Stereocomplexes of Triblock Poly(lactide- PEG2000-lactide) as Carrier of Drugs

Triblock copolymers of poly(lactide)-poly(ethylene-glycol)-poly(lactide) (PLA-PEG₂₀₀₀-PLA) were synthesized by ring-opening polymerization of lactide and PEG₂₀₀₀ diol as co-catalyst. Stereocomplexes with particle sizes ranging from nanometers to microns were obtained by mixing acetonitrile solutions of pairs of enantiomeric homopoly(lactide) and the triblock copolymers. The stereocomplexes exhibited higher crystalline melting temperatures than the optically pure polymers. The ratio of PLA terminals in the copolymers had a significant effect on their stereocomplex degradation and drug release. These stereocomplexes were used for the encapsulation of dexamethasone for controlled release applications. Dexamethasone phosphate loading capacity, in vitro release, degradation and stability of polymers and formulation were investigated for one month. An increase in the dexamethsone phosphate content in the stereocomplex or a decrease in the PLA ratio in the copolymer resulted in a faster release of drug and polymer degradation.     

Effect of Star-shaped chain architectures on the polylactide stereocomplex crystallization behaviors

Linear and star-shaped polylactides (PLA) with similar molecular weights of each arm are synthesized via ring-opening polymerization of LA with 3-butyn-l-ol and pentaerythritol as initiators,respectively.By solution blending of equivalent mass of poly(L-lactic acid)s (PLLAs) and poly(D-lactic acid)s (PDLAs),perfect PLA stereocomplexes (scPLAs) are prepared and confirmed by WAXD and FTIR analysis.Effect of chain architectures on stereocomplex crystallization is investigated by studying the non-isothermal and isothermal crystallization of linear and star-shaped polylactide stereocomplexes.In dynamic DSC and POM test,star-shaped PLLA (4sPLLA)/PDLA and PLLA/star-shaped PDLA (4sPDLA) stereocomplexes reach rapid crystallization and higher crystallinity due to larger spherulite density of star-shaped chain and excellent chain mobility of linear chain.In isothermal crystallization test,much faster crystallization and less crystallization half-time is obtained with the increase of star-shaped chain.Meanwhile,4sPLLA/PDLA and PLLA/4sPDLA are found to have the highest crystallinity,suggesting limitation of too much star-shaped chain for 4sPLLA/4sPDLA and restriction of linear chain in nucleation capacity for PLLA/PDLA.The results reveal that star-shaped chain has an important influence on the crystallization of scPLAs.     

Effect of blending ratio and oligomer structure on the thermal transitions of stereocomplexes consisting of a D‐lactic acid oligomer and poly(L‐lactide)

Poly(lactic acid) (PLA) stereocomplexes have high potential as renewable materials for advanced polymer applications, mainly due to their high melting temperature (T_m, typically 230–240°C). The properties of PLA stereocomplexes consisting of linear high molar mass homopolymers have been studied extensively in the past, but the available information about the possibilities to affect the thermal properties of the stereocomplex by varying the structure of the blend components has not been sufficient. Novel stereocomplexes containing linear or star‐shaped D ‐lactic acid (D ‐LA) oligomers and high molar mass poly(L ‐lactide) (L‐ PLA) were thus prepared. The T_m and melting enthalpy (ΔH_m) of the racemic crystallites were found to depend strongly on both the blending ratio and the arm‐length of the D ‐lactic acid oligomer. The preparation method of the oligomers, i.e. step‐growth polymerization or ring‐opening polymerization (ROP), did not affect the T_m or ΔH_m of the blends significantly. Slightly higher ΔH_m values were, however, obtained, when linear oligomers were used. The results thus indicated that the T_m and ΔH_m of PLA stereocomplexes could be optimized, simply by selecting a D ‐LA oligomer having a suitable arm‐length and structure as the other blend component. The possibility to adjust the melting behavior of the stereocomplex blend is a significant advantage and could make PLA suitable for a wider range of products used at elevated temperatures. Copyright © 2010 John Wiley & Sons, Ltd.     

Poly(lactide) stereocomplexes: formation, structure, properties, degradation, and applications

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.     

