pla - em dioxano - tips - 2005

Journal of Membrane Science 238 (2004) 6573

Formation of poly(l-lactic acid) microfiltration membranesvia thermally induced phase separation

Takaaki Tanaka a,, Douglas R. Lloyd ba Department of Materials Science and Technology, Niigata University, Niigata 950-2181, Japan

b Department of Chemical Engineering, The University of Texas at Austin, Austin, TX 78712, USAReceived 10 November 2003; received in revised form 16 March 2004; accepted 16 March 2004

Available online 11 May 2004

Abstract

Microfiltration membranes of poly(l-lactic acid) (PLLA) were prepared from PLLA1,4-dioxanewater solutions via the thermally inducedphase separation process. Ternary phase diagrams for this system, determined at 10, 48, and 80 C, indicate that essentially polymer-freedroplets form in a matrix phase of PLLA1,4-dioxanewater solution. Rapid solidification of the PLLA after the initial liquidliquid phaseseparation was necessary to obtain membranes with open pores at the membrane surface and low permeation resistance. Using filtration ofcell suspensions, the effective pore size of the best membrane formed in this study was found to be between 0.6 and 4.4m. 2004 Elsevier B.V. All rights reserved.

Keywords: Poly(l-lactic acid); Microfiltration membrane; Phase separation; Biodegradable plastics; Permeability

1. Introduction

Until the late 1980s, application of poly(l-lactic acid)(PLLA) was limited to medical uses because of its high price.However, decreases in the production cost of l-lactic acidand improvements in the polymerization process have led tothe commercial-scale production of PLLA for non-medicalapplications, such as packaging films, containers, and fibers[1,2]. PLLA offers two distinct advantages over conventionalpolymers. First, PLLA is produced from a monomer that canbe produced by lactic acid bacteria using agricultural prod-ucts and by-products. Therefore, unlike most commercialpolymers, the cost of PLLA is not dependent on the produc-tion and price of oil. Since the feedstock for the polymer isannually renewable, the use of PLLA will help reduce theemission of fossil fuel-derived CO2 [1]. Second, PLLA isbiodegradable in vivo [3], in the environment [4] and in com-post [2]. High molecular weight PLLA is rarely effected byfungi, mold, or other microbes at ordinary temperatures, butit can readily be converted into compost in municipal com-post facilities at high temperatures (5570 C) and high hu-

Corresponding author. Tel.: +81-25-262-7495;fax: +81-25-262-7495.

E-mail address: [email protected] (T. Tanaka).

midity. Upon disposal, PLLA is degraded initially by chemi-cal hydrolysis, not microbial attack. Oligomers of lactic acidserve as a catalyst for the hydrolysis of PLLA in abioticdegradation [3], while some enzymes [5] and microorgan-isms [4] enhance the rate of the degradation of the polymer.To help establish a green sustainable society, wider use ofbiodegradable polymers such as PLLA is desired. If PLLAis used for microfiltration membranes in food and biochem-ical industries, where microfiltration is a key processes ofclarification and cell recovery, the membrane can be com-posted after use.

Porous PLLA membranes have been developed previ-ously to serve as the scaffold for human cell growth in tissueengineering and as the support for the controlled release ofmedicines. These porous structures were made by a varietyof methods: use of a porogen, dry phase inversion, immer-sion precipitation, and thermally induced phase separation.In the porogen method, a solution of PLLA in chloroform ormethylene chloride containing sieved salt crystals (sodiumcitrate, NH4Cl, NaCl) is cast on a plate. The film formedafter the evaporation of the solvent was washed with water.The spaces occupied by the salt crystals turn into the pores[3,6,7]. These porous membranes are suitable for scaffoldingof mammalian cells but not for microfiltration membranesbecause the pores are several hundred micrometers. In the

0376-7388/$ see front matter 2004 Elsevier B.V. All rights reserved.doi:10.1016/j.memsci.2004.03.020

