Novel Strategy of Lactide Polymerization Leading to Stereocomplex

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A novel strategy of Lactide polymerization leading to stereocomplex polylactide nanoparticles using supercritical fluid technology Gulnaz Bibi, Youngmee Jung, Jong-Choo Lim , and Soo Hyun Kim ACS Sustainable Chem. Eng., Just Accepted Manuscript • DOI: 10.1021/ acssuschemeng.6b00446 • Publication Date (Web): 11 May 2016 Downloaded from http://pubs.acs.org on May 17, 2016

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ACS Sustainable Chemistry & Engineering

A novel strategy of Lactide polymerization leading to stereocomplex polylactide nanoparticles using supercritical fluid technology

Gulnaz Bibi1, 2, Youngmee Jung 2, 3, Jong-Choo Lim 1,* , Soo Hyun Kim 2, 3, 4,**

1

Department of Chemical and Biochemical Engineering, Dongguk University-Seoul, 3-26

Pil-Dong, Chung-gu, Seoul 100-715, Republic of Korea 2

Biomaterials Research Center, Korea Institute of Science and Technology, Seoul 136-791,

Korea 3

Korea University of Science and Technology, 113 Gwahangno, Yuseong-gu, Daejeon 305-

333, Korea 4

KU-KIST Graduate School of Converging Science and Technology, Korea University,

Seoul, 136-701, Korea **Corresponding author 1. Tel: +82-2-958-5343. Fax: +82-2-958-5308. Email: [email protected]

Abstract: The enantiomeric crystallization of polylactides has removed the limitations of innate poor thermal and mechanical properties of the homopolymers. The supercritical fluid technology is an emerging panoramic version of biomedical polymer synthesis and has proven to be a domineering substitute to toxic organic solvents. Herein, we report an intriguing, efficient and a novel polymerization process using supercritical dimethylether (sc-DME) for preparation of polylactides leading to the stereocomplex polylactide (s-PLA) nanoparticles. The process has generated high molecular weight homopolymers (Mn≥200,000gmol-1) starting from monomers which ultimately crystallized to a dry powder of s-PLA nanoparticles. The optimum processing

1 ACS Paragon Plus Environment


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parameters are: D/L-Lactide polymerization using sc-DME at 130°C, 400bar for 5hrs with a 30% monomer concentration, keeping the ratio [Monomer]: [Tin (II)2-ethylhexanoate]: [1Dodecanol] as 3000:1:1 while the stereocomplexation as sc-DME at 70°C, 350bar for 2hrs. We have investigated the effects of monomer concentration, molecular weights of homopolymers, times, temperatures and pressures on the degree of stereocomplexation. The degree of s-PLA was analyzed by DSC and XRD. The s-PLA has improved melting point and thermal degradation than homopolymers. The Young’s Modulus of s-PLA increased to 1.4GPa with Tensile strength (~ 43MPa) enhanced than homopolymers (~ 13MPa) with 3.2% elongation at break. The dry s-PLA powder shows a diversity of particle size ranging from 40nm to 600nm analyzed by SEM. The s-PLA finds potential applications in polymer nanofabrication, biomedical stents and encapsulation, melt-blending, solution casting and molding. Keywords. Supercritical fluid technology, Dimethyl ether, High molecular weight polylactides, stereocomplexed polylactide, Nanoparticle, Biocompatible.

Introduction The stereoselective crystallization of polylactides generates a stereocomplex polylactie (s-PLA) with benefits of tuned physical properties as compared to their parent polymers, for example, low thermal degradation, high mechanical performance, valuable packaging prerequisites and improved hydrolysis resistance.1-8 The s-PLA finds a variety of challenging applications, both in commercial and biomedical fields such as in automobiles, packaging and nanofabrication.9-11 Recently s-PLA copolymers have been used in bone implant, bone plate, cardiovascular tissue regenerating stents and drug delivery systems.10,11 2 ACS Paragon Plus Environment