An AFM Study of Poly(L-lactic acid) and Poly(D-lactic acid) Macromolecules and Their Stereocomplexes at the Solid-Air Interface

The self assembly of PLA enantiomers have been studied at the nanometer scale using atomic force microscopy. At first, the conformation of D and L PLA macromolecules in dilute regime and the initial state of aggregation of both enantiomers were successively observed and compared with the aggregation of PLLA/PDLA blends. Our results points out differences in the aggregates structure between the homo-aggregates of each enantiomers and the 3 Dimensional stereocomplexes formed with racemic mixture of D and L entities. On the one hand, D or L PLA chains, which adopt a rigid conformation in dilute regime, form gradually aggregates that tend to grow from a nucleation center. On the other hand, stereocomplexes have a non-compact structure and are elongated with height variations within the fibrils that support the side by side aggregation of D and L helical structures to form thicker fibrils.     

Crystallization and stereocomplexation behavior of poly(D‐ and L‐lactide)‐b‐poly(N,N‐dimethylamino‐2‐ethyl methacrylate) block copolymers

The thermal properties, crystallization, and morphology of amphiphilic poly(D ‐lactide)‐b‐poly(N,N‐dimethylamino‐2‐ethyl methacrylate) (PDLA‐b‐PDMAEMA) and poly (L ‐lactide)‐b‐poly(N,N‐dimethylamino‐2‐ethyl methacrylate) (PLLA‐b‐PDMAEMA) copolymers were studied and compared to those of the corresponding poly(lactide) homopolymers. Additionally, stereocomplexation of these copolymers was studied. The crystallization kinetics of the PLA blocks was retarded by the presence of the PDMAEMA block. The studied copolymers were found to be miscible in the melt and the glassy state. The Avrami theory was able to predict the entire crystallization range of the PLA isothermal overall crystallization. The melting points of PLDA/PLLA and PLA/PLA‐b‐PDMAEMA stereocomplexes were higher than those formed by copolymer mixtures. This indicates that the PDMAEMA block is influencing the stability of the stereocomplex structures. For the low molecular weight samples, the stereocomplexes particles exhibited a conventional disk‐shape structure and, for high molecular weight samples, the particles displayed unusual star‐like shape morphology. © 2011 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 49: 1397–1409, 2011     

Miktoarm star‐shaped poly(lactic acid) copolymer: Synthesis and stereocomplex crystallization behavior

The miktoarm star‐shaped poly(lactic acid) (PLA) copolymer, (PLLA)₂‐core‐(PDLA)₂, was synthesized via stepwise ring‐opening polymerization of lactide with dibromoneopentyl glycol as the starting material. ¹H NMR and FTIR spectroscopy proved the feasibility of synthetic route and the successful preparation of star‐shaped PLA copolymers. The results of FTIR spectroscopy and XRD showed that the stereocomplex structure of the copolymer could be more perfect after solvent dissolution treatment. Effect of chain architectures on crystallization was investigated by studying the nonisothermal and isothermal crystallization of the miktoarm star‐shaped PLA copolymer and other stereocomplexes. Nonisothermal differential scanning calorimetry and polarizing optical microscopy tests indicated that (PLLA)₂‐core‐(PDLA)₂ exhibited the fastest formation of a stereocomplex in a dynamic test due to its special structure. In isothermal crystallization tests, the copolymer exhibited the fast crystal growth rate and the most perfect crystal morphology. The results reveal that the unique molecular structure has an important influence on the crystallization of the miktoarm star‐shaped PLA copolymer. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019 , 57, 814–826     

Crystallization and stereocomplexation governed self‐assembling of poly(lactide)‐b‐poly(ethylene glycol) to mesoscale structures

The stereocomplex formation between enantioselective poly(lactide) (PLA) homopolymers is well understood. In this report an attempt is made to analyze the influence on the self‐assembling of the stereocomplex of enantiomorphic PLA‐PEG di‐ and tri‐blocks in different solvents. Powder diffraction studies showed the poly(ethylene glycol) (PEG) and the PLA blocks crystallize separately forming unique supra structures like rods, discs and coiled coils with dimensions in the micrometer scale in length and sub‐micrometer scale in diameter. The influence of the solvents on the crystal formation was shown in the formation of uniform structures. Discs emerged from equimolar mixtures of the D ‐ and L ‐configured di‐ and tri‐block copolymers, in dioxan and acetonitrile and in water the stereocomplexes crystallized mainly as rods. In some cases the rods were observed as coiled coils. The shape, the hydrophobic/hydrophilic content and the PEG coated surface of the discs give them a future potential as matrix for the controlled and targeted delivery of bioactive agents. Copyright © 2005 John Wiley & Sons, Ltd.     

