Effect of chain segment length on crystallization behaviors of poly( l -lactide-b-ethylene glycol-b- l -lactide) triblock copolymer

Abstract

The poly(l-lactide-b-ethylene glycol-b-l-lactide) (PLLA-PEG-PLLA) triblock copolymers with different chain segment length are fabricated by ring-opening polymerization. The structure, molecular weight, and crystallization behaviors of the triblock copolymers are characterized by Fourier transform infrared, nuclear magnetic resonance spectroscopy, gel permeation in chromatography, X-ray diffraction, differential scanning calorimetry, and polarizing optical microscopy (POM). The results show that the increase of block length is beneficial to improve its crystallization. In addition, the triblock copolymer exhibits a double crystallization phenomenon. The POM results indicate that PEG and PLLA chains of the copolymer crystallize in their respective crystallization temperature regions. The growth rate of the PLLA spherocrystal decreases and the dendritic spherocrystals appear with increasing the PEG chain length when the PLLA chain of the copolymer is isothermal crystallized at 80°C and PLLA chain length is constant. The growth rate of the PEG spherocrystal decreases and the spherocrystal morphology changes little with increasing PLLA chain length when the PEG chain is isothermal crystallized at 25°C and the length of PEG chain remained unchanged.

Keywords

PLLA triblock copolymers crystallization behavior morphology

Introduction

Block copolymers have been combined with two or more chemical structures and have excellent properties. Recently, block copolymers have been widely applied as pressure sensitive adhesives, additives, drug delivery carriers, and smart materials.^1

-5 Polylactide and polyethylene glycol blocks copolymers (PLA-b-PEG) have an important position due to temperature sensitivity, good biocompatibility, and degradability.^6

-11 The strength and toughness of PLA-b-PEG copolymers mainly depend on the semi-crystalline structure. The interplay between PLA and PEG in the crystallization process is very important for the formation of final structure.¹² The crystallization process and crystal morphology of PLA-b-PEG copolymers were investigated.^13
-15 The crystallization behaviors and morphology of copolymers are different by comparing with the mixture of homopolymers.¹⁶ Huang et al.¹⁷ studied the phase separation process of diblock copolymers containing 24% PLA and 14% PEG. The differential scanning calorimetry (DSC) and small-angle X-ray scattering results revealed that the disorder-to-order process is driven by the crystallization of PLA. Sun et al.¹⁸ exhibited the effect of PEG content from 7% to 52% on the crystallization of PLA chain, showing the crystallization rate of PLA is improved. Yang et al.¹⁹ found that the crystallization rate of PEG chain increased when the components of PEG chain are between 50% and 67%. In addition, some scholars^13,16,20 also studied the crystal morphology of PLA-b-PEG by polarizing optical microscopy (POM), and found that the crystal morphology of PLA chain is affected by PEG chain. However, after PLA chain are crystallized, the crystallization process does not affect the crystal structure of the original PLA chain. Due to the presence of two different chains within the PLA and PEG diblock copolymer (PLA-b-PEG), the crystallization between PLA and PEG interacts with each other.

The most of above work focus on the influence of block components on the crystallization and morphology of PLA-b-PEG diblock copolymers. However, only a few studies report the effect of the chain length on the crystallization of copolymers. Yang et al.²¹ studied the effect of PLA chain length on the crystallization behaviors of PEG chain. It is found that the restriction effect of PLA chain on PEG chain is gradually increased when the length of PEG chain remains unchanged. Hu et al.²² found that PLA crystallization is limited when the length of PEG chain does not change and the length of PLA chain increases, which is attributed to the viscosity of the PLA system. Although some studies were reported on the synthesis and properties, the crystallization behaviors and spherocrystal morphologies of poly(l-lactide-b-ethylene glycol-b-l-lactide) (PLLA-PEG-PLLA) triblock copolymers,^8,23 however, the mechanism is still not very clear.

In this work, PLLA-PEG-PLLA triblock copolymers with different chain segment length were synthesized and their structures were analyzed by Fourier transform infrared spectroscopy (FTIR), ¹H-nuclear magnetic resonance (NMR) spectroscopy, and gel permeation chromatography (GPC). The influences of PLLA and PEG chain segment length on the crystallization behaviors and the spherulite morphologies of PLLA-PEG-PLLA triblock copolymers were characterized and discussed in detail using POM, X-ray diffraction (XRD), and DSC. In addition, the crystallization mechanism of PLLA-PEG-PLLA triblock copolymers was also discussed in detail.

Experimental

Materials

l-Lactide (l-LA), analytically pure, was purchased from Guangdong Guanghua Weiye Co., Ltd, China. Terminal bishydroxypolyethylene glycol (the molecular weight is 2000, 4000, 6000 and 8000 g mol⁻¹, respectively), analytical grade, was purchased from Aladdin, China. Toluene, analytical grade, was purchased from Chongqing Chuandong Chemical Co., Ltd, China. Tetrahydrofuran (THF), petroleum ether, diethyl, and stannous octoate, analytical grade, were purchased from Tianjin Fuyu Fine Chemical Co., Ltd, China.