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The Polylactide being a potential biocompatible candidate has been extensively explored. The detailed description of racemic crystallization and morphological aspects of stereocomplex polylactides and copolylactides have also been reported.12-17 Numerous research contributions have addressed the synthesis of s-PLA and their copolymers in batch process using various methods. However, preparing s-PLA from high molecular weight homopolymers has rather been challenging using trivial processing techniques such as melt blending and solution casting. The sPLA from the melt processing meet with the poor melt stability to trigger the restructuring of sPLA crystals after complete melting.18 The solvent casting is also a costly and time consuming method of s-PLA preparation.19 H. Tsuiji and Y. Ikada has contributed with their incredible research in exploring various aspects of the stereoselective interaction resulting into the stereocomplex formation of polylactides and their co-polymers by physical mixing of their solutions and melt blending techniques.12,13 An interesting approach to exclusive s-PLA synthesis was made recently by crystallizing s-PLA from linear and multi star stereo diblock polylactide homopolymers.20 The s-PLA prepration and succeeding memory study revealed the advantages of grafting PLA homopolymers on cellulose nanowhiskers.21 Thermally stable s-PLA have been synthesized from homopolymers with an unusual melting temperature (≥190°C) grafted on MWCNT.22 Ex-foliated graphene has been used for enhancing crystallization of sPLA nanocomposites prepared by meltblending.23 Metallury inspired, sintering of s-PLA powder resulted in the synthesis of tranparent s-PLA castings with improved physical properties in an intreseting study.24 The concept of s-PLA formation is used for studying various amphipolar drug systems containing PLA chain inserted in backbone of the polymers of interest.25 A fast and facile approach of supercritical fluid (SCF) technology was introduced since few years ago by



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our research group in this regard.26-29 We have established a processing technology using various supercritical fluids for stereocomplex formation of polylactide with or without co-solvents.26, 27 Our objective was to establish a system working in a semi continuous manner, starting from monomers D- and L-Lactide, synthesizing polymers PDLA and PLLA respectively, and then their racemic crystalization as nanoparticle stereocomplex PLA in a single processing step. The supercritical CO2 has a limitation of required solubility for polylactides as it needs additional cosolvent like Dicholromethane (DCM) to give admissible solubility to PLA for sterecomplex processing.26 However, despite of adding co-solvent DCM, the supercritical CO2 - DCM system does not provide enough solubility for Lactide polymerization26 desired for our designed process. To overcome the difficulties related to supercritical CO2, we have selected Dimethyl ether (DME) as an SCF medium for the excellent solubility of PLA. The DME also offers ease in s-PLA recovery due to the easy evaporation at room temperature to leave the dry nanoparticles of stereocomplex polylactide behind as the last step of this process. The DME is non-hazardous for being nonmutagenic, noncarcinogenic, nonteratogenic, and nontoxic.27,32,33 Critical parameters of DME are Tc = 126.9 °C and Pc = 54 bar. This study address a continuous process involving the polymerization and the sterereocomplexation of PLA using sc-DME.

Experimental Materials. D-Lactide and L-Lactide (Mw = 144.3 g/mol) were purchased by Purac America Inc. and used as such. Tin (II) 2-ethylhexanoate (Sn(Oct)2 ) and 1-dodecanol (purity 92.5%-100%) and Toluene (purity 99.9%) were purchased from Sigma-Aldrich. Tin (II) 2-ethylhexanoate and


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1-dodecanol were dissolved in Toluene prior to use. Dimethyl ether (Sigma-Aldrich, purity 99.9%) and N2 (Shin Yang Oxygen Industry, minimum purity 99.9%) were used as received.