Linear and four‐armed poly(l‐lactide)‐block‐poly(d‐lactide) copolymers and their stereocomplexation with poly(lactide)s

Linear and four‐armed poly(l ‐lactide)‐block‐poly(d ‐lactide) (PLLA‐b‐PDLA) block copolymers are synthesized by ring‐opening polymerization of d ‐lactide on the end hydroxyl of linear and four‐armed PLLA prepolymers. DSC results indicate that the melting temperature and melting enthalpies of poly (lactide) stereocomplex in the copolymers are obviously lower than corresponding linear and four‐armed PLLA/PDLA blends. Compared with the four‐armed PLLA‐b‐PDLA copolymer, the similar linear PLLA‐b‐PDLA shows higher melting temperature (212.3 °C) and larger melting enthalpy (70.6 J g^?1). After these copolymers blend with additional neat PLAs, DSC, and WAXD results show that the stereocomplex formation between free PLA molecular chain and enantiomeric PLA block is the major stereocomplex formation. In the linear copolymer/linear PLA blends, the stereocomplex crystallites (sc) as well as homochiral crystallites (hc) form in the copolymer/PLA cast films. However, in the four‐armed copolymer/linear PLA blends, both sc and hc develop in the four‐armed PLLA‐b‐PDLA/PDLA specimen, which means that the stereocomplexation mainly forms between free PDLA molecule and the inside PLLA block, and the outside PDLA block could form some microcrystallites. Although the melting enthalpies of stereocomplexes in the blends are smaller than that of neat copolymers, only two‐thirds of the molecular chains participate in the stereocomplex formation, and the crystallization efficiency strengthens. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2014 , 52, 1560–1567     

Poly Lactic Acid (PLA) Nanocomposites: Effect of Inorganic Nanoparticles Reinforcement on Its Performance and Food Packaging Applications

Poly lactic acid (PLA) is a compostable, as well as recyclable, sustainable, versatile and environmentally friendly alternative, because the monomer of PLA-lactide (LA) is extracted from natural sources. PLA’s techno-functional properties are fairly similar to fossil-based polymers; however, in pristine state, its brittleness and delicacy during processing pose challenges to its potential exploitation in diverse food packaging applications. PLA is, therefore, re-engineered to improve its thermal, rheological, barrier and mechanical properties through nanoparticle (NP) reinforcement. This review summarises the studies on PLA-based nanocomposites (PLA NCs) developed by reinforcing inorganic metal/metallic oxide, graphite and silica-based nanoparticles (NPs) that exhibit remarkable improvement in terms of storage modulus, tensile strength, crystallinity, glass transition temperature (Tg) value, antimicrobial property and a decrease in water vapour and oxygen permeability when compared with the pristine PLA films. This review has also discussed the regulations around the use of metal oxide-based NPs in food packaging, PLA NC biodegradability and their applications in food systems. The industrial acceptance of NCs shows highly promising perspectives for the replacement of traditional petrochemical-based polymers currently being used for food packaging.     

Poly(lactic acid)/coplasticized thermoplastic starch blend: Effect of plasticizer migration on rheological and mechanical properties

Polylactic acid (PLA) and thermoplastic starch (TPS) are known as bio‐based and biodegradable thermoplastic polymers that can be used in different applications owing to their inherent physical and mechanical properties. In order to reduce the higher costs of PLA and tuning its physical and mechanical properties suitable for short life packaging applications, blending of PLA with the TPS, more economical biodegradable polymer, has been considered in academic and industrial researches. However, melt blending of PLA with TPS without compatibilization process caused some drawbacks such as coarsening morphology and declining mechanical properties and ductility because of thermodynamic immiscibility, which may restrict its usage in packaging applications. Subsequently, our approach in this research is compatibilization of PLA/TPS blends by utilization of primary well tuning of TPS formulation with a combination of sorbitol and glycerol plasticizers. In this work, the wide composition range of melt mixed PLA/TPS blends was prepared using a laboratory twin screw extruder. The effects of microstructure on the rheological and mechanical properties of PLA/TPS blends were studied using different methods such as scanning electron microscopy (SEM) images, contact angle, oscillatory shear rheological measurements, and tensile and impact strength mechanical tests. The rheological and mechanical properties were interpreted according to the morphological features and considering the possibility of plasticizer migration from TPS to PLA phase during melt blending. Reduction in complex viscosity and storage modulus of PLA matrix samples indicates the improved melt processability of blends. Finally, in comparison with mechanical results reported in literature, our simple approach yielded the blends with elastic modulus and ductility comparable with those of chemically compatibilized PLA/TPS blends.     