66 T. Tanaka, D.R. Lloyd / Journal of Membrane Science 238 (2004) 6573

dry phase inversion method, porous membranes are made byevaporating the solvent from a solution of PLLA in acetoneor methylene chlorideethyl acetate [8,9]. In the preparationof porous PLLA structures by the immersion precipitationmethod, 1,4-dioxane, chloroform, N-methyl pyrrolidone, oracetone was used as the solvent while water, methanol, orethanol was used as the nonsolvent in a ternary casting so-lution [10,11]. Thermally induced phase separation [12,13]has also been applied to make porous PLLA membranes.In this method 1,4-dioxane [14,15] or 1,4-dioxane plus wa-ter [16,17] served as the diluent. Solutions of PLLA wereprepared at an elevated temperature, cooled to induce phaseseparation, and then freeze dried. Alternatively, solutions ofPLLA in phenol, naphthalene [18], or methylene chlorideplus ethyl acetate [19,20] were heated, cooled to room tem-perature, and then dried to produce PLLA foams. PorousPLLA structures have also been obtained by blending PLLAand poly(ethylene oxide) in chloroform, drying off the chlo-roform, and extracting the poly(ethylene oxide) with water[21]. In these previous studies the morphology of the mem-branes have been observed by scanning electron microscopyand the pore-size distribution of some of the membraneshave been measured by mercury porosimetry. However,these membranes have not yet been used for microfiltration.

In the study reported here, microfiltration membraneswere prepared from ternary mixtures of PLLA1,4-dioxanewater via the thermally induced phase separation method,and they were characterized for permeation resistance andretention of microbial cells.

2. Experimental

2.1. Materials

PLLA was a gift from Shimadzu Corp. (Kyoto) and Toy-ota Motor Corp. (Nagoya). The weight average molecularweight, melting point, and glass transition temperature were1.87 105 (Mw/Mn = 2.4), 175.4 C, and 62.8 C, respec-tively, according to the data sheet from the manufacturer. An-alytical grade 1,4-dioxane (bp = 101.4 C, mp = 11.8 C)was used without further purification.

2.2. Phase diagrams

As mentioned above, 1,4-dioxane (solubility parameter =10.0 cal0.5/cm0.5 [20.5 MPa0.5]) has been used to dissolvepoly(lactic acid) (solubility parameter = 10.010.3 cal0.5/cm0.5 [20.521.1 MPa0.5]) [23] for the preparation of mem-branes. The cloud point of PLLA1,4-dioxane system de-creases from the freezing point of 1,4-dioxane (11.8 C)as the PLLA concentration is increased [15]. This type ofphase diagram indicates that solidliquid phase separationwill occur when the solution is thermally quenched. How-ever, when water (which is miscible with 1,4-dioxane, but isa non-solvent for PLLA) is added to the PLLA1,4-dioxane

solution, the shape of the phase diagram changes to yield atwo-phase liquidliquid region [16,17,22]. Because water isa non-solvent for PLLA but is miscible with 1,4-dioxane, ithas also been used as the coagulation bath in the prepara-tion of PLLA porous materials via immersion precipitation(nonsolvent induced phase separation) [10,22,24,25].

PLLA was dissolved in a 1,4-dioxanewater mixture in a100 or 125 cm3 flask, sealed with a cork stopper which hadbeen covered with aluminum foil and polytetrafluoroethy-lene tape. The polymer concentration and the water con-tent in the diluent were 120 and 1115 wt.%, respectively.PLLA was first dissolved in 1,4-dioxane at 8090 C on astirrer/hot plate (Model PC-420, Corning, New York, NY)and then water was added. After dissolution, the solutionwas kept at 80 C for more than 30 min by placing the sealedflask in an oven. The solution was then placed in a waterbath at 2080 C and held at that temperature for a periodof ten minutes. The cloud point temperature was defined inthis study as the temperature at which the solution turnedcloudy during the 10 min period, having been clear duringthe 10 min hold time at a temperature 1 C above the cloudpoint temperature. The ternary phase diagram was deter-mined by the method shown by van de Witte et al. [22].