Homopolymerization. All preparations were made in the drying room under excellent humidity check. The D-Lactide and L-Lactide along with Sn(Oct)2 and 1-dodecanol were added to the respective D-polymerizing and L-polymerizing 50 mL stainless steel high-pressure reactors, each equipped with a magnetic stirrer and electrical bend heaters. The weight ratio of monomer to scDME was 30:100 in both reactors. The reactors were set for 2 hrs of vacuum followed by nitrogen purging for 10 minutes. The reactors were heated to 40 °C, cooled down to room temperature and then vacuumed again for another hour followed by nitrogen purging for 10 min. The reactors were connected to a DME feed system, filled with compressed DME to 30 bar at 30 °C and then gradually heated and stirred till they reached to 130 °C to achieve a pressure of 400 bar for 5hrs. The monomer to DME concentrations, molecular weight, pressure, temperature, and time were also varied to get optimum reaction conditions. Stereocomplex Formation. As soon as the polymerization reaction finished, the hot contents of polymerization units were shifted to the stereocomplex formation unit manually, opening the high pressure valves simultaneously. The stereocomplex formation reactor was vacuumed and cooled to below room temperature previously to trigger the maximum transfer of the PLLA and PDLA from the polymerization units. After shifting the homopolymers, the stereocomplex formation unit was filled with additional DME to get a pressure of 50 bar at room temperature and allowed to process for s-PLA formation at the predetermined conditions. At the end of the reaction, the reactor was chilled with Ice-Acetone mixture. The DME was allowed to evaporate after opening the reactor.



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Characterization. The molecular weight of the polymers was determined by GPC (Viscotek model 302 TDA). The degree of s-PLA formation was measured by a modulated differential scanning calorimeter (modulated DSC 2910, TA Instrument). The heating rate was fixed at 10°C/min. X-ray diffraction spectra were recorded with a X-ray diffractometer Rigaku D/Max 2500 composed of Cu KR(λ = 1.54056Ao , 30 kV, 100 mA) source, a quartz monochromator, and a goniometric plate. Thermogravimetric analysis (TGA) was conducted on a Hi-Res TGA 2950 (TA Instrument) under N2 flow. The mechanical properties were measured on an Instron apparatus. For Tensile testing a film with specimen size 20 × 5 mm and 170 µm thick was prepared using the pressure instrument equipped with a heating block and Polyimide vacuum bag. The gage length was 10 mm, and the extension rate was 3 mm/min. The SEM images were obtained for dry s-PLA particles using FEI-Nova Nano SEM 200. The s-PLA particle size was analyzed by Dynamic Light Scattering (DLS) on EL-Z particle size analyzer.

Results and Discussion This study describes a polymerization starting from D- and L-Lactide monomers followed by stereocomplexation of polylactide conducted in sc-DME. The process starts with monomers and ends in s-PLA formation progressing through polymerization. We have assembled two main structural and functional units for this study. The polymerization unit comprised of two high pressure autoclaves, for PDLA and PLLA synthesis, respectively, and a s-PLA formation unit involving another high pressure autoclave. Both of these polymerization and s-PLA formation units were interconnected with and controlled by two high pressure valves (V3 and V4) as shown in Figure 1. In the first step of this study, we allowed polymerization of D- and L-Lactide in their respective high pressure autoclaves and in the second step on completion of polymerization time, 6 ACS Paragon Plus Environment

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without any delay, we have shifted these PDLA and PLLA as dissolved hot polymer solutions into the stereocomplexation unit where the s-PLA processing underwent at predetermined reaction conditions. At the end of the reactions, DME chilling process helped the safe material ejecting from the reactors. A pair of high pressure valves labeled as V1 and V2 in Figure 1 is used to control the DME concentration. The continuous process comprised of polymerization leading to stereocomplexation in sc-DME is economic as it does not imply any other solvent or co-solvent at any step during processing. It is a fast process, avoiding time spent in synthesis, purification and drying of homopolymers in batch preparations. This continuous s-PLA process converts monomers to high molecular weight polymers which eventually crystallized as the sPLA nanoparticles in a short time span according to the predetermined reaction conditions. We have varied processing parameters such as DME concentration, monomer to catalyst and initiator ratios, reaction times, temperatures and pressures to optimize D-/L-Polymerization. By this we meant to achieve our objective to get high molecular weight polymers with approximately enough solubility and viscosity to flow while dissolving in sc-DME. We also intended to get s-PLA nanoparticles with maximum degree of stereocomplexation in high yield. The supercritical fluids exhibit liquid like densities and gas like diffusivities.34 Solubility of the polymers in SCF correlates with its density. The SCF is an inert solvent for polymer and dispels the heat generated during polymerization.34 From the thermochemical studies on polymersolvent interactions, it is expected that for maximum solubility of polymer, the Hildebrand solubility parameter, δ of polymer and solvent should be similar.35 Although, δ can possibly be varied between gaseous and liquid like values keeping the temperatures at or above critical point of the SCF.35 Thus a small fluctuation in pressure can tune in large alteration in density and viscosity of SCF affecting solubility of polymers.



