PLLA Block Research Articles

Single crystals morphology of biodegradable double crystalline PLLA-b-PCL diblock copolymers

The morphology of solution grown single crystals of a series of double crystalline diblock copolymers derived from l-lactide and ɛ-caprolactone has been investigated by means of transmission electron microscopy. The copolymers had a variable composition with a poly(l-lactide) weight percentage that ranged between 81 and 10%. All samples had a low polydispersity index (1.4–1.1) and a similar number average molecular weight (20,000–35,000g/mol).Bulk crystallization and melting behaviour of diblock copolymers were evaluated by DSC and the results demonstrated the double crystalline nature of the samples. Fractionated crystallization clearly occurred in copolymers having an intermediate composition.Isothermal crystallizations were performed in dilute n-hexanol solutions at temperatures that ranged between 80 and 50°C. Crystal morphologies were dependent on the crystallization temperature and even on the composition. Thus, the inability of poly(ɛ-caprolactone) (PCL) blocks to crystallize between 80 and 70°C rendered lozenge, truncated and spindle-shaped crystals associated to the poly(l-lactide) (PLLA) block. These usually had thicker edges due to PLLA overgrowths that mainly took place in their periphery. However, an overgrowth of irregular PCL crystals during subsequent cooling and crystallization at room temperature was also detected. Complex morphologies constituted by lamellar crystals of both PCL and PLLA blocks were developed at intermediate temperatures (70–65°C), whereas elongated hexagonal morphologies mainly associated to the PCL block were detected at the lowest crystallization temperature. In general, electron diffraction patterns showed for all samples’ reflections associated to both poly(ɛ-caprolactone) and poly(l-lactide) (α-form) crystals. The relative intensity between the two types of reflections varied according to the copolymer composition.

Orthogonal Crystal Orientation in Double-Crystalline Block Copolymer

In this study, we explore the orientation of crystals formed within the lamellar domains of a diblock copolymer composed of two crystallizable blocks, that is, poly(l-lactide)-block-polyethylene (PLLA-b-PE). The orientation of both PLLA and PE crystals with respect to the lamellar interface was examined under two types of crystallization condition with a broad range of crystallization temperatures (Tc). The first type was the “two-stage crystallization”, where the PLLA block was allowed to crystallize before PE. The second was the “one-stage crystallization”, where PLLA and PE blocks competed to crystallize. A homeotropic crystal orientation was always observed for the PLLA crystals, with the crystalline stems lying parallel to the lamellar normal regardless of the crystallization condition, except when Tc approached the glass-transition temperature of PLLA, where the orientation became random. A homogeneous crystal orientation with the PE crystalline stems oriented perpendicular to the lamellar normal wa...

Synthesis and Thermal Properties of Linear Amphiphilic Diblock Copolymers of l-Lactide and 2-Dimethylaminoethyl Methacrylate

A well-defined series of nine poly(l-lactide)-b-(2-dimethylaminoethyl methacrylate) (PLLA-b-PDMAEMA) linear diblock copolymers with low polydispersity were prepared by ring-opening polymerization of LLA using 4-isopropylbenzyl alcohol and tin octoate as the initiating system, conversion of the OH-terminated PLLA into Br-terminated macroinitiators (5, 13, and 19 kg/mol), followed by atom transfer radical polymerization of DMAEMA (to obtain one-half, equal, and twice the molecular weight of each PLLA block). Compositional analysis and molecular weight characterization were done using NMR, SEC–LS, TGA, polarimetry, and PDMAEMA quaternization/precipitation to test for residual PLLA homopolymer. DSC investigations indicate that low molecular weight amorphous PLLA or PDMAEMA blocks (less than or equal to ca. 5000 g/mol) are miscible in the second block. Compared to the parent PLLA homopolymers, PLLA crystallization in the block copolymers is significantly retarded, whereas the degree of crystallinity is only mildly affected and melting points are reduced only for the low molecular weight miscible blocks.