Tie lines at 48 C were determined as follows. A mix-ture containing 2.00 g of PLLA, 40.80 g of 1,4-dioxane, and7.20 g of water (total weight = 50.00 g) was prepared at80 C in a 100 cm3 flask as described above. After becom-ing clear and homogeneous, the mixture was moved to awater bath at 48 C and kept there for 30 min. It was thenkept at 48 C in an incubator for 1224 h. During this timethe mixture separated into two clear but distinct phases. Thetop (polymer-lean) phase was recovered with a pipette intoa glass beaker in the incubator. The pipette and beaker werepreheated at 48 C for more than 30 min before use. Theweight of the bottom (polymer-rich) phase was calculatedfrom the difference between the weight of the total sampleand the top phase. Since the phase diagram indicated thatthe top phase was essentially polymer-free, it was assumedthat all of the polymer was in the bottom phase. Therefore,the polymer concentration in the bottom phase was calcu-lated from the initial mass of the polymer in the mixture andthe mass of the bottom phase. The polymer concentrationso determined was used to represent the bottom phase onthe binodal at 48 C. The tie line was drawn to pass throughthe composition of the bottom phase and the initial compo-sition (not shown) and is extended to the polymer-free axis.Another tie line was determined with a mixture containing5.00 g of PLLA, 38.70 g of 1,4-dioxane, and 6.30 g of water.

2.3. Membrane formation

PLLA membranes were prepared in an apparatus (Fig. 1)composed of three stainless steel pie pans (22.8 cm in di-ameter, G&S Metal Products Co., Cleveland, OH). The ap-paratus was preheated in an oven for 15 min before use. APLLA solution (10 wt.%) in a mixed diluent of 1,4-dioxane

T. Tanaka, D.R. Lloyd / Journal of Membrane Science 238 (2004) 6573 67

Fig. 1. Apparatus for membrane preparation.

and water (87:13) was kept in a sealed flask at 80 C formore than 30 min. The solution (approximately 40 cm3) waspoured into the bottom pan. The solution was covered withthe middle pan and kept at 80 C for 5 min. The distance be-tween the bottom and middle pan was maintained at 0.8 mmthrough the use of four metal spacers. A third pan was placedover the middle pan as shown and the solution was keptat 80 C for 10 min. The top pan protected the middle panfrom any thermal conduction effects caused by the air in theroom. The apparatus was cooled for 5 min in a water bathat 50 C and then quenched to 0 C in an ice water bath for1 h. The gel formed by this method was washed with chilledwater to remove the diluent. After the three times of wash-ing (100, 800 cm3, and 1 dm3 of water) the membranes didnot smell of 1,4-dioxane. The resulting porous membraneswere kept in water before characterization.

2.4. Scanning electron microscopy (SEM)

The wet membrane was immersed in liquid nitrogen andthen fractured. It was mounted vertically on a sample holder.The surface of the sample was coated with goldpalladiumusing a sputter coater (EMS 575, Electron Microscopy Sci-ence, Fort Washington, PA). A scanning electron microscope(S-4500II, Hitachi, Tokyo) with an accelerating voltage of15 kV was used to examine the membrane cross-sectionsand surfaces.

2.5. Filtration experiments

A filtration cell (Amicon model 8010, 4.1 cm2, Millipore,Bedford, MA) was used without its stirrer for dead-end fil-tration experiments. Water was used to measure the perme-ation resistance of membranes. The filtration was performedat a transmembrane pressure drop of 30 kPa and at 2225 C,where the viscosity of water is 1 103 Pa s. Microbialcells of bakers yeast (Fleishmanns active dry yeast, Fen-ton, MO) and Escherichia coli MC4100 were used to exam-ine the retention of microorganisms by the membranes. Theyeast cells were suspended in distilled water at a concentra-tion of 10 kg/m3 as dry yeast powder, which corresponds toa cell concentration of 24 kg-wet/m3 and 7 kg-dry/m3. A cellsize of (5.61.1)(4.40.8)m was determined by mea-suring the long and short axes of 100 cells under an opticalmicroscope. The E. coli was cultivated for 12 h in 400 cm3

of L broth in a 2 dm3 flask. The cells were recovered bycentrifuge and suspended in the same volume of distilledwater. The cell concentration was 3.5 kg-wet/m3, which cor-responds to 1.0 kg-dry/m3. The cell size was 1.060.20min length and 0.63 0.04m in diameter as determinedby measuring the length and diameter of 100 cells under ascanning electron microscope.

