Poly(lactic acid) stereocomplexes: A decade of progress

A highly tunable nanoparticle (NP) system with multifunctionalities was developed as drug nanocarrier via a facile layer-by-layer (LbL) stereocomplex (SC) self-assembly of enantiomeric poly(l-lactic acid) (PLLA) and poly(d-lactic acid) (PDLA) in solution using silica-coated magnetite (Fe3O4@SiO2) as template. The poly(lactide) (PLA) SC coated NPs (Fe3O4@SiO2@-SC) were further endowed with different stimuli-responsiveness by controlling the outermost layer coatings with respective pH-sensitive poly(lactic acid)-poly(2-dimethylaminoethyl methacrylate) (PLA-D) and temperature-sensitive poly(lactic acid)-poly(N-isopropylacrylamide) (PLA-N) diblock copolymers to yield Fe3O4@SiO2@SC-D and Fe3O4@SiO2@SC-N NPs, respectively, while the superparamagnetic properties of Fe3O4 were maintained. TEM images show a clearly resolved core-shell structure with a silica layer and sequential PLA SC co/polymer coating layers in the respective NPs. The well-designed NPs possess a size distribution in a range of 220-270 nm and high magnetization of 70.8-72.1 emu/g [Fe3O4]. More importantly, a drug release study from the as-constructed stimuli-responsive NPs exhibited sustained release profiles and the rates of release can be tuned by variation of external environments. Further cytotoxicity and cell culture studies revealed that PLA SC coated NPs possessed good cell biocompatibility and the doxorubicin (DOX)-loaded NPs showed enhanced drug delivery efficiency toward MCF-7 cancer cells. Together with the strong magnetic sensitivity, the developed hybrid NPs demonstrate a great potential of control over the drug release at a targeted site. The developed coating method can be further optimized to finely tune the nanocarrier size and operating range of pHs and temperatures for in vivo applications.

Poly(lactic acid) (PLA) is a bio-based biodegradable polymer that can be produced from renewable resources including starch from corn and potatoes, sugar from beets and sugar cane, and so forth. The carbon in PLA originates from atmospheric carbon dioxide, which is immobilized in glucose by photosynthesis; therefore, the carbon dioxide formed by its disposal, incineration, or biodegradation does not increase the total amount of atmospheric carbon dioxide. Poly(lactic acid) and its copolymers have attracted significant attention in environmental, biomedical, and pharmaceutical applications and as alternatives to petro-based polymers. Among their applications as alternatives to petro-based polymers, packing applications are the primary one. Most commercially available poly(L-lactic acid) (PLLA) is used for packaging, automobile interiors, electronics chassis and other consumer products. However, some applications require a higher mechanical performance and resistance to hydrolytic/thermal degradation. In addition to composite or fiber-reinforced plastic formation, stereocomplexation between enantiomeric PLLA and poly(D-lactic acid) is a promising method for producing high-performance PLA-based materials because it has been shown to enhance the mechanical performance and resistance to hydrolytic/thermal degradation of PLA-based materials. The physical properties, hydrolytic degradation, and biodegradation of PLA can be controlled by altering, for instance, their molecular and higher ordered structures. This chapter outlines the basic aspects of synthesis, processing, structures, physical properties, degradation and applications of PLA.

Structure evolution of amorphous poly(d-lactic acid) on highly oriented poly(l-lactic acid) film during annealing

New enantiomeric stereo periodical copolymers (SPCPs) of lactic acids, poly(l-lactic acid–l-lactic acid–d-lactic acid) [P(LLA-LLA-DLA)] and poly(d-lactic acid–d-lactic acid–l-lactic acid) [P(DLA-DLA-LLA)] as typical and most simple examples of enantiomeric SPCPs, which cannot be synthesized by catalytic stereoselective polymerization of lactide or lactic acid, were synthesized by preparing the stereosequence-controlled trimers and their polycondensation. A new type of stereocomplex (SC) formation between the synthesized enantiomeric SPCPs was reported for the first time. Unblended P(LLA-LLA-DLA) and P(DLA-DLA-LLA) had two types of crystalline forms, tentatively named α- and β-forms, for solvent evaporation (or purification) and melt-crystallization, respectively. Interestingly, the melting temperature values of SC crystallites of P(LLA-LLA-DLA)/P(DLA-DLA-LLA) blend (143.4–144.0 °C) were between those of α-form (157.6–158.0 °C) and β-form (119.0–119.5 °C) homocrystallites of unblended P(LLA-LLA-DLA) and P(DLA-DLA-LLA), in marked contrast with the results reported for enantiomeric poly(l-lactic acid) and poly(d-lactic acid) homopolymers. The radial growth rate of spherulites (G) of the P(LLA-LLA-DLA)/P(DLA-DLA-LLA) blend with SC crystallites (6.6 × 10–2 μm min–1) at crystallization temperature = 100 °C was much higher than those of unblended P(LLA-LLA-DLA) and P(DLA-DLA-LLA) with β-form homocrystallite spherulites (1.8 × 10-2 and 8.6 × 10-3 μm min-1, respectively). The G values of unblended and blend specimens were 1–4 orders of magnitude lower than those of isotactic and syndiotactic poly(lactic acid)s. The present study strongly suggests the probability of new types of SC formation between enantiomeric SPCPs with a wide variety of stereosequences and is expected to pave the way to widen the physical properties and biodegradation behavior and rate of PLA-based materials by synthesis and stereocomplexation of various types of SPCPs.