Toughening of poly(lactide acid) with low crystallinity through biaxial poststretching

Poly(lactide acid) (PLA) is an eco-friendly, biocompatible and biodegradable polymer that has been extensively explored in diverse applications ranging from biomedical devices to food packages. One well-known limitation of PLA in the applications is its low mechanical toughness and small stretchability. In this work, we have conducted systematic studies of the effects of the thermo-mechanical processing on the mechanical behaviors of PLA with extremely low crystallinity (less than 3%). It is found that a freshly quenched PLA after hot pressing can be quite stretchable and tough. However, after only 2 days of aging at room temperature, the PLA becomes very brittle. We attribute such aging-induced ductile-to-brittle transition of the PLA to its plastic deformation mode changing from shearing to crazing. To increase the toughness and stability of the PLA, we apply poststretching onto the PLA. Our results have shown that after poststretching, both the toughness and stretchability of aged PLA can be greatly increased. Moreover, the mechanical properties of the PLA after poststretching become more aging resistant.     

Nano‐Stereocomplexation of Polylactide (PLA) Spheres by Spray Droplet Atomization

A direct, efficient, and scalable method to prepare stereocomplexed polylactide (PLA)‐based nanoparticles (NPs) is achieved. By an appropriate combination of fabrication parameters, NPs with controlled shape and crystalline morphology are obtained and even pure PLA stereocomplexes (PLASC) are successfully prepared using the spray‐drying technology. The formed particles of varying d ‐ and l ‐LA content have an average size of ≈400 nm, where the smallest size is obtained for PLA50, which has an equimolar composition of PLLA and PDLA in solution. Raman spectra of the particles show the typical shifts for PLASC in PLA50, and thermal analysis indicates the presence of pure stereocomplexation, with only one melting peak at 226 °C. Topographic images of the particles exhibit a single phase with different surface roughness in correlation with the thermal analysis. A high yield of spherically shaped particles is obtained. The results clearly provide a proficient method for achieving PLASC NPs that are expected to function as renewable materials in PLA‐based nanocomposites and potentially as more stable drug delivery carriers.

     

Difference in Glass Transition Behavior Between Semi Crystalline and Amorphous poly(lactic acid) Thin Films

Summary: Semi crystalline and amorphous poly(lactic acid) (PLA) thin films exhibit different glass transition temperature and behaviour, as revealed by ellipsometry. For semi-crystalline poly(L-lactic acid) (PLLA) thin film (with crystalline content between 40 and 60%), the glass transition temperature (T_g) is found to decrease below a film thickness of 50 nm. This depression was interpreted in term of disentenglement effect which is likely to occur upon confining the amorphous PLA phase near a non interacting surface. New results performed on non completed films, i.e. isolated objects, also reveal the lower transition temperature, thus underlying the importance of the entanglement state of the polymer chains on their mobility. For amorphous PLA thin film, obtained from the L and D copolymer, two distinct glass transitions were observed, with the highest Tg attributed to the presence of some nano-phase domains, formed by a possible cooperation of the D and L blocks to form stereocomplexes sequences, within the film. Furthermore, if these T_g remained constant as film thicknesses decrease down to 50 nm, they were also found to slightly decrease for isolated objects, thus supporting the importance of the entanglement hypothesis on the glass transition.     

Effect of phthalimide as an efficient nucleating agent on the crystallization kinetics of poly(lactic acid)

The effect of phthalimide compound on the nonisothermal and isothermal crystallization behavior of poly(lactic acid) (PLA) was investigated by differential scanning calorimetry (DSC) and polarized optical microscopy. It was found that the incorporation of a small amount of phthalimide promoted the crystallization of PLA significantly. The Avrami model was applied to analyze the isothermal crystallization kinetics. It was found that the Avrami exponent was higher for PLA/phthalimide blends than for neat PLA, indicating a heterogeneous nucleation mechanism. These results indicate that phthalimide may act as an efficient nucleating agent to improve the crystallization of PLA and expand its applications.     