Synthesis of PLLA-PEG-PLLA triblock copolymer

The typical procedure for synthesis of PLLA-PEG-PLLA triblock copolymers was previously reported.²⁴ In polymerization, the fixed ratio of PEG and l-LA ether (the ratio is slightly higher than the theoretical design value) were dissolved in toluene and introduced into a three-neck round bottom flask. Then stannous octoate was added, and the solution was stirred at room temperature for 10 min. After that the flask was placed in an oil bath maintained at 110°C under nitrogen (N₂) atmosphere for 12 h. And then the mixture was cooled to room temperature, and precipitated out white solid in ice ethyl. The white solid was dissolved in dichloromethane, and dropped into ice diethyl ether to precipitate, and suction filtration was repeated three times. The purified product was dried in a vacuum drying.

Characterization and measurements

FTIR spectra were collected using a Thermo Nicolet iS50 FTIR spectrometer (Waltham, MA, USA) in the wavenumber range of 400–4000 cm⁻¹ with KBr pellet.

The chemical structures of the triblock copolymers in CDCl₃ were analyzed by ¹H-NMR (400 MHz Bruker, Germany). The molecular weights and compositions of the triblock copolymers were determined by NMR. The number-average molecular weight (M_n ) and PLLA-PEG-PLLA block ratio were calculated from the integration of ¹H-NMR from the ¹H-NMR spectra obtained in CDCl₃.⁷ Polydispersity was measured against polystyrene standards using GPC (Shimadzu HPLC LC-20A, Japan) with the flow rate of 1 mL min⁻¹ at the room temperature. The column temperature was 35°C, and the THF was a mobile phase.

XRD patterns of the samples were performed using an X-ray diffractometer (X’pertPowder, PANalytical, Netherlands) with a Cu K_α radiation (λ = 0.154 nm) generated at 50 kV and 250 mA. Samples were scanned from 10° to 30° at a scanning rate of 2°C min⁻¹.

DSC measurements were recorded with a DSC 910 of DuPont Instrument (Wilmington, USA) under N₂ atmosphere. The samples were heated from room temperature to 180°C with a heating rate of 10°C min⁻¹, and kept for 5 min to erase any thermal history. Then samples were cooled to −20°C with a cooling rate of 10°C min⁻¹ and then heated to 180°C with a heating rate of 10°C min⁻¹. The melt crystallization temperature (T _mc), crystallization enthalpy (ΔH _mc), melting temperature (T _m), and melting enthalpy (ΔH _m) were obtained. Degrees of crystallinity (X _ci) were calculated from X _ci = ΔH _m,i/ω_iΔH _m,I, where ΔH _m,i is the corresponding melting enthalpy, and ω_i is the weight fraction for the block considered.¹⁶ ΔH _m,i is enthalpy of fusion of the corresponding 100% crystal structure. ΔH _m,i values of 197 and 94 J g⁻¹ were used for PEG and PLLA, respectively.¹⁴

POM (AxioScope.A1, Carl Zeiss, Germany) was used to observe the crystal morphology of spherulites. The samples were melted at 180°C under N₂ gas protection and observed crystal morphology under different heat treatment conditions. Overall crystallization behaviors of samples were also monitored by the digital images.

Results and discussion

Chemical structure and composition of copolymers

Figure 1 shows FTIR spectra of pure PEG, l-LA, and PLLA-PEG-PLLA triblock. It is observed from Figure 1 that the characteristic peak at 1097 cm⁻¹ appears, which is assigned to the C–O– and –OH. The copolymer exhibits a double characteristic peak at 1133 cm⁻¹, which is due to the presence of –CH₃ in the ortho position of C–OH. There is a super-conjugated σ–ρ effect between –CH₃ and O atoms, resulting in a high frequency displacement with the stretching vibration frequency of C–O–. The absorption peak at 1188 cm⁻¹ corresponds to the stretching vibration of C–O– in the ester group of copolymers and the characteristic peak at 1753 cm⁻¹ corresponds to the C=O stretching vibration peak in the ester group, which indicates –COO– in the copolymer. In addition, the absorption peaks at 2977, 2947, and 2878 cm⁻¹ are assigned to stretching vibration of –CH₃, –CH, and CH₂, respectively_. The peak at 453 cm⁻¹ is assigned to bending vibrational peak of –CH₃.⁸

Figure 1.

FTIR spectra of (a) PLLA-PEG-PLLA triblock copolymers, (b) PEG, and (c) l-lactic.

The ¹H-NMR and ¹³C-NMR spectra of PLLA-PEG-PLLA triblock copolymers with different chain length are shown in Figures 2 and 3, respectively. As shown in Figure 2, the peaks at δ = 1.59 and 5.20 ppm are assigned to protons a and b of PLLA, respectively, and the area rate of the peak is about 3:1, which corresponds to the rate of H atoms in the PLLA chain. The peak at δ = 3.6 ppm is attributed to proton c of PEG.²³ Since the excessive PEG is removed by purification treatment, the proton b of PEG will not occur. The peak at δ = 7.36 ppm is assigned the proton peak of the residual solvent. It is observed from Figure 3 that the positions of the respective copolymer peaks are the same. The peaks at δ = 16.88 and 21.5 ppm are assigned to C atoms at proton a and a′ of PLLA chain. The peak at δ = 170.8 ppm is assigned C atoms at proton c of PLLA chain. The characteristic peaks at δ = 70.1and 66.8 ppm are assigned C atoms at proton b and b′ of PEG chain. At δ = 76.36 ppm, it should be the characteristic peak of the test solvent chloroform. All these FTIR and NMR results demonstrate the successful synthesis of PLLA-PEG-PLLA triblock copolymers with controlled PLA block length.