3. Results and discussion

3.1. Phase diagram

Fig. 2(a) shows the effect of the PLLA concentrationon the cloud point temperature of the solutions of PLLAin 1,4-dioxane containing water at different concentrations(1115 wt.%). The cloud point temperature increased lin-early with increasing polymer concentration for each watercontent. It also increased linearly when the water contentin the diluent was increased at the same PLLA concen-tration (Fig. 2(b)). The phase behavior of the PLLA1,4-dioxanewater system was similar to the results reported byvan de Witte et al. [22] for the same system, although thecloud point temperatures reported here are slightly higher.

Fig. 2. Cloud point temperatures of PLLA1,4-dioxanewater system.Dependence on the PLLA concentration (a) and water content in diluents(b).


Fig. 3. Ternary phase diagram of PLLA1,4-dioxanewater system. Bro-ken lines are tie lines at 48 C. The black rhombus shows the compo-sition of the mixture of 10 wt.% PLLA in a mixed diluent of 87 wt.%1,4-dioxane and 13 wt.% water.

There is a possibility of hydrolysis of PLLA in1,4-dioxane containing water at 80 C. The cloud pointswill decrease when the molecular weight was lowered bythe hydrolysis [17,26]. However, the effect will be small onthe cloud points in this study since the temperatures did notchange when we checked some of them within 1 h.

Ternary phase diagrams of the PLLA1,4-dioxanewatersystem at different temperatures (Fig. 3) were obtainedfrom the data in Fig. 2(b) by the method reported byvan de Witte et al. [22]. The binodal shifted from thesolvent-rich area toward the nonsolvent-rich area with in-creasing temperature, indicating a decrease in system com-patibility with decreasing temperature. Fig. 4 schematicallyshows the mechanisms of phase separation for a ternarypolymersolventnonsolvent system undergoing thermallyinduced phase separation. As the homogeneous solutionis cooled, it starts to demix into two liquid phases at thecloud point temperature. When the polymer concentrationis greater than the critical point concentration, dropletsof the polymer-lean phase form in the ternary mixture atthe cloud point temperature. In the system reported here(see Fig. 3), the polymer concentration of the critical pointis less than 1 wt.% PLLA for temperatures in the range1080 C. Thus, the PLLA1,4-dioxanewater system un-dergoes liquidliquid TIPS and should produce a cellularporous membrane structure.

3.2. Membrane permeability

Fig. 5 shows the permeability of PLLA membranesformed by different ternary mixtures of PLLA1,4-dioxanewater. The permeation resistance was independent of thewater content in the diluent when the PLLA concentrationwas 10 wt.%. The resistance was lower than that of themembrane prepared from a solution containing 12 wt.%PLLA. However, these resistances are higher than thoseof commercially available microfiltration and ultrafiltration

Fig. 4. Thermally induced phase separation in a ternary system: (a) phasediagram on the tie line in (b); (b) isothermal ternary phase diagram atthe cloud point temperature.

membranes (109 to 1013 m1 as calculated from typicalreported permeability values of 1104 gal ft2 per day psi1[27] with water of viscosity 1 103 Pa s at room temper-ature).

Fig. 6 shows the dependence of the membrane resistanceon the temperature at which a solution of 10 wt.% PLLAin 1,4-dioxane containing 13 wt.% water was kept for 5 minbefore quenching. The resistance greatly decreased when thesolution was kept at 5052 C before quenching. The reasonfor this behaviour is discussed in the next section.

Fig. 5. Dependence of the membrane resistance on the water content indiluent.


Fig. 6. Dependence of the membrane resistance on the temperature beforequenching: PLLA = 10 wt.%; water content in diluent = 13 wt.%.