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Figure 1. Schematic illustration of continuous processing plant. Here P1, P2 and P3 represent pressure Gauge 1, 2 and 3. V1, V2, V3 and V4 represent high pressure valves 1, 2, 3 and 4. T1,T2 and T3 represent temperature controller 1, 2 and 3. S1, S2 and S3 represent magnetic stirrer 1, 2 and 3. R1, R2 and R3 represent High Pressure Reactor 1, 2 and 3, respectively. Black arrow represents flow of DME.

The D/L-Lactide monomers develop polar interactions with sc-DME to dissolve efficiently (DME has a dipole moment of 1.3 D27,36). The D/L-Lactide monomers were added with Stannous Octanoate and 1-Dodecanol as catalyst and initiator37 respectively to follow the well established Ring Opening Polymerization36. The polymerization was carried out in the D-Lactide and LLactide polymerization units simultaneously at various reaction conditions to give PDLA and PLLA polymers respectively. Unless the hot contents of the D/L-Polymerization units were shifted to the s-PLA formation unit, the PDLA and PLLA remain dissolved in sc-DME. As soon 8 ACS Paragon Plus Environment

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as the polymerization is accomplished, opening the high pressure valves allowed simultaneous quick transfer of the sc-DME-polymer mixtures from PDLA and PLLA polymerization units respectively to the s-PLA formation unit. The effects of temperature, pressure, time and concentration on the molecular weight of the homopolymers and the degree of stereocomplexation were also studied. In order to optimize the molecular weight of the homopolymers (PLLA and PDLA), we have conducted D-/L-Lactide polymerization in batch. (Note: The D-/L-Lactide polymerization in continuous processing was conducted at optimized reaction conditions obtained in batch polymerization.) The effects of different parameters on the molecular weights of PLA homopolymers and the resultant GPC data of PLLA and PDLA for every set of batch experiments are tabulated in Table 1. (Note: A detailed molecular weight description along with PDI of PLLA and PDLA synthesized at different reaction conditions mentioned in the following discussion is given in the Supporting Information (Table S1 and Figure S1-S5). The GPC spectra of PLLA were similar to PDLA so we have shown only PLLA GPC spectra and data in the supplementary information). We have varied monomer to DME concentration (w/w %) from 10 to 30. The polymerization of PLA was carried out at constant parameters like D/L-Lactides ([Monomer]: [Sn(Oct)2]: [1-Dodecanol] as 5000: 1: 1) with 400 bar, 130 °C and 5 hrs. With increasing monomer concentration, the molecular weight of the polymers increased. The polymers molecular weight was highest with M/DME (w/w) 30%. For monomer concentrations of 10 to 20%, polymers with a molecular weight range of Mn ≥ 11,000 to 62,000 gmol-1 are formed (Table 1). The LCST phase behavior of PLA in sc-DME demonstrates the excellent miscibility of the PLA at temperatures below the critical temperature of DME.36,38-41



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Table 1: The effect of various reaction parameters on Lactide polymerization †Conc.