Figure 2.

¹H-NMR spectra of PLLA-PEG-PLLA triblock copolymers.

Figure 3.

¹³C NMR spectra of PLLA-PEG-PLLA triblock copolymers.

Molecular weights of PLLA-PEG-PLLA triblock copolymer are also measured by GPC and calculated from NMR spectrum by comparing NMR peak intensities. The GPC curves of samples are shown in Figure 4 and the corresponding data are listed in Table 1. As can be seen from Figure 4 and Table 1, the triblock copolymer has a very narrow molecular weight distribution, and the lowest molecular weight distribution index is 1.09, which is close to a single distribution. This further proves that the synthesized product is a copolymer rather than a blend of PLLA and PEG.

Figure 4.

GPC curves of PLLA-PEG-PLLA triblock copolymers: (a) LA₄₃ ³EG₅₇ ⁸LA₄₃ ³, (b) LA₄₃ ^2.2EG₅₇ ⁶LA₄₃ ^2.2, (c) LA₃₁ ^0.9EG₆₉ ⁴LA₃₁ ^0.9, (d) LA₄₃ ^1.5EG₅₇ ⁴LA₄₃ ^1.5, (e) LA₆₀ ³EG₄₀ ⁸LA₆₀ ³, and (f) LA₆₀ ^1.5EG₄₀ ²LA₆₀ ^1.5.

Table 1.

Molecular weight of PLLA-PEG-PLLA triblock copolymers.

Samples	EG/LA^a (wt%)	Structure	M_n EG block (g mol⁻¹)	M_n LA block (g mol⁻¹)^b	M_ω /M_n ^c
LA₄₃ ³EG₅₇ ⁸LA₄₃ ³	57/43	3000-8000-3000	8000	3000	1.09
LA₄₃ ^2.2EG₅₇ ⁶LA₄₃ ^2.2	57/43	2200-6000-2200	6000	2200	1.13
LA₃₁ ^0.9EG₆₉ ⁴LA₃₁ ^0.9	69/31	900-4000-900	4000	900	1.09
LA₄₃ ^1.5EG₅₇ ⁴LA₄₃ ^1.5	57/43	1500-4000-1500	4000	1500	1.09
LA₆₀ ³EG₄₀ ⁴LA₆₀ ³	40/60	3000-4000-3000	4000	3000	1.13
LA₆₀ ^1.5EG₄₀ ²LA₆₀ ^1.5	40/60	1500-2000-1500	2000	1500	1.11

PLLA-PEG-PLLA: poly(l-lactide-b-ethylene glycol-b-l-lactide); NMR: nuclear magnetic resonance; gel permeation chromatography.

^aExperimental composition as determined by ¹H-NMR (approximately).

^bCalculated M_n estimated by ¹H-NMR for the LA block knowing the M_n of the EO.

^cPolydispersity index of the block copolymer (determined by GPC).

XRD analysis

The XRD patterns of PLLA-PEG-PLLA copolymers are shown in Figure 5. The crystal of the PEG chain is a monoclinic crystal form, and the 2θ values are 15, 19.1, and 23.2°, corresponding to the plane (110), (120), and (032), respectively.²⁰ For PLLA, it has been proved that the ordinary crystals are pseudo-orthorhombic (α crystal,¹⁷ β crystal,²⁵ and γ crystal).²⁶ In addition, the PLLA chain can also crystallize at low temperature to form α′ crystal, which is converted to α crystal after heating. The 2θ values of the α crystal of PLLA chain are 15, 16.7, 19.1, 21, 22.3, and 27.4°, which corresponds (010), (110/200), (203), (204), (015), and (207), respectively. XRD spectra show the peaks at 2θ values of 16.4, 18.7, 24.5° for α′ crystal. However, as shown in Figure 5, the diffraction peaks mainly appear at 2θ = 16.6, 19.1, and 23.2°, suggesting that the PLLA chain mainly forms α crystal in the triblock copolymer.

Figure 5.

XRD patterns of various PLLA-PEG-PLLA triblock copolymers.

It is found from LA₄₃ ³EG₅₇ ⁸LA₄₃ ³, LA₄₃ ^2.2EG₅₇ ⁶LA₄₃ ^2.2, and LA₄₃ ^1.5EG₅₇ ⁴LA₄₃ ^1.5 that the intensity of the diffraction peak is enhanced with growth of PEG and PLLA chains, indicating that the growth of the chains promotes crystallization of the chain itself. This is consistent with the results of Luo et al.²⁷ The three samples show a dispersion peak at 2θ = 16.6°, which is attributed to the amorphous region in the PLLA chain. Interestingly, the three samples have strong peaks at 2θ = 19.1°, which may be the peak of (203) crystal plane of PLLA chain or (120) crystal plane of PEG chain. It is observed from LA₃₁ ^0.9EG₆₉ ⁴LA₃₁ ^0.9, LA₄₃ ^1.5EG₅₇ ⁴LA₄₃ ^1.5, and LA₆₀ ³EG₄₀ ⁴LA₆₀ that the diffraction peak intensity at 2θ = 23.2° becomes weaker with the PLLA chain increase, indicating the growth of PLLA chain confines crystallization of the PEG chain. While the enhancement of the PLLA crystallization peak at 2θ = 16.6° indicates that the growth of the PLLA chain promotes the crystallization itself. It is seen from LA₄₃ ³EG₅₇ ⁸LA₄₃ ³, LA₆₀ ³EG₄₀ ⁴LA₆₀ ³, LA₄₃ ^1.5EG₅₇ ⁴LA₄₃ ^1.5, and A₆₀ ^1.5EG₄₀ ²LA₆₀ ^1.5 that the growth of PEG chain promotes crystallization itself but confines the crystallization of PLLA chain.