3.3. Membrane structure

Figs. 79 show the structure of membranes preparedfrom a solution of 10 wt.% PLLA in 1,4-dioxane contain-ing 13 wt.% water but with different thermal histories. The

Fig. 7. PLLA membrane prepared by quenching 10 wt.% PLLA solution in 1,4-dioxane containing 13 wt.% water from 80 to 0 C. (a)(c) Cross-sections(the top side is on the left-hand side): (a) overview; (b) near the top side; (c) near the center. (d) The top surface.

membranes were prepared as described in Section 2.3, butwith different intermediate temperatures. Specifically, themembranes were prepared by three methods. In Method A,the assembly shown in Fig. 1 was quenched directly from80 C into ice water. The membrane is shown in Fig. 7.In Method B, the assembly was lowered from 80 to 50 Cwhere it was held for 5 min and then quenched in ice wa-ter. The membrane is shown in Fig. 8. In Method C, theintermediate hold temperature was 30 C. The membraneis shown in Fig. 9. Each figure shows the cross-section(overview in (a), near the top surface in (b), and at the centerin (c)) and the top surface (in (d)). Micrographs correspond-ing to (b) and (d) taken at the bottom of the sample weresimilar to those taken at the top and are therefore not shownhere. The cell size in the central part of the membranesprepared by Methods A and B (Figs. 7(c) and 8(c)) wereessentially the same, with cells ranging from 3 to 10m.However, the surface and cross-section near the surface weresignificantly different for these two thermal histories. Thecells were greatly deformed and the pores were closed nearthe top surface of the membrane prepared by Method A(Fig. 7(b) and (d)), while the cells near the surface wereopen like those in the central part of the membrane when the


Fig. 8. PLLA membrane prepared by quenching 10 wt.% PLLA solution in 1,4-dioxane containing 13 wt.% water from 50 to 0 C: (a)(d) the same asin Fig. 7.

membrane was prepared by Method B (Fig. 8(b) and (d)).That is, Method A produces significant anisotropy in thesample while Method B produces a structure more closelyapproximating isotropic.

To explain the differences between Methods A and B, aseries of quench experiments were conducted to monitor thetemperature of the solution contained in the assembly shownin Fig. 1. In these experiments, 40 cm3 of water was placedin the assembly rather than polymer solution and the temper-ature was monitored using a thermocouple as the assemblywas quenched in ice water. Fig. 10 shows the temperatureof the water during the quench. In both cases the tempera-ture decreases rapidly and then reaches a final steady-statetemperature equal to the surrounding ice water. Fig. 10 hasa horizontal line at 48 C, which is the phase separationtemperature for the PLLA1,4-dioxanewater system usedto make the membranes shown in Figs. 79. Fig. 10 alsohas a horizontal line at 7 C, which is the solidification tem-perature of PLLA in this ternary system as explained inthe next paragraph. The membrane prepared via Method Adoes not phase separate until 40 s after the quench and itspends approximately 100 s between the time of phase sep-aration and solidification. On the other hand, the membrane

prepared via Method B phase separates almost immediatelyupon quenching and solidifies after 40 s. It is speculated thatthe droplets of polymer-lean phase deformed at the stain-less surfaces during the prolonged liquid period allowed inMethod A and resulted in closed cells upon solidification.Thus, the permeation resistance of the membrane preparedby Method A was much higher than that prepared by MethodB. This deformation of droplets at the metal surface may beassociated with spreading or wetting phenomenaa pointthat needs to be explored further in future research.

To provide the PLLA solidification temperature indicatedin Fig. 10, a series of experiments were conducted. Afterdissolving 10 wt.% PLLA in 1,4-dioxane containing 13 wt.%water at 80 C, 3 cm3 of the solution was placed in a 125 cm3flask where it formed a thin layer on the bottom of the flask.The flask was capped with a stopper and transferred from an80 C oven to a water bath at a predetermined temperature.When placed in a bath at 10 C the solution became cloudy,but remained fluid for more than 9 min. When the flask wasplaced in a bath at 8 C, it solidified within 9 min, while ittook only 3 min in a 7 C bath. These results indicate thatthe solidification rate is extremely sensitive to temperature,especially around 7 C.