**[M]:[C]:[I]

(w/w)%

Time

T

(hrs)

(oC)

P (bar)

‡PDLA

‡PLLA

3

Mn x 103

Mn x 10

(gmol-1)

(gmol-1)

10

5000:1:1

5

130

400

11

10

20

5000:1:1

5

130

400

56

62

30

5000:1:1

5

130

400

160

167

30

1000:1:1

5

130

400

45

59

30

2000:1:1

5

130

400

91

100

30

3000:1:1

5

130

400

119

120

30

5000:1:1

5

130

400

162

169

30

3000:1:1

3

130

400

72

77

30

3000:1:1

5

130

400

121

124

30

3000:1:1

10

130

400

63

71

30

3000:1:1

24

130

400

32

36

30

3000:1:1

5

120

400

87

90

30

3000:1:1

5

130

400

123

125

30

3000:1:1

5

135

400

154

158

30

3000:1:1

5

140

400

26

29

30

3000:1:1

5

130

300

63

73

30

3000:1:1

5

130

400

124

126

30

3000:1:1

5

130

450

179

184

30

3000:1:1

5

130

500

201

204

† The Monomer to DME concentration. ** [Monomer]: [Catalyst]: [Initiator] ‡ GPC Data

The cloud point pressure was as low as 14 MPa at 393.15K.38 Raising temperature and pressure of the supercritical-polymer fluid system enhances the solubility of the polymers until they meet the cloud point. The phase boundary is shifted towards the bi-phasic condition at cloud point, 10 ACS Paragon Plus Environment

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therefore, the polymer is precipitated. The D/L-Lactide monomers dissolve faster than polymers. At monomer concentration 10%, i.e., with high DME concentration, the solubility of the monomers and hence the low weight polymers are sufficiently high. This situation is far below than the cloud point of the PLA-sc-DME system. Therefore, with higher concentration of scDME at the prescribed reaction conditions, the resulting polymers remained dissolved completely and could not be precipitated. Increasing monomer concentration to 30% could produce polymers with high molecular weight, which could drag the system to meet the cloud point and precipitation at 130 °C and 400 bar. Therefore, the monomer concentration (w/w) 30 % is susceptible to produce high molecular weight homopolymers having Mn ≥ 150,000 gmol-1 in DME-fluid system. To optimize the molecular weight of the homopolymers, we have varied [Monomer]: [Catalyst]: [Initiator] ratios, ([M]: [C]: [I]) from 1000: 1: 1 to 5000: 1: 1 as shown in Table1. We observed a regular trivial increasing trend in molecular weight (Mn) of the PLA with increasing [M]: [C]: [I] as shown in Table 1. Increasing [M]: [C]: [I] ratios from 3000: 1: 1 to 5000: 1: 1, high molecular weight polymers (Mn ≥ 120,000 gmol-1 to160,000 gmol-1 respectively) result as the polymerization progressed. However, the sc-DME-polymer matrix having Mn ≥ 160,000 gmol-1 was found to be quite viscous to flow and pass through the needle valves to stereocomplexation unit for our process. We therefore intentionally selected [M]: [C]: [I] ratio 3000: 1: 1 to generate polymers with optimum molecular weight (Mn ~ 120,000 gmol-1) for our succeeding experiments. We have studied the effect of polymer reaction time on molecular weight from 3 hrs to 24 hrs keeping the other reaction parameters constant such as M/DME w/w 30%, 400 bar, 130 °C and [M]: [C]: [I] as 3000: 1: 1. As evident from Table 1, the molecular weight of homopolymers 11 ACS Paragon Plus Environment


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increased from 3 to 5 hrs of reaction time and decreased afterward. The homopolymers having a molecular weight of Mn ≥ 120,000 gmol-1 were synthesized in 5 hrs of reaction time in sc-DME. With the progress of polymerization, monomers are converted rapidly to high molecular weight polymers. For long hours of polymerization reactions conducted at 130°C, the thermal degradation and side reactions are inevitable. Similarly, we observed a decreasing trend in the molecular weight of PDLA and PLLA at elevated temperature while conducted the temperature studies from 120 to 140 °C as given in Table 1. With increasing temperature from 120 to 130 °C, the polymerization reaction is accelerated so that the PDLA and PLLA got D-Lactyl and LLactyl unit sequences longer enough to give high molecular weight homopolymers. In temperature variation experiment we observed high molecular weight polymers (Mn ≥ 120,000 gmol-1) at 130 °C. The density-solubility correlation seems to be an effective expression when we explain the pressure variation experiments at constant temperature for continuous s-PLA formation. With an increase in pressure from 300 bar to 500 bar, we observed increment in the molecular weight of homopolymers (Mn ≥ 200,000 gmol-1) as infers Table 1. With increasing pressure, the density of the SCF-polymer system increases, which generate long chains of polymers. The sc-DME being an excellent solvent for polylactides provides high molecular weight polymers an efficient solvating power which facilitates their mobility to intact and elongate the polymer chain. After establishing the D/L-Lactide polymerization conducted in sc-DME, we set experiments in stereocomplexation unit. As described before that the dissolved hot polymer solutions from polymerization reactors were shifted manually by opening simultaneously, the high pressure valves to the central stereocomplexation reactor to process further as shown in Figure 1. We investigated the effects of time, temperature, pressure and total homopolymer to DME 12 ACS Paragon Plus Environment