Thermal properties

Thermal properties of PLLA-PEG-PLLA triblock copolymers are investigated by DSC, and the results are shown in Figures 6 and 7. The low temperature peak (T _mc-PEG) and high temperature peak (T _mc-PLLA) are assigned to the crystallization peak of PEG and PLLA, respectively. The crystallization is completed in two steps. Firstly, the chain with higher crystallization temperature crystallizes to form a crystal region with a miscible or partially miscible amorphous region system. Secondly, the chain with lower crystallization temperature crystallizes within the system when the temperature is continuously lowered, and crystallization in the zone or amorphous zone is limited by the microphase separation and other chains, which leads to be restricted at the crystallization of the chains at low temperatures.^28
-30 In the case of EO/LA > 1, both LA₄₃ ^2.2EG₅₇ ⁶LA₄₃ ^2.2 and LA₄₃ ^1.5EG₅₇ ⁴LA₄₃ ^1.5 exhibit only one T _mc-PEG. However, LA₄₃ ³EG₅₇ ⁸LA₄₃ ³ shows two crystallization peaks. The double crystal phenomenon was also observed in other work.^28,31 On the one hand, the increase of PLLA chain length will promote the crystallization of PLLA. On the other hand, since relaxation time is proportional to molecular weight, PEG segmental motion induced the orientation of PLLA decays much more slowly for long chains than short chains, which is beneficial to the formation of PLLA crystal precursor and promotes the crystallization of PLLA.²² Long-chain PEG may produce larger flow fields than short-chain PEG. Therefore, two crystal peaks appear for LA₄₃ ³EG₅₇ ⁸LA₄₃ ³. T _mc value of PEG increases with increasing PEG chain length, indicating that the homogeneous nucleation of PEG chain is easier (as listed in Table 2). In the case of EO/LA < 1, T _mc-PLLA value of LA₆₀ ³EG₄₀ ⁴LA₆₀ ³ is 10.5°C, which is higher than that of LA₆₀ ^1.5EG₄₀ ²LA₆₀ ^1.5. This indicates that the growth of PLLA chain promotes the heterogeneous crystallization itself. Compared to LA₄₃ ³EG₅₇ ⁸LA₄₃ ³ and LA₆₀ ³EG₄₀ ⁴LA₆₀ ³, LA₄₃ ^1.5EG₅₇ ⁴LA₄₃ ^1.5 and LA₆₀ ^1.5EG₄₀ ²LA₆₀ ^1.5, it is found that the growth of PEG chain is beneficial to the crystallization of PEG chain. However, the crystallization of PLLA chain is confined with increasing PEG chain length and vice versa. That is because that the movement of PEG chain is not conducive to the orientation of PLLA chain with increasing PEG chain length. In addition, the crystallization enthalpy of PEG chain is reduced and the peak shape becomes narrower with increasing PLLA chain length when PEG chain length is constant, indicating PLLA chain confines crystallization of PEG chain. For LA₄₃ ^2.2EG₅₇ ⁶LA₄₃ ^2.2 and LA₄₃ ^1.5EG₅₇ ⁴LA₄₃ ^1.5, the crystallization peak appears in XRD patterns, however, there is no crystallization peak in DSC curves. The possible reason is that the rapid cooling is too late to crystalline for PLLA chain.

Figure 6.

DSC heating curves of block copolymers at heating rate of 10°C min⁻¹.

Figure 7.

DSC cooling curves of block copolymers at cooling rate of 10°C min⁻¹.

Table 2.

Thermal parameters of PLLA-PEG-PLLA triblock copolymers.

Samples	T _m-PEG (°C)	ΔH _m-PEG (J g⁻¹)	T _m-PLLA (°C)	ΔH _m-PLLA (J g⁻¹)	T _mc-PEG (°C)	ΔH _mc-PEG (J g⁻¹)	T _mc-PLLA (°C)	ΔH _mc-PLLA (J g⁻¹)
LA₄₃ ³EG₅₇ ⁸LA₄₃ ³	46.4	51.4	112.3	7.7	39.4	51.5	80.6	8.0
LA₄₃ ^2.2EG₅₇ ⁶LA₄₃ ^2.2	45.2	46.9	—	—	27.8	46.9	—	—
LA₃₁ ^0.9EG₆₉ ⁴LA₃₁ ^0.9	41.3	73.8	—	—	27.1	69.2	—	—
LA₄₃ ^1.5EG₅₇ ⁴LA₄₃ ^1.5	42.0	41.4	—	—	26.5	42.5	—	—
LA₆₀ ³EG₄₀ ⁴LA₆₀ ³	32.2	15.8	118.7	15.5	27.7	17.5	96.4	17.7
LA₆₀ ^1.5EG₄₀ ²LA₆₀ ^1.5	—	—	115.2	29.2	—	—	85.9	22.5

PLLA-PEG-PLLA: poly(l-lactide-b-ethylene glycol-b-l-lactide).