Morphologies and structures in poly(l-lactide-b-ethylene oxide) copolymers determined by crystallization, microphase separation, and vitrification

Morphologies and structures determined by crystallization of the blocks, microphase separation of the copolymers, and vitrification of PLLA block in poly(l-lactide-b-ethylene oxide) (PLLA-b-PEO) copolymers were investigated using microscopic techniques and synchrotron small angle X-ray scattering. The PLLA-b-PEO copolymer films were crystallized from two different annealing processes: melt crystallization (process A) or crystallized from glass state of PLLA block after quenching from melt state (process B). The relationship between the crystalline morphology and microstructure of the copolymers were explored using SAXS. The morphology and phase structure are predominated by crystallization of PLLA block, and greatly influenced by microphase separation of the copolymers. In process B, lozenge-shape and truncated lozenge-shaped PLLA crystals of nanometer scale can be observed. The crystalline morphology is markedly affected by the microstructure formed during the annealing process. Star-shaped morphologies stacked with PLLA single crystals were observed.

Stereocomplex‐induced gelation properties of polylactide/poly(ethylene glycol) diblock and triblock copolymers

AbstractThe ring‐opening polymerization of L‐ or D‐lactide was realized in the presence of dihydroxyl or monomethoxy poly(ethylene glycol) (PEG) with a number‐average molecular weight of 2000. The resulting low‐molar‐mass poly(L‐lactide) (PLLA)/PEG and poly(D‐lactide) (PDLA)/PEG triblock and diblock copolymers were characterized with nuclear magnetic resonance (NMR), differential scanning calorimetry, size‐exclusion chromatography, and X‐ray diffractometric analysis. Bioresorbable hydrogels were successfully prepared from aqueous solutions containing both copolymers because of interactions and stereocomplexation between the PLLA and PDLA blocks. Gelation was evaluated with the tube inverting method and rheological measurements. A phase diagram was realized with gel–sol transitions as a function of concentration. The rheological properties of the hydrogels were investigated under various conditions through changes in the copolymer concentration, temperature, time, and frequency. It was concluded that the hydrogels constituted a dynamic and evolutive system because of the continuous formation/destruction of crosslinks and degradation. Further studies are underway to elucidate the degradation behavior and the potential of these substances as drug carriers or cell culture scaffolds. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011

Helical assemblies from chiral block copolymers

Helical assemblies from chiral block copolymers (BCPs*) have been intensively studied due to their unique hierarchical architectures arising from the interplay of various secondary interactions. Helical architectures from BCP* self-assembly in solution have been found in peptide-based and lactide-based BCPs*. Inspired by the concept of chiral information transfer from the molecular level to macroscopic features, polystyrene-block-poly(L-lactide) (PS-PLLA) BCPs* composed of an achiral PS block and a chiral PLLA block has been designed for fabrication of helical assemblies. In contrast to a variety of helical assemblies resulting from solution, a helical phase (H*) having hexagonally packed helical PLLA microdomains in a PS matrix can be obtained in bulk by introducing chirality starting from the molecular level for BCP self-assembly. Phase behavior was examined and phase transitions from the H* phase to both cylinder and gyroid phases were found after long-time annealing, suggesting that the H* phase is a long-lived metastable phase. The morphologies of the H* phase can be manipulated into stretched helices (eventually leading to straight cylinders) by applying the stimulation (i.e., crystallization) so as to result in spring-like behavior. Also, by taking advantage of the degradable character of polylactides, a nanoporous PS polymer can be obtained after PLLA hydrolysis to be used as a template for fabrication of helical nanohybrids.

Enhancing mechanical properties of thermoplastic polyurethane elastomers with 1,3-trimethylene carbonate, epsilon-caprolactone and L-lactide copolymers via soft segment crystallization

Multiblock thermoplastic polyurethane elastomers based on random and triblock copolymers were synthesized and studied. Dihydroxyl-terminated random copolymers were prepared by ring opening copolymerization of !-caprolac- tone (CL) and 1,3-trimethylene carbonate (TMC). The triblock copolymers were synthesized by using these random copolymers as macro-initiator for the L-lactide (L-LA) blocks. These random and triblock copolymers were further reacted with 1,6-hexamethylene diisocyanate (HMDI) and chain extended by 1,4-butanediol (BDO). The polymer structure and chemical composition were characterized by 1 H NMR 13 C NMR and SEC. Their thermal and mechanical properties were studied by using DSC and Instron microtester. Multiblock polyurethanes based on random PCL-co-PTMC copolymers showed strain recovery improvement with increasing PCL content. However, these polyurethanes were unable to sustain deformation at body temperature due to the melting of PCL crystals and low hard segments content. With the presence of crystallizable PLLA blocks, mechanical properties were improved at body temperature without compromising their good strain recovery.