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concentration ratio on the degree of s-PLA while keeping the optimized polymerization conditions as PDLA / PLLA synthesized at 400 bar, 130 °C and 5 hrs with Monomer to DME concentration of 30% w/w. Table 2 compiles the results of experiments conducted for the stereocomplex formation of the PLA. In the time variation experiments in a range of 1.5 to 5 hrs carried out at 250 bar and 70 °C, the degree of s-PLA increased up to ~ 94% provided the reaction conducted for 2 hrs with total homopolymer to DME concentration (w/w) 30% as shown in Table 2. The degree of s-PLA decreased to 46% for long reaction times up to 5 hrs. Increasing reaction time up to 2 hrs provides the polymer chains sufficient mobility to arrange in a good geometric order to commence the s-PLA crystallization. Similarly variation of reaction temperature from 50 to 80 °C gives a maximum degree of s-PLA as 91% at 70 °C when pressure and reaction time were fixed as 250 bar and 2 hrs respectively. Longer reaction times and elevated temperatures promote thermal degradation of polymer chains which lowers the molecular weight of homopolymers ,hence the degree of s-PLA formation decreases. To study the effect of pressure on the degree of s-PLA, we conducted experiments at 70 °C for 2 hrs of reaction time in a pressure range of 150 to 450 bar. We have noticed an increase in degree of s-PLA from 41% at 150 bar to 95% at 350 bar and decreased afterwards as infers Table 2. The sc-DME provides solvation and mobility to polymer chains to be settled to higher orders of geometric dimensions suitable for s-PLA crystal formation and growth. However the degree of s-PLA decreases at very high pressures as shown in Table 2. Free mobility of the homopolymer chains is the key of attaining good geometric dimensions suitable for the racemic crystallization of s-PLA. However, with increasing pressure, the density and viscosity of the Polymer matrix-sc-DME fluid increase. Ultimately the long chains of polymers comprised of



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very high molecular weights face hindrance in movement in this viscous medium of high pressure which eventually decreases the degree of s-PLA.

Table 2: The effect of various reaction parameters on degree of s-PLA ‡Conc.

*∆H1/*∆H2

T

(hrs)

o

( C)

(bar)

( C)

(Jg )

(%)

30

1.5

70

250

167/219

4/49

92

30

2

70

250

168/220

3/47

94

30

3

70

250

169/222

21/51

71

30

5

70

250

164/217

34/29

46

30

2

50

250

169/219

34/17

33

30

2

60

250

167/217

54/49

47

30

2

70

250

172/219

6/57

91

30

2

80

250

169/221

58/23

28

30

2

70

150

171/220

47/34

41

30

2

70

250

174/219

51/17

92

30

2

70

350

176/217

3/60

95

30

2

70

450

171/223

47/25

34

8

2

70

350

169/220

57/6

10

15

2

70

350

170/221

57/43

43

30

2

70

350

175/215

2/59

96

60

2

70

350

173/219

37/29

44

(w/w)%

P

*Tm1/*Tm 2

Time

o

-1

Stereocomplex

‡ The total homopolymers to total DME concentration. *In the DSC Analysis column, superscripts 1 and 2 represent the thermal parameters of the homopolymers and stereocomplexes, respectively.