In the case of EO/LA > 1, for LA₄₃ ³EG₅₇ ⁸LA₄₃ ³, LA₄₃ ^2.2EG₅₇ ⁶LA₄₃ ^2.2, and LA₄₃ ^1.5EG₅₇ ⁴LA₄₃ ^1.5, the value of ΔH _m-PEG increases when the contents of PLLA and PEG chains are constant and the length of PEG and PLLA chains increases. LA₄₃ ³EG₅₇ ⁸LA₄₃ ³ also shows a melting peak at a high temperature, however, LA₄₃ ^2.2EG₅₇ ⁶LA₄₃ ^2.2, LA₄₃ ^1.5EG₅₇ ⁴LA₄₃ ^1.5, and LA₃₁ ^0.9EG₆₉ ⁶LA₃₁ ^0.9 do not show the melting transition because copolymers PLA chain is too short in the case of EO/LA > 1, indicating that the growth of the chains promotes the crystallization itself. However, in the case of EO/LA < 1, the values of ΔH _m-PLLA of LA₆₀ ³EG₄₀ ⁴LA₆₀ ³ and LA₆₀ ^1.5EG₄₀ ²LA₆₀ ^1.5 become smaller and the crystallinity becomes lower when PLLA chain length increases, as listed in Table 3, which is attributed to a change in the proportion of block. For LA₃₁ ^0.9EG₆₉ ⁴LA₃₁ ^0.9, LA₄₃ ^1.5EG₅₇ ⁴LA₄₃ ^1.5, and LA₆₀ ³EG₄₀ ⁴LA₆₀ ³, the T_m and ΔH_m values of PEG chain gradually become smaller when the length of PEG chain is constant and the length of PLLA chain increases. This indicates that the restriction of PEG chain is enhanced by the growth of PLLA chain. For LA₄₃ ³EG₅₇ ⁸LA₄₃ ³ and LA₆₀ ³EG₄₀ ⁴LA₆₀ ³, the T_m and ΔH_m values increase, however, the T_m and ΔH_m values of PLLA decrease for LA₄₃ ³EG₅₇ ⁸LA₄₃ ³ when length of PLLA chain is constant and the length of PEG chain increases, which reveals that restriction of PLLA is enhanced by growth of PEG chain.

Table 3.

Crystallinity of PLLA-PEG-PLLA triblock copolymers.

Samples	ω_i		X_c,i
Samples	PLA block	PEG block	PLA block	PEG block
LA₄₃ ³EG₅₇ ⁸LA₄₃ ³	0.43	0.57	0.14	0.61
LA₄₃ ^2.2EG₅₇ ⁶LA₄₃ ^2.2	0.43	0.57	—	0.55
LA₃₁ ^0.9EG₆₉ ⁴LA₃₁ ^0.9	0.31	0.69	—	0.54
LA₄₃ ^1.5EG₅₇ ⁴LA₄₃ ^1.5	0.43	0.57	—	0.49
LA₆₀ ³EG₄₀ ⁴LA₆₀ ³	0.60	0.40	0.28	0.20
LA₆₀ ^1.5EG₄₀ ²LA₆₀ ^1.5	0.60	0.40	0.52	—

PLLA-PEG-PLLA: poly(l-lactide-b-ethylene glycol-b-l-lactide).

Crystallization morphologies

POM images of isothermal crystallization of LA₄₃ ^1.5EG₅₇ ⁴LA₄₃ ^1.5 at 70 and 25°C are shown in Figure 8. As can be seen from Figure 8(a), the number of spherulites in the copolymer increases with increasing time, but the growth rate of spherulites is still very slow. This is consistent with the above analysis of XRD and DSC. For LA₄₃ ^1.5EG₅₇ ⁴LA₄₃ ^1.5, although PLLA chain still crystallizes, the crystallization rate is very slow. No crystallization peak of PLLA chain appears on DSC cooling scans at 10°C min⁻¹. PEG chain can form spherulites at 25°C, and the growth rate is faster, however, the spherulitic morphology is incomplete, as shown in Figure 8(b). It is very interesting to observe that the spherulites of PEG chain gradually cover the spherulites of PLLA chain during the process of growth. This indicates that the crystallization of PEG and PLLA chain is carried out separately in different temperature regions, which is consistent with the report of diblock copolymer by Arnal et al.¹²

Figure 8.

POM micrographs after isothermal crystallization of LA₄₃ ^1.5EG₅₇ ⁴LA₄₃ ^1.5 copolymers at different temperatures: (a) 70°C and (b) 25°C.

Figure 9 shows pictures of isothermal crystallization of LA₄₃ ³EG₅₇ ⁸LA₄₃ ³ and LA₆₀ ³EG₄₀ ⁴LA₆₀ ³ at 80°C. Generally, the melting point of PLLA is between 145°C and 190°C, and the melting point of PEG is around 66°C.¹⁶ The PEG chain is still in a state of motion and does not form crystallization at 80°C. According to Hoffman theory,³² the Regime III temperature region of PLLA is confirmed at the range of 70–95°C. In this triblock copolymer, the PEG segment hinders the PLLA crystallization. Therefore, the crystallization of triblock copolymer is very hard compared with a homopolymer. It is seen from Figure 9 that the growth rate of PLLA chain spherulites is reduced from 1.14 to 0.20 μm s⁻¹ with increasing the length of the PEG chain. This is reduced by 5.7 times. The spherulite morphologies show a distinct dendritic bifurcation. This may be because the increase of PEG block length provides more hindrance to the folding of PLLA chains in crystal thereby reducing crystallinity of PLLA, resulting in the spherulite growth rate of PLLA chain decreases and destruction of the spherulite morphology.