Inorganic Gyroid with Exceptionally Low Refractive Index from Block Copolymer Templating

Nanoporous polymers with gyroid nanochannels can be fabricated from the self-assembly of degradable block copolymer, polystyrene-b-poly(l-lactide) (PS-PLLA), followed by the hydrolysis of PLLA blocks. A well-defined nanohybrid material with SiO2 gyroid nanostructure in a PS matrix can be obtained using the nanoporous PS as a template for sol-gel reaction. After subsequent UV degradation of the PS matrix, a highly porous inorganic gyroid network remains, yielding a single-component material with an exceptionally low refractive index (as low as 1.1).

Amphiphilic Cationic [Dendritic poly(L‐lysine)]‐block‐poly(L‐lactide)‐block‐[dendritic poly(L‐lysine)]s in Aqueous Solution: Self‐Aggregation and Interaction with DNA as Gene Delivery Carriers

A new series of triblock [dendritic poly(L-lysine)]-block-PLLA-block-[dendritic poly(L-lysine)]s (DL(2) -PLLA-DL(2) ) with PLLA block lengths of 11.5-26.5 and double 2-generation PLL dendrons DL(2) as model cationic amphiphiles were synthesized and characterized. Their CAC, self-aggregation and plasmid DNA binding affinities in pure water and PBS were studied. The PLLA block length dependence of particle size, morphology and ξ potential for organized pDNA/amphiphile polyplex aggregates were examined. Finally, toxicities of these DL(2) -PLLA-DL(2) amphiphiles and their polyplexes were assayed by MTT with HeLa, SMMC-7721 and COS-7 cells, and COS-7 cell luciferase and eGFP gene transfection efficacies with these amphiphiles as the delivery carriers were investigated.

Development of Injectable Biodegradable Multi‐Arms PEG‐Based Hydrogels: Swelling and Degradation Investigations

AbstractSummary: Injectable biodegradable hydrogels have been developed to determine the efficacy of biomaterials for the treatment of periodontitis through control delivery of bone‐healing bioactives. The hydrogels were prepared from the PEG‐ylated macromer of Boltorn™ H20 (BH20) and an acrylated triblock copolymer of polylactide‐polyethylene glycol (2k)‐polylactide (PLA) in various molar ratios using ammonium persulfate and sodium ascorbate as a free radical initiating system. Preliminary investigations involving the synthesis of PLA hydrogels with different PLLA block lengths were studied in order to determine the swelling ratios and degradation rates of the biodegradable component of the hydrogels prior to copolymerization with BH20. The swelling and degradation studies of PLA with PEG diacrylate (FW 700) hydrogels were established in phosphate buffered saline (PBS) at 37 °C, pH 7.4 and in water (pH ∼5.5). They have been shown to have low swelling ratios (Qmax = 4.4 to 3.6) and degradation times of 20–30 days. The swelling and degradation parameters were found to be dependent on the molar ratio of the PEG diacrylate to PLA in the copolymer.

Thermo-responsive hydrogels based on highly branched poly(ethylene glycol)–poly( l-lactide) copolymers

Highly branched poly(ethylene glycol)–poly( l-lactide) (PEG–PLLA) copolymers were synthesized by a coupling reaction of eight-arm amine-functionalized PEG and macromonomers having 2 PLLA arms and a N-hydroxysuccinimide activated ester group at the branching point. A coupling efficiency of approximately 50% was achieved. Copolymer solutions in water (⩾4 wt.%) showed a phase transition from gel to sol upon increasing the temperature. The critical gelation concentration at 20 °C decreased with increasing PLLA block length. The gel–sol transition of a 12 wt.% aqueous copolymer solution increased from 4 °C for a copolymer with PLLA blocks with 3 repeating lactide units per arm to 38 °C for a copolymer with PLLA blocks with 5 repeating lactide units per arm. Furthermore, the gel–sol transition temperature increased with increasing copolymer concentration, and could be tuned closely to body temperature, which makes these hydrogels interesting as injectable systems for in situ gel formation.