Electrospun poly(aniline‐co‐ethyl 3‐aminobenzoate)/poly(lactic acid) nanofibers and their potential in biomedical applications

Poly(aniline‐co‐ethyl 3‐aminobenzoate) (3EABPANI) copolymer was blended with poly(lactic acid) (PLA) and co‐electrospun into nanofibers to investigate its potential in biomedical applications. The relationship between electrospinning parameters and fiber diameter has been investigated. The mechanical and electrical properties of electrospun 3EABPANI‐PLA nanofibers were also evaluated. To assess cell morphology and biocompatibility, nanofibrous mats of pure PLA and 3EABPANI‐PLA were deposited on glass substrates and the proliferation of COS‐1 fibroblast cells on the nanofibrous polymer surfaces determined. The nanofibrous 3EABPANI‐PLA blends were easily fabricated by electrospinning and gave enhanced mammalian cell growth, antioxidant and antimicrobial capabilities, and electrical conductivity. These results suggest that 3EABPANI‐PLA nanofibrous blends might provide a novel bioactive conductive material for biomedical applications. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011.     

聚丙交酯及其共聚物的研究进展

聚丙交酯（PLA）是一种非常重要的生物医用材料,由于它在体内可降解、无毒、安全,在临床上得到了广泛的应用.为了适应更多、更广的医学应用,要求对聚丙交酯的降解速度、力学性能等进行调节控制,或者要求改善PLA的亲水性、生物相容性、细胞亲和性等等,为此合成了一系列PLA的共聚物,并对其性能进行了研究.本文对上述领域的研究进展进行了综述,结合了作者常年来在PLA共聚物的合成与性能方面的研究,分成四大类进行阐述：（1）丙交酯与其它内酯类的共聚;（2）丙交酯与聚乙二醇类大分子的共聚;（3）丙交酯与带有功能基团单体的共聚;（4）丙交酯与其它天然材料的共聚,并简要地叙述其在医学领域应用的前景.     

Polysaccharide nanocrystals as fillers for PLA based nanocomposites

The development of green nanocomposites based on biopolymers and bio-based nanofillers has attracted over the recent years the attention of academic and industrial research. Indeed, these nanocomposites could replace some oil-derived polymers and thus helping to overcome environmental problems. In this regard, PLA as matrix and polysaccharide nanocrystals as fillers are the most promising components to obtain high-performance green bio-nanocomposites suitable for different applications, particularly for packaging and biomedical applications. Indeed, at present, due to its processability, mechanical and biological properties, as well as its commercial availability, poly(lactic acid) (PLA) possesses one of the highest potentials among biopolymers whereas polysaccharide nanocrystals can be considered the most promising bio-based reinforcements due to their availability, renewability, versatility, biodegradability and high aspect ratio. Aim of this review is to give an overview on the preparation routes and main properties of PLA/polysaccharide nanocomposites highlighting the main differences among the three main polysaccharide nanocrystals, i.e. cellulose, chitin, and starch.     

Graphene oxide crosslinker for the enhancement of mechanical properties of polylactic acid

Polylactic acid (PLA) biopolymer appears to provide environmental advantages over the petroleum-derived polymers but often ends up with limited applications owing to their poor mechanical performance and brittleness. Herein, we present a PLA polymer compatible graphene oxide (GO) based crosslinker with the intention of improving the mechanical properties. Lactic acid (LA) functionalized GO (GO-LA) crosslinker was prepared and had been crosslinked with the PLA chains through a one-step polycondensation reaction. The mechanical properties of the as-synthesized GO crosslinked PLA (GO-C-PLA) were investigated by compression tests and compared with neat PLA, and GO reinforced PLA (GO-PLA) with no crosslinking. With 0.3% of GO-LA crosslinker in GO-C-PLA, the compressive modulus increased by nine times compared to that of the neat PLA. The compressive strength also increased to 46 MPa, which was four times higher than the neat PLA. This strategy for improving the mechanical properties by introducing GO-based crosslinker can be used potentially for many polycondensation polymers and thus be useful for many high-performance applications.     

New emerging trends in synthetic biodegradable polymers - Polylactide: A critique

Polylactide (PLA), the biodegradable synthetic aliphatic polyester, has been studied extensively for a number of applications. With potential applications PLA represents its prospective utility in a number of growing technologies such as orthopedics, drug delivery, sutures, and scaffolds, and have further enhanced the interest of researchers in this novel area. Renewable resource generated monomers possess better mechanical properties and easy processability by conventional methods like thermoforming, injection, and blow molding with non-toxic degradation products, which have made it superior than the other conventional thermoplastics. In order to meet the different performance requirements, PLA can be synthesised by various methods using different catalysts. In this review a collection of more than 100 catalysts for the synthesis of PLA are mentioned, apart from this, efforts have been made to present an updated review on the various aspects of polylactide.