S.G. Lee and W.S. Lyoo, J. Appl. Polym. Sci., 107. 1701 (2007).

[25.] H.M. Jung, E.M. Lee, B.C. Ji, Y. Deng, J.D. Yun, and J.H. Yeum, Colloid Polym. Sci., 285. 705 (2007).

[26.] V. Semenzim, G. Basso, D. Silva, A. Vasconcellos, G. Agreli, A.L. Oliveira, R.K. Oyama, D. Braile, and J. Nery, J. Appl. Polym. Sci., 121, 1417 (2011).

[27.] G.R. Ferreira, T. Segura, F.G. Souza, A.P. Umpierre, and F. Machado, Eur. Polym. J., 48, 2050 (2012).

[28.] J.C. Pinto, WO 2006/050591 A2 (2006).

[29.] W.D.S. Mendes, V.L.A. Chagas, J.C. Pinto, J.G. Caldas, and G. Espinosa, Rev. Col. Bras. Cir., 32, 120 (2005).

[30.] L.S. Peixoto, P.A. Melo, M. Nele, and J.C. Pinto, Macromol. Mater. Eng., 294, 463 (2009).

[31.] L.S. Peixoto, F. Cordeiro, P.A. Melo, M. Nele, and J.C. Pinto, Macromol. Symp., 299-300, 132 (2011).

[32.] M.A.M. Oliveira, P.A. Melo, M. Nele, and J.C. Pinto, Macromol. Symp., 299-300, 34 (2011).

[33.] M.A.M. Oliveira, P.A. Melo, M. Nele, and J.C. Pinto, Macromol. Symp., 319, 23 (2012).

[34.] M.A.M. Oliveira, P.A. Melo, M. Nele and J. C. Pinto, Macromol. React. Eng., 6, 280 (2012).

[35.] M. Oliveira, B.S. Barbosa, M. Nele, and J.C. Pinto, Macromol. React. Eng., 8, 493 (2014).

[36.] G. Moad and H. Solomon, The Chemistry of Radical Polymerization, Elsevier, Oxford (2006).

[37.] C. Barner-Kowollik, Handbook of RAFT Polymerization, Wiley-VCH, Sydney (2008).

[38.] A. Favier, C. Barner-Kowollik. T.P. Davis, and M.H. Stenzel, Macromol. Client. Physic., 205, 925 (2004).

[39.] R.L. Worthington-Kirsch, G.A. Fueredi, S.C. Goodwin, L. Machan, G.A. Niedzwiecki, J.F. Reidy, J.B. Spies, and W.J. Walker, Radiology, 218, 605 (2001).

[40.] P. Bastian, R. Bartkowski, H. Kohler, and T. Kissel, Eur. J. Pharm. Biopharm., 46, 243 (1998).

[41.] H.G. Yuan, G. Kalfas, and W.H. Ray, J. Macromol. Sci. R. M. C., 31, 215 (1991).

Marco Oliveira, Leilane Carla Matos Cirilo, Marcio Nele, Jose Carlos Pinto

Programa de Engenharia Quimica/COPPE, Universidade Federal do Rio de Janeiro, Cidade Universitaria--CP 68502, Rio de Janeiro, RJ 21941-972, Brazil

Correspondence to: J.C. Pinto; e-mail:

DOI 10.1002/pen.24109

TABLE 1. Experimental plan to conduct the partial hydrolysis of PVAc.

                          Time    Temperature
Exp   Run   NaOH(M) (a)   (min)   ([degrees]C)   X1   X2   X3

1      7        15         120         80        +1   +1   +1
2      6         5         120         80        -1   +1   +1
3     10        15         30          80        +1   -1   +1
4      2         5         30          80        -1   -1   +1
5      9        15         120         30        +1   +1   -1
6      3         5         120         30        -1   +1   -1
7      1        15         30          30        +1   -1   -1
8      5         5         30          30        -1   -1   -1
9     11        10         75          55        0    0    0
10     4        10         75          55        0    0    0
11     8        10         75          55        0    0    0

(a) Final concentration in reaction medium = 1, 2 or 3 M.

TABLE 2. Morphological and molecular properties of PVAc/PVA
particles synthesized based on the proposed experimental

                Codified variables

Exp    [X.sub.1]   [X.sub.2]   [X.sub.3]

1         +1          +1          +1
2         -1          +1          +1
3         +1          -1          +1
4         -1          -1          +1
5         +1          +1          -1
6         -1          +1          -1
7         +1          -1          -1
8         -1          -1          -1
9          0           0           0
10         0           0           0
11         0           0           0

                      Particle size ([mu]m)

Exp    Num (a)   [PDI.sub.num]   Vol (b)   [PDI.sub.vol]

1       192.2         1.8         701.0         1.2
2       189.5         2.0         786.3         1.2
3       190.5         2.0         742.7         1.2
4       459.0         1.1         691.1         1.1
5       144.1         1.8         563.8         1.3
6       174.2         2.0         619.0         1.2
7       143.3         1.8         543.7         1.2
8       145.7         1.9         552.4         1.2
9       149.6         1.8         554.8         1.2
10      141.0         1.8         510.9         1.2
11      226.2         1.7         607.0         1.2

            Molecular weight (kg/mol)

Exp    [M.sub.n]   [M.sub.w]   [M.sub.n]

1        42.2        203.4        4.8
2        54.7        206.7        3.8
3        49.7        237.6        4.8
4        27.1        161.3        6.0
5        51.6        271.3        5.3
6        36.1        193.6        5.4
7        43.0        197.5        4.6
8        54.0        205.1        3.8
9        46.2        244.1        5.3
10       53.8        243.9        4.5
11       46.6        253.5        5.4

        [T.sub.g]     Hydrolysis
Exp    ([degrees]C)     (wt%)

1          42.5          0.5
2          42.7          1.0
3          42.6          0.8
4          42.6          0.8
5          42.0          0.0
6          42.3          0.0
7          42.1          0.0
8          41.8          0.0
9          42.3          0.0
10         42.4          0.4
11         42.2          0.0

Average value of n = 2.
PDI: Polydispersity index for particle size.
(a) Numerical particle size.
(b) Volumetric particle size.
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Author:Oliveira, Marco; Cirilo, Leilane Carla Matos; Nele, Marcio; Pinto, Jose Carlos
Publication:Polymer Engineering and Science
Article Type:Report
Geographic Code:3BRAZ
Date:Oct 1, 2015
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