Synthesis of star‐shaped poly(ε‐caprolactone)‐b‐poly(L‐lactide) copolymers: From star architectures to crystalline morphologies

AbstractHexa‐armed star‐shaped poly(ε‐caprolactone)‐block‐poly(L‐lactide) (6sPCL‐b‐PLLA) with dipentaerythritol core were synthesized by a two‐step ring‐opening polymerization. GPC and 1H NMR data demonstrate that the polymerization courses are under control. The molecular weight of 6sPCLs and 6sPCL‐b‐PLLAs increases with increasing molar ratio of monomer to initiator, and the molecular weight distribution is in the range of 1.03–1.10. The investigation of the melting and crystallization demonstrated that the values of crystallization temperature (Tc), melting temperature (Tm), and the degree of crystallinity (Xc) of PLLA blocks are increased with the chain length increase of PLLA in the 6sPCL‐b‐PLLA copolymers. On the contrary, the crystallization of PCL blocks dominates when the chain length of PLLA is too short. According to the results of polarized optical micrographs, both the spherulitic growth rate (G) and the spherulitic morphology are affected by the macromolecular architecture and the length of the block chains. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010

Macromol. Rapid Commun. 17/2010

Back Cover: The image presents the synthesis and characterization of aggregates and intracellular distribution of fluorescently labeled P(HPMA)-b-P(LLA) block copolymers. The reactive precursor polymer P(PFMA)-b-P(LLA) enables the incorporation of various functionalities, while the biodegradable PLLA block can be used to encapsulate bioactive agents. More details can be found in the article by M. Barz, F. K. Wolf, F. Canal, K. Koynov, M. J. Vicent, H. Frey, and R. Zentel* on page 1492.

Development of Worm-like Polymeric Drug Carriers with Multiple Ligands for Targeting Heterogeneous Breast Cancer Cells

In this study, wormorm-like polymeric micelles were construted from poly(L-lactic acid)-b-poly(ethyelen glycol) (PLLA-b-PEG) block copolymers via worm-like (or cylindrical) self- assembly that consisted of a relatively long PLLA block (<TEX>$M_n$</TEX> 7K Daltons) at the core and a relatively short PEG block (<TEX>$M_n$</TEX> 2K Daltons) as the shell. Several cancer-targeting moieties (such as folate, cobalamin, and cyclic arginine-glycine-aspartic (RGD) peptide) were chemically coupled with the succinylated or maleimided PEG block of PLLA-b-PEG to act as a cancer cell-specific targeting ligand for breast cancer. The worm-like micelles with muplite cancer cell-specific ligands proved to be successful in recognizing different breast cancer cells at once. This has the potential to aid in cancer-specific drug delivery and to be used as an effective treatment for breast cancer.

Preparation of multifunctional polymeric micelles for antiviral treatment

In this study, a poly(L-lactic acid)-b-poly(ethylene glycol) (PLLA-b-PEG) diblock copolymer modified with a sialic acid derivative (methyl-b-neuraminic acid: mNA) was prepared for the development and application of a therapeutic nanosystem with multifunctionality. The terminal carboxyl group of PEG was coupled with mNA via N,N′-dicyclohexyl carbodiimide (DCC)-and N-hydroxysuccinimide (NHS)-mediated amide formation. Polymeric micelles were formed using the diafilteration method at pH 7.4, which resulted in a micelle self-assembly with the PLLA block at the core and PEG-mNA block on the shell. An anionic charge was formed on the surface of the micelle at physiological pH (∼pH 7.4) due to mNA. Amantadine (AMT), a model drug for antiviral treatment, was loaded into the micellar core. These micelles were expected to exhibit multiple therapeutic activity that originated from the antiviral activity of mNA on the shell and the sustained release of AMT from the micellar core.

Crystallization Kinetics and Morphology of Biodegradable Double Crystalline PLLA-b-PCL Diblock Copolymers