We also have varied the total homopolymer to DME weight ratio from 8% to 15%, 30% and 60% keeping other reaction parameters fixed as 350 bar, 70 °C and 2 hrs. A maximum degree of 14 ACS Paragon Plus Environment

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s-PLA as ~ 96% is achieved at total homopolymers to DME weight ratio of 30%.

Several

reports have been published regarding the cloud point of polylactide in supercritical fluids. The cloud point pressure has been characterized as a function of temperature, solvent composition and polymer molecular weight.36,38-41 High molecular weight polymers dissolved in sc-DME increase the density of the sc-DME-PLA system. This situation is above the cloud point of scDME-PLA system which eventually turns to be biphasic. Mass transfer with SCF is usually fast. The active viscosities of the SCF are nearly similar to those of the normal gases. In the zone of the critical point, the diffusion coefficient is more than ten times that of a liquid.39-41 Viscosity and diffusivity of SCF are considerably less than liquids at high pressure. However, with dissolved polymers having very high molecular weight, it seems difficult for the mass to flow. The SCF medium is too viscous to give appreciable mobility to polymer chains to produce more ordered state for accelerating s-PLA crystallization.42 Therefore, low degree of s-PLA resulted for these polymers. The optimum reaction conditions for these sets of experiments are s-PLA at 350 bar, 70 °C and 2 hrs keeping the total homopolymers to DME weight ratio as 30% and the PDLA / PLLA polymerization is conducted at 400 bar, 130 °C for 5 hrs with 30% Monomer to DME weight ratio. A comparison of s-PLA nanoparticles with the parent homopolymers (PLLA and PDLA) has been made in Figure 2 (a-c). The s-PLA shows a high melting point of 217 °C as infers Figure 2 (a). The TGA (Figure 2 (b)) shows that thermal degradation of s-PLA has a high onset temperature of 365 °C as shown in Table 3. The degree of stereocomplexation after Hotpress was 52%, which indicates the significant mechanical and thermal tolerance of the s-PLA synthesized by using sc-DME. The stereochemistry and crystal structure of PDLA and PLLA change with sPLA crystal generation. The X-ray diffraction of s-PLA is likely to change the diffraction pattern



from that of its homopolymers.17 The s-PLA formed by sc-DME diffracts the x-ray strongly at 2θ values of 12° with two other relatively weak signals at 20.98° and 24.5° as shown in Figure 2 (c).

Heat Flow (w/g), Exo Up

a

b

100

% Weight

80 60 40

PLLA

PLLA

PDLA

20

s-PLA

s-PLA

PDLA 0 25

75

125

175

Temperature

(oC)

225

50

150

250

Temperature

350

450

(oC)

c s-PLA PLLA

Intensity ( a.u.)

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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PDLA

9

11 13 15 17 19 21 23 25 27

2θ⁰

Figure 2. Comparison of homopolymers with stereocomplex polylactides (a) DSC, (b) TGA, (c) XRD.

The mechanical properties of s-PLA are shown in Table 3. The elongation at break and tensile 16 ACS Paragon Plus Environment

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strength values increased considerably, as compared to the neat homopolymers. Young’s modulus also increased to 1.37 GPa as compared to that of neat homopolymers, which was caused by the high degree of s-PLA. Restricted chain mobility and increased Van der Waals interactions between homopolymer chains alter the morphology of the s-PLA. Increased s-PLA crystalline growth ultimately makes the stereocomplex mechanically strong as compared to the parent homopolymers.43

Table 3: The Thermal and mechanical properties of homopolymers and s-PLA. Material

a

Onset

Elongation at

Tensile

Young’s Modulus

Temperature

break

strength (MPa)

(GPa)

(°C)

(%)

PDLA

315

2.2

12.91

1.25

PLLA

300

1.7

11.2

1.2

s-PLA

365

3.2 a

43.3 a

1.37 a

The degree of stereocomplexation after hot press was 52%.