Stereocomplex (SC) crystallization between polymer enantiomers has opened a promising avenue for preparing high-performance materials. However, high-crystallinity SCs are difficult to achieve for high-molecular-weight (HMW) enantiomeric blends of chiral polymers [e.g., poly(lactic acid)]. Despite extensive studies, why HMW enantiomeric blends have difficulty in SC crystallization has not been clarified. Herein, we chose the HMW poly(l-lactic acid)/poly(d-lactic acid) (PLLA/PDLA) 1/1 blend as the model system and demonstrated the crucial role of chain entanglement in regulating SC crystallization. PLLA/PDLA blends with various entanglement degrees were prepared by freeze-drying. We observed that disentangling promoted not only the crystallization rate but also the crystallinity of SCs in both the nonisothermal and isothermal processes. The less-entangled samples crystallized exclusively as the high-crystallinity SCs at different temperatures, in contrast to the predominant homocrystallization that occurred in the common entangled samples. This study provides deep insight into the SC crystallization mechanism of polymers and paves the way for future research attempting to prepare SC materials.

Stereocomplex (SC) crystallization has been an effective method to improve the heat resistance of poly(lactic acid) (PLA). However, the preparation of SC-type PLA material is still a challenge because SC crystallization is much less prevailing than homocrystallization in the high-molecular-weight (HMW) poly(l-lactic acid)/poly(d-lactic acid) (PLLA/PDLA) racemic blends. In this study, we have successfully promoted SC formation and controlled crystal morphology of a HMW PLLA/PDLA blend by using a self-assemblable aryl amide nucleator, N,N′,N″-tricyclohexyl-1,3,5-benzenetricarboxylamide (BTCA). Crystallization kinetics, polymorphic crystalline structure, crystal morphology and superstructure of BTCA-nucleated PLLA/PDLA blends were investigated. During the nonisothermal melt crystallization and isothermal crystallization at different temperatures (80–170 °C), the crystallization rate of PLLA/PDLA blend is significantly promoted and the fraction of SCs is enhanced with incorporating small amount of BTCA. SCs a...

Enhanced heat resistance and compression strength of microcellular poly (lactic acid) foam by promoted stereocomplex crystallization with added D-Mannitol

Poly(lactide)s [i.e. poly(lactic acid) (PLA)] and lactide copolymers are biodegradable, compostable, producible from renewable resources, and nontoxic to the human body and the environment. They have been used as biomedical materials for tissue regeneration, matrices for drug delivery systems, and alternatives for commercial polymeric materials to reduce the impact on the environment. Since stereocomplexation or stereocomplex formation between enantiomeric PLA, poly(L-lactide) [i.e. poly(L-lactic acid) (PLLA)] and poly(D-lactide) [i.e. poly(D-lactic acid) (PDLA)] was reported in 1987, numerous studies have been carried out with respect to the formation, structure, properties, degradation, and applications of the PLA stereocomplexes. Stereocomplexation enhances the mechanical properties, the thermal-resistance, and the hydrolysis-resistance of PLA-based materials. These improvements arise from a peculiarly strong interaction between L-lactyl unit sequences and D-lactyl unit sequences, and stereocomplexation opens a new way for the preparation of biomaterials such as hydrogels and particles for drug delivery systems. It was revealed that the crucial parameters affecting stereocomplexation are the mixing ratio and the molecular weight of L-lactyl and D-lactyl unit sequences. On the other hand, PDLA was found to form a stereocomplex with L-configured polypeptides in 2001. This kind of stereocomplexation is called "hetero-stereocomplexation" and differentiated from "homo-stereocomplexation" between L-lactyl and D-lactyl unit sequences. This paper reviews the methods for tracing PLA stereocomplexation, the methods for inducing PLA stereocompelxation, the parameters affecting PLA stereocomplexation, and the structure, properties, degradation, and applications of a variety of stereocomplexed PLA materials.

Poly(l-lactic acid) (L)/poly(d-lactic acid) (D) blends form a stereocomplex (SC) at a mixing ratio of 7/3-3/7. The stoichiometry and packing structure of L/D in the SC are controversial topics because the SC is semicrystalline and because the enantiomeric pair has the same chemical structure. In this study, both the stoichiometry and packing structure of 33% 13C CH3-labeled (l) L/nonlabeled D blends at mixing ratios of 7/3-3/7 were investigated by using solid-state (SS) NMR. The 13C CO signals in natural abundance provided the fractions of the SC (ΦSC), α, and amorphous regions of l-L/D blends. Moreover, the 33% 13CH3-labeled signals could determine the fraction of only l-L in the SC (ΦL) and amorphous region. These two data sets allowed us to determine the stoichiometry of l-L/D in the SC (ΦL-SC/ΦD-SC) to be 1/1. 13C-13C double-quantum (DQ) buildup curves of l-L in the SC followed one universal curve even at different mixing ratios. Comparison of the experimental and simulated DQ curves led to the conclusion that all SC crystals adopt a regular packing structure at varied mixing ratios.