Figure 9.

POM and radial growth rate of spherulites for isothermal crystallization of PLLA-PEG-PLLA at 80°C: (a) LA₄₃ ³EG₅₇ ⁸LA₄₃ ³ and (b) LA₆₀ ³EG₄₀ ⁴LA₆₀ ³.

Figure 10 exhibits POM photos and radial growth rate of spherulites of triblock copolymers at 25°C. The samples are rapidly cooled from the melting state and the presence of crystals is not observed in other temperature regions. The spherulitic morphologies of the triblock copolymers are not much different. The growth rate of spherulites of PEG chain for LA₃₁ ^0.9EG₆₉ ⁴LA₃₁ ^0.9 and LA₄₃ ^1.5EG₅₇ ⁴LA₄₃ ^1.5 are 4.39 and 1.41 μm s⁻¹, respectively, which is attributed to PEG chain confined by the frozen PLLA chain. In addition, the growth rate of spherulites increases from 1.14 μm s⁻¹ to 2.46 μm s⁻¹ when the proportion of the chain is constant and the chains grow synchronously for LA₄₃ ^2.2EG₅₇ ⁶LA₄₃ ^2.2. This indicates that the growth of the chains can promote crystallization itself.

Figure 10.

POM and radial growth rate of spherulites for isothermal crystallization of PLLA-PEG-PLLA at 25°C: (a) LA₃₁ ^0.9EG₆₉ ⁴LA₃₁ ^0.9, (b) LA₄₃ ^1.5EG₅₇ ⁴LA₄₃ ^1.5, and (c) LA₄₃ ^2.2EG₅₇ ⁶LA₄₃ ^2.2.

Figure 11 shows POM diagrams of PLLA-PEG-PLLA with different chain segment length. PLLA chain first forms crystals when the sample is cooled from the melting state. PLLA forms spherulites that are a template of morphology of the block copolymer because the second block that crystallizes at lower temperature (i.e. PEG) is forced to crystallize in the interlamellar and/or interfibrillar regions.¹² It has been concluded from DSC curves that LA₄₃ ³EG₅₇ ⁸LA₄₃ ³ and LA₆₀ ³EG₄₀ ⁴LA₆₀ ³ show double crystallization, however, LA₄₃ ^2.2EG₅₇ ⁶LA₄₃ ², LA₃₁ ^0.9EG₆₉ ⁴LA₃₁ ^0.9, LA₄₃ ^1.5EG₅₇ ⁴LA₄₃ ^1.5, and LA₆₀ ^1.5EG₄₀ ²LA₆₀ ^1.5 show single-chain crystallization. As shown in Figure 11(a) and (c), the spherulites of LA₄₃ ³EG₅₇ ⁸LA₄₃ ³ and LA₆₀ ³EG₄₀ ⁴LA₆₀ ³ have no obvious cross-extinction phenomenon due to the formation of spherulites of PEG chains in the crystal region of PLLA. Therefore, the spherulite morphology is destroyed. POM images of LA₄₃ ^2.2EG₅₇ ⁶LA₄₃ ², LA₃₁ ^0.9EG₆₉ ⁴LA₃₁ ^0.9, and LA₄₃ ^1.5EG₅₇ ⁴LA₄₃ ^1.5 present obvious spheroid morphologies of cross-extinction, indicating that the influence of PLLA on the spherulite morphology is very small below a certain threshold molecular weight. The spherulite morphology of LA₆₀ ^1.5EG₄₀ ²LA₆₀ ^1.5 is destructed to some extent, which shows that the moving PEG chain destroys the spherulite structure of PLLA. In addition, it can be found from Figure 11(c) and (d) that the number of spherulites gradually increases in the field of view. That is because that the rigid PLLA chain promotes nucleation of PEG spherulites as PLLA chain grows.

Figure 11.

POM micrographs of cooling to 25°C at 5°C min⁻¹ for block copolymers after melting for 5 min different triblock copolymers at 25°C: (a) LA₄₃ ³EG₅₇ ⁸LA₄₃ ³, (b) LA₄₃ ^2.2EG₅₇ ⁶LA₄₃ ², (c) LA₃₁ ^0.9EG₆₉ ⁴LA₃₁ ^0.9, (d) LA₄₃ ^1.5EG₅₇ ⁴LA₄₃ ^1.5, (e) LA₆₀ ³EG₄₀ ⁴LA₆₀ ³, and (f) LA₆₀ ^1.5EG₄₀ ²LA₆₀ ^1.5.