We were greatly interested in obtaining fine particles of s-PLA for future polymer nanofabrication. We obtained s-PLA particle size ranging from 30 nm to 600 nm, which are in spherical shape as shown in Figure 3 (1-4). Spherical aggregates of 1µm were also observed during SEM analysis as shown in Figure 3 (1). This type of s-PLA aggregates are found useful for accelerated nucleation of biocompatible polymers.44-49 We have used isopropanol as a dispersion medium for s-PLA particle analysis. No surfactant was added to this medium for particle stability as the isopropanol has proven to be a good dispersing medium with enough stability of the particles at room temperature. Further studies are required to get uniform morphology of monodispersed s-PLA nanoparticles. 17 ACS Paragon Plus Environment


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Figure 3. SEM images of stereocomplex polylactide (1, 2) spherical aggregate (3) diversity of 30-40nm s-PLA particles (4) s-PLA powder.


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Conclusions

The polymerization leading to stereocomplexation, an SCF assisted processing proved to be an efficient, economic and feasible strategy of direct polymerization and stereocomplexation of polylactides starting from monomers. We have been successful in synthesizing high molecular weight PDLA and PLLA (Mn ≥ 200,000 gmol-1) in a short time span of 5 hrs in comparison to the days spent in preparing, purifying and drying of polylactides by trivial methods. In our experiments,

the

optimum

conditions

for

PLA

polymerization

leading

to

PLA

stereocomplexation in sc-DME processing were: sc-DME at 130 °C and 400 bar for 5 hrs for polymerization and 70 °C and 350 bar for 2 hrs for stereocomplexation provided the content to DME concentration ratio is fixed at 30 % throughout the process. The supercritical DME is a viable choice for PLA polymerization and stereocomplexation. It serves to be an effective strategy of polymerizing, dissolution and facile shifting of high molecular weight polymers from one reactor to another with remarkable time saving. A very bright aspect of this PLA-sc-DME processing is the formation of a fine s-PLA powder in an excellent yield for future nano-scale polymer fabrication, molding, melt-blending, crystal boosting, thin film preparation and serving as an effective nucleating agent. We obtained a diversity of particle size ranging from 30 nm to 600 nm with spherical shape, including aggregates and solely distributed population of stereocomplex particles. The s-PLA has proven to be mechanically strong with good thermal tolerance in comparison to its parents. We believe that sc-DME can generate particle size of variable range from nanometer to micrometer of polylactide and co-polylactide stereocomplexes with remarkable benefits of commercial and biomedical applications. SEM images confirm that the particles and aggregates of s-PLA particles are spherical in shape. This type of s-PLA aggregates are used to enhance the 19 ACS Paragon Plus Environment


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mechanical properties of enantiopure polylactides. The nanoparticles s-PLA are being applied in biomedical fields for bone and tissue regeneration.

Supporting Information Supplementary Information Data includes page 1-5 with GPC Spectra of PLLA Figure S1-S5 and Table S1: The effec of various reaction parameters on Lactide polymerization.

Acknowledgement This work was supported by a National Research Foundation of Korea grant funded by the Korean Government (MEST) NRF-2010-C1AAA001-2010-0028939.

*Corresponding author 2. Tel: + 82-2-2260-3707 Fax: +82-2-2267-7460. Email: [email protected]

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Table of Contents Graphics only:

A novel strategy of Lactide polymerization leading to stereocomplex polylactide nanoparticles using supercritical fluid technology Gulnaz Bibi

1

1, 2

, Youngmee Jung 2, 3, Jong-Choo Lim 1,*, Soo Hyun Kim 2, 3, 4, **

Department of Chemical and Biochemical Engineering, Dongguk University-Seoul, 3-26 Pil-Dong, Chung-Gu,

Seoul 100-715, Republic of Korea 2

Biomaterials Research Center, Korea Institute of Science and Technology, Seoul 136-791, Korea

3

Korea University of Science and Technology, 113 Gwahangno, Yuseong-gu, Daejeon 305-333, Korea

4

KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, 136-701, Korea

Synopsis: Nanoparticles of stereocomplexed polylactides have been synthesized directly from D/L-Lactide momoners in a semi-continuous process using supercritical dimethyl ether.


Novel Strategy of Lactide Polymerization Leading to Stereocomplex

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