The crystallization kinetics and morphology of biodegradable and double crystalline poly(l-lactide)-b-poly(ε-caprolactone) diblock copolymers (PLLA-b-PCL) was studied in a wide composition range by differential scanning calorimetry (DSC) and polarized light optical microscopy (PLOM). The two blocks were found to be partially miscible according to the variations of their thermal transitions with composition. PLOM results showed that PLLA crystallizes in a wide composition range with a spherulitic superstructural morphology. Only when the PLLA content is as low as 10 wt % are axialites formed. These results were in good agreement with the overall crystallization kinetics obtained by DSC isothermal experiments and analyzed by the Avrami equation. Both overall crystallization rates and spherulitic growth rates of the PLLA block decrease with PCL content because PCL acts as a diluent for the PLLA block in view of their miscibility. Reorganization processes revealed as double melting peaks for the PLLA block (not observed for the PLLA homopolymer) were observed during heating scans performed after isothermal crystallization. The reorganization ability of the PLLA block was found to increase with PCL content, a fact that quantified the perturbation caused by molten PCL block chains during the isothermal crystallization of the PLLA block. The PCL block crystallizes within previously formed PLLA spherulites or axialites. Despite the partial miscibility, unexpected and novel fractionated crystallization of the PCL occurs at contents of PCL between 40 and 19 wt %. For the lowest PCL content (i.e., 19%), a homogeneous nucleation process was detected, as indicated by the large supercooling needed for crystallization and by the first-order crystallization kinetics obtained (i.e., Avrami index close to 1). Because of the partial miscibility, the glass-transition temperature of the PLLA block (Tg,PLLA) decreases with PCL addition, so at PCL contents lower than 40 wt %, the Tg,PLLA values are close to or higher than the crystallization temperature of the PCL block. Therefore, PCL fractionated crystallization is induced by hard confinement of the PLLA amorphous and crystalline regions. This is the first time that a homogeneous nucleation process has been documented for a crystallizable component in a miscible or weakly segregated diblock copolymer. The PCL block can also be nucleated by previously formed PLLA crystals depending on the crystallization degree of the PLLA, which was varied by self-nucleation experiments. The crystallization rate of PCL strongly decreased with increasing PLLA content.

Synthesis and properties of high‐molecular‐weight stereo di‐block polylactides with nonequivalent D/L ratios

AbstractDi‐stereoblock polylactides (di‐sb‐PLA: PLLA‐b‐PDLA) having high molecular weight (Mn &gt; 100 kDa) were successfully synthesized by two‐step ring‐opening polymerization (ROP) of L‐ and D‐lactides using tin(2‐ethylhexanoate) as a catalyst. By optimizing the polymerization conditions, the block sequences were well regulated at non‐equivalent feed ratios of PLLA and PDLA. This synthetic method consisted of three stages: (1) polymerization of either L‐ or D‐lactide to obtain a PLLA or PDLA prepolymer with a molecular weight less than 50 kDa, (2) purification of the obtained prepolymer to remove residual lactide, and (3) polymerization of the enantiomeric lactide in the presence of the purified prepolymer. Their 13C and 31P NMR spectra of the resultant di‐sb‐PLAs strongly supported their di‐stereo block structure. These di‐sb‐PLAs, having weight‐average molecular weights higher than 150 kDa, were fabricated into polymer films by solution casting and showed exclusive stereocomplexation. The thermomechanical analysis of the films revealed that their heat deformation temperature was limited probably because of their low crystallinity owing to the non‐equivalent PLLA/PDLA ratio. The blend systems of the di‐sb‐PLAs having complementary stereo‐sequences (the one with a long PLLA block and the other with long PDLA block) were also prepared and characterized to enhance the sc crystallinity. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 794–801, 2010

Controlled preparation of poly(ethylene glycol) and poly(L -lactide) block copolymers in the presence of a monomer activator

Polymerization of L-lactide (LA) was performed in the presence of trifluoromethanesulfonic acid (CF3SO3H) via an activated monomer mechanism to synthesize various block copolymers composed of polyethyleneglycol (PEG) and poly(L-lactide) (PLLA). The PLLAs obtained had molecular weights close to theoretical values calculated from LA/PEG molar ratios and exhibited monomodal GPC curves. A 1H NMR spectroscopic study showed that the LA carbonyl carbon signal exhibited a change in chemical shift to lower field, caused by electron delocalization of the carbonyl carbon by CF3SO3H. We successfully prepared PEG and PLLA block copolymers using this activated monomer mechanism. We concluded that synthesis proceeded by LA ring-opening polymerization caused by PEG in the presence of CF3SO3H to yield PEG and PLLA block copolymers. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 5917–5922, 2009

Dendritic Superstructures and Structure Transitions of Asymmetric Poly(l-lactide-b-ethylene oxide) Diblock Copolymer Thin Films

The evolution of morphologies of isothermally crystallized thin films with different thicknesses of poly(L-lactide-b-ethylene oxide) diblock copolymer was observed by