Crystallization mechanism of PLLA-PEG-PLLA triblock copolymer

The crystallization mechanism diagram of PLLA-PEG-PLLA triblock copolymer is exhibited in Figure 12. The PLLA and PEG chains are in a free motion state when the triblock copolymer is heated to 180°C. The PLLA chain is folded and crystallized when the temperature is in the crystallization zone of PLLA chain, while the free-moving PEG chain may have two effects on PLLA chain: (1) plasticization and (2) limitation. In the diblock copolymers, plasticization makes PLLA chain easier to fold into spherulites and increases the crystallization rate of PLLA chain.^18,19 However, the results show that the increase of block length of PEG provides more hindrance to the folding of PLLA chains in crystal thereby reducing crystallinity of PLLA in this work. As shown in Figure 12(a), the increase of block length of PEG makes PLLA block more crowded with PEG block, which limits the crystallization of PLLA and destroys the spherulite morphology of PLLA. For example, the spherulite growth rate and crystallinity of LA₆₀ ³EG₄₀ ⁴LA₆₀ ³ are 1.14 and 0.28 μm s⁻¹, respectively, which is higher than that of LA₄₃ ³EG₅₇ ⁸LA₄₃ ³. The spherulite morphology of LA₆₀ ³EG₄₀ ⁴LA₆₀ ³ is also more complete than that of LA₄₃ ³EG₅₇ ⁸LA₄₃ ³. PEG chain is in metastable state and can be folded to form crystals when the temperature reduces to the crystallization region of PEG, however, PLLA chain is in stable state, which can build a stable space around PEG chain. As shown in Figure 12(b), PEG crystallizes inside of the PLLA crystallization. The orientation and crystallization of PEG chain is confined by PLLA chain when the metastable PEG chain begins to fold and form crystallization. For example, for LA₃₁ ^0.9EG₆₉ ⁴LA₃₁ ^0.9 and LA₄₃ ^1.5EG₅₇ ⁴LA₄₃ ^1.5, the spherulite growth rate of PEG is 4.39 and 1.41 μm s⁻¹, and the crystallinity is 0.54 and 0.49, respectively, as PLLA chain grows.

Figure 12.

Diagram of crystallization mechanism of PLLA-PEG-PLLA triblock copolymers.

Conclusions

In this article, the effect of composition and length of chain segment on the crystallization behaviors and morphologies of PLLA-PEG-PLLA is evaluated by XRD, DSC, and POM, and the crystallization mechanism of the triblock copolymer is proposed from the perspective of the interaction between the chains. The molecular weight of PEG ranges from 2 kg mol⁻¹ to 8 kg mol⁻¹ and its content in the synthesized copolymers varies are 40, 57, 69%. The molecular weight of PLLA block ranges from 0.9 kg mol⁻¹ to 3 kg mol⁻¹, and its content in the synthesized copolymers varies are 31, 43, and 60%. The XRD and DSC results show that the growth of PLLA (PEG) chain promotes its own nucleation crystallization and the restriction on the crystallization of PEG (PLLA) chain. The triblock copolymer exhibits a double crystallization phenomenon when the length of PLLA (PEG) chain is kept constant, and the length of PEG (PLLA) chain increases. Isothermal crystallization of LA₄₃ ^1.5EG₅₇ ⁴LA₄₃ ^1.5 indicates that the PLLA and PEG blocks crystallize in different temperature regions. Keeping PLLA (PEG) chain unchanged, the growth of PEG (PLLA) chain reduces, however, the spherical growth rate of PLLA (PEG) chain increases. The non-isothermal crystallization of POM exhibits that the spherulite morphology of the varies copolymers is severely damaged when copolymers exhibit double crystallization, however, the destruction is not significant when copolymers exhibit single crystallization. PLLA chain has a nucleating effect on the formation of spherulites of PEG chain when PEG chain grows.

Footnotes

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was financially supported by the Natural Science Foundation of China (51663006), International Science and Technology Cooperation Project of Sichuan (2019YFH0047), Guizhou Province Graduate Research Foundation (KYJJ2017012), Opening Project of State Key Laboratory of Polymer Materials Engineering (Sichuan University) (2017-4-02), Guizhou Province Science and Technology Program Project ([2017]5788, [2017]5630, [2017]1091), and Guizhou Province Key Topic of Education Teaching Reform for Postgraduates (JGKT2017011).

References

Hami

Amini

Ghazi-Khansari

, et al. Synthesis and in vitro evaluation of a pH-sensitive PLA–PEG–folate based polymeric micelle for controlled delivery of docetaxel. Colloid Surf B 2014; 116: 309–317.

Koutsiouki

Angelopoulou

Ioannou

, et al. TAT peptide-conjugated magnetic PLA-PEG nanocapsules for the targeted delivery of paclitaxel: in vitro and cell studies. Aaps Pharmscitech 2016; 18: 1–13.

Topp

MDC

Dijkstra

Talsma

, et al. Thermosensitive micelle-forming block copolymers of poly(ethylene glycol) and poly(N-isopropylacrylamide). Macromolecules 2016; 30: 8518–8520.

. Polylactide (PLA)-based amphiphilic block copolymers: synthesis, self-assembly, and biomedical applications. Soft Matter 2011; 7: 5096–5108.

Danafar

Rostamizadeh

Davaran

, et al. Drug-conjugated PLA-PEG-PLA copolymers: a novel approach for controlled delivery of hydrophilic drugs by micelle formation. Pharm Dev Technol 2016, 22: 947–957.

Mao

Pan

Shan

, et al. In situ formation and gelation mechanism of thermoresponsive stereocomplexed hydrogels upon mixing diblock and triblock poly(lactic acid)/poly(ethylene glycol) copolymers. J Phys Chem B 2015; 119: 6471–6480.

Abebe

Fujiwara

. Controlled thermoresponsive hydrogels by stereocomplexed PLA-PEG-PLA prepared via hybrid micelles of pre-mixed copolymers with different PEG lengths. Biomacromolecules 2012; 13: 1828–1836.