The inexistence of epitaxial relationship between stereocomplex and α crystal of poly(lactic acid): Direct experimental evidence

Stereocomplex crystallization of equimolar Poly(L-lactic acid)/Poly(D-lactic acid) blends from melt with lowered chain entanglements

Stereocomplex- and homo-crystallization behavior, polymorphism, and thermal properties of enantiomeric random copolymers of l- and d-lactic acids from the melt

Stereocomplex (SC) crystallization, homocrystallization, and polymorphism of poly(l-lactic acid-co-l-alanine) [P(LLA-LAL)] and poly(d-lactic acid-co-d-alanine) [P(DLA-DAL)] copolymers with wide alanine unit content ranges from 0 to 21 and 22 mol% are investigated for melt-crystallization. P(LLA-LAL)/P(DLA-DAL) blends crystallize for wide alanine unit content ranges compared to unblended P(LLA-LAL) and P(DLA-DAL) samples, due to facile SC crystallization compared to homocrystallization. The phase diagrams of the unblended samples [α- and δ-form homocrystallites] and the blend samples (SC and homocrystallites) are drawn. The transition crystallization temperature of unblended samples from α-form to δ-form decreases with an increase in alanine unit content. In the unblended and blend samples, alanine units are correspondingly incorporated in α-form homocrystalline regions and excluded from SC crystalline regions. The maximum radial growth rate values of spherulites are higher for the blend samples than for the unblended samples. The experimental crystallization half time [tc(1/2)(exp)] values of the unblended samples increase with an increase in alanine unit content, whereas the tc(1/2)(exp) values of the blend samples with alanine unit contents of 3 and 4 mol% and 6 and 6 mol% and of 12 and 13 mol% are respectively higher than and similar to those of poly(l-lactic acid)/poly(d-lactic acid) blend.

It is critical to broaden the applications of poly(L-lactic acid) foams by improving heat resistance properties. The stereocomplex crystallites that are formed by melt blending of poly(L-lactic acid)/polylactide possess high melting point of about 220℃ and thus exhibit high heat resistance; therefore, the introduction of stereocomplex crystallites tends to improve the thermal stability of poly(lactic acid) foam. Unfortunately, using the solid-state foaming method, it was found that the expansion ratio of the obtained poly(lactic acid) foams was compromised with the value of 1.7 times once the stereocomplex crystallites were formed during the sample saturation stage. In this study, by applying a high compression molding temperature of 230℃, the as-prepared poly(L-lactic acid) and poly(L-lactic acid)/polylactide blends were amorphous. After being CO2 saturated at a mild condition, the specimens were foamed at 90–160℃. The wide-angle X-ray diffraction profiles presented that the stereocomplex crystallites and PLA homocrystals were in-situ generated during the foaming process. It is observed that the in-situ formed stereocomplex crystallites could act as the physical cross-linking agent to stabilize the nucleated bubbles and suppress cell coalescence, resulting in the increased expansion ratio (with value of about 23.6–25.6 times) and cell density, especially at high foaming temperatures and extended foaming time. Furthermore, the in-situ formed stereocomplex crystallites during the foaming increased the heat resistance performance of poly(L-lactic acid) foams. This novel crystallization control method helps us to find a balance point in preparing poly(L-lactic acid) foam with high expansion ratio, well-defined cell structure and high heat resistance performance.

We tried to blend PLLA and PDLA at overall compositions to form PLA stereocomplexes (SC). The presence of the SC crystalline phase in the PLLA matrix was verified by differential scanning calorimetry (DSC). As a result, a various PDLA composition of the PLA SC blends can influence PLA SC formation. And the largest amount of PLA SC crystallites was formed when PLLA/PDLA ratio is 50/50. In addition, we have tried to do PLA SC toughening with two impact modifiers in 92/8, 85/15 ratio of PLLA/PDLA to enhance the mechanical properties such as impact strength. Thermal and mechanical properties of PLA SC were investigated by DSC, HDT, Izod impact tester and UTM. PLA SC formation decreased when 10-20 wt% of Strong120 (impact modifier) was added. On the other hand, there is no effect on PLA SC formation when 10-20% of Elvaloy (impact modifier) was added. HDT values dramatically increased over 100℃ with the addition of PDLA. However, HDT decreased as Strong120 and Elvaloy content increased. Finally, we could find well balanced composition of toughened PLA SC with 10wt% of impact modifier in flexural modulus and impact strength.요 약