Fig. 9. PLLA membrane prepared by quenching 10 wt.% PLLA solution in 1,4-dioxane containing 13 wt.% water from 30 to 0 C: (a)(d) the same asin Fig. 7.

The pore size of the membrane prepared by holding the as-sembly at 30 C before quenching (Method C, Fig. 9(a)(c))was 1030m. In this case, the polymer-lean phase dropletsformed and coalesced during the pre-cooling at 30 C. For

Fig. 10. Thermal history of liquid within membrane preparation apparatus.The temperature was measured with 40 cm3 of water at the center of thetop surface of the middle pan.

the reasons outlined above, this prolonged period within thetwo-phase region allowed the droplets to distort and a densepolymer layer to form near both the top surfaces (Fig. 9(b)),which resulted in high permeation resistance.

The structures shown in Figs. 79 and the dependence ofthe membrane resistance on the temperature before quench-ing (Fig. 6) suggest that rapid solidification of the PLLA af-ter phase separation is necessary to obtain open pores at themembrane surfaces. This statement is in keeping with theobservations made when studying structure difference ob-tained using the immersion precipitation method of makingmembranes [28], in which delayed demixing of a polymersolution in a coagulation bath forms a nonporous layer onthe membrane surface while instantaneous demixing resultsin open pores on the surface.

3.4. Filtration of microbial cell suspensions

Suspensions of bakers yeast and E. coli cells were fil-tered with the membrane prepared by Method B to evaluateit as a microfiltration membrane. Fig. 11(a) shows the per-meation flux for the filtration of the yeast cell suspension,


Fig. 11. Permeation flux in microfiltration of yeast cell suspension witha PLLA membrane: (a) permeation flux; (b) a plot of reciprocal ofpermeation flux vs. permeation volume per unit filtration area. Cellconcentration = 24 kg-wet/m3; transmembrane pressure = 29 kPa.

for which a transparent permeate was obtained. The yeastcells were recovered 96% on the membrane. The changein permeation flux with time was converted to a plot ofthe reciprocal of the flux versus the permeate volume perunit filtration area (Fig. 11(b)). The linear relationship be-tween the reciprocal of flux and the permeate volume showsthat the filtration proceeded according to the cake filtrationmodel [29]. On the other hand, E. coli cells were not re-tained by the membrane (the recovery on the membrane =0%). These results indicate that the effective pore size of themembrane was between the size of the yeast (ellipsoidal,4.4m in short diameter) and E. coli (rod-shaped, 0.6m indiameter).

4. Conclusions

PLLA microfiltration membranes were prepared fromPLLA1,4-dioxanewater solutions via the TIPS process.Quick solidification of the PLLA in the polymer-rich phaseafter liquidliquid phase separation was necessary to obtainmembranes with low permeation resistance. The effectivepore size of the membrane formed using the thermal historydescribed as Method B in this study was between 0.6 and4.4m.

Acknowledgements

The authors thank Shimadzu Corp. and Toyota MotorCorp. for the kind gift of poly(l-lactic acid). The study waspartially supported from the grant of the Niigata Engineer-ing Promotion Inc. and Grants-in-Aid (15560673) for Sci-entific Research from the Japan Society for the Promotionof Science, Ministry of Education, Culture, Sports, Science,and Technology, Japan, to T. Tanaka. We thank Dr. YasuakiKawarasaki of Nagoya University and Prof. George Geor-

giou of The University of Texas at Austin for the cultivationof E. coli cells.

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Formation of poly(l-lactic acid) microfiltration membranes via thermally induced phase separationIntroductionExperimentalMaterialsPhase diagramsMembrane formationScanning electron microscopy (SEM)Filtration experiments

Results and discussionPhase diagramMembrane permeabilityMembrane structureFiltration of microbial cell suspensions

ConclusionsAcknowledgementsReferences

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