Massadeh

Alaamery

Alqatanani

, et al. Synthesis of protein-coated biocompatible methotrexate-loaded PLA-PEG-PLA nanoparticles for breast cancer treatment. Nano Rev 2016; 7: 2–6.

Xiong

, et al. A functional iron oxide nanoparticles modified with PLA-PEG-DG as tumor-targeted MRI contrast agent. Pharm Res 2017; 34: 1–10.

10.

Kruse

Greuel

Kreimendahl

, et al. Electro-spun PLA-PEG-yarns for tissue engineering applications. Biomed Tech 2018; 63: 231–243.

11.

Cui

Shao

Wang

, et al. PLA-PEG-PLA and its electroactive tetraaniline copolymer as multi-interactive injectable hydrogels for tissue engineering. Biomacromolecules 2013; 14: 1904–1912.

12.

Arnal

Boissé

Müller

, et al. Interplay between poly(ethylene oxide) and poly(l-lactide) blocks during diblock copolymer crystallization. Crystengcomm 2016; 18: 3635–3649.

13.

Huang

Jiang

, et al. Crystallization and morphology of poly(ethylene oxide-b-lactide) crystalline–crystalline diblock copolymers. J Polym Sci Part B Polym Phys 2010; 46: 1400–1411.

14.

Topolkaraev

, et al. Crystallization and phase separation in blends of high stereoregular poly(lactide) with poly(ethylene glycol). Polymer 2003; 44: 5681–5689.

15.

Yang

Zhao

Zhou

, et al. Single crystals of the poly(l-lactide) block and the poly(ethylene glycol) block in poly(l-lactide)-poly(ethylene glycol) diblock copolymer. Macromolecules 2007; 40: 2791–2797.

16.

Shin

Aamer

, et al. A morphological study of a semicrystalline poly(l-lactic acid-b-ethylene oxide-b-l-lactic acid) triblock copolymer. Macromolecules 2005; 38: 104–109.

17.

Huang

Jiang

, et al. Morphologies and structures in poly(l-lactide-b-ethylene oxide) copolymers determined by crystallization, microphase separation, and vitrification. Polym Bull 2011; 67: 885–902.

18.

Sun

Hong

Yang

, et al. Study on crystalline morphology of poly(l-lactide)-poly(ethylene glycol) diblock copolymer. Polymer 2004; 45: 5969–5977.

19.

Yang

Zhao

Liu

, et al. Isothermal crystallization behavior of the poly(l-lactide) block in poly(l-lactide)-poly(ethylene glycol) diblock copolymers: influence of the PEG block as a diluted solvent. Polym J 2006; 38: 1251–1257.

20.

Chen

Wang

Dong

. Synthesis, characterization, effect of architecture on crystallization, and spherulitic growth of poly(l-lactide)-b-poly(ethylene oxide) copolymers with different branch arms. J Polym Sci Part A Polym Chem 2006; 44: 2034–2044.

21.

Yang

Zhao

Cui

, et al. Nonisothermal crystallization behavior of the poly(ethylene glycol) block in poly(l-lactide)–poly(ethylene glycol) diblock copolymers: effect of the poly(l-lactide) block length. J Polym Sci Part B Polym Phys 2006; 44: 3215–3226.

22.

Zhong

, et al. Shear induced crystallization of poly(l-lactide) and poly(ethylene glycol) (PLLA-PEG-PLLA) copolymers with different block length. J Polym Res 2011; 18: 675–680.

23.

Hoang

Lim

Sim

, et al. Characterization of a triblock copolymer, poly(ethylene glycol)-polylactide-poly(ethylene glycol), with different structures for anticancer drug delivery applications. Polym Bull 2016; 74: 1–15.

24.

Vert

. Synthesis, characterization, and stereocomplex-induced gelation of block copolymers prepared by ring-opening polymerization of l(d)-lactide in the presence of poly(ethylene glycol). Macromolecules 2003; 36: 8008–8014.

25.

Puiggali

Ikada

Tsuji

, et al. The frustrated structure of poly(l-lactide). Polymer 2000; 41: 8921–8930.

26.

Cartier

Okihara

Ikada

, et al. Epitaxial crystallization and crystalline polymorphism of polylactides. Polymer 2000; 41: 8909–8919.

27.

Luo

Bei

, et al. Synthesis and characterization of poly(l-lactide)-poly(ethylene glycol) multiblock copolymers. J Appl Polym Sci 2002; 84: 1729–1736.

28.

Yang

Liang

Luo

, et al. Multilength scale studies of the confined crystallization in poly(l-lactide)-block-poly(ethylene glycol) copolymer. Macromolecules 2012; 45: 4254–4261.

29.

Verónica Castillo

Müller

Raquez

, et al. Crystallization kinetics and morphology of biodegradable double crystalline PLLA-b-PCL diblock copolymers. Macromolecules 2010; 43: 4149–4160.

30.

Huang

Dong

Wang

, et al. Reversible lamellar periodic structures induced by sequential crystallization/melting in PBS-co-PCL multiblock copolymer. Macromolecules 2018; 51: 1100–1109.

31.

Zhou

Sun

Shao

, et al. Unusual crystallization and melting behavior induced by microphase separation in MPEG-b-PLLA diblock copolymer. Polymer 2015; 80: 123–129.

32.

Lorenzo

. Determination of spherulite growth rates of poly(l-lactic acid) using combined isothermal and non-isothermal procedures. Polymer 2001; 42: 9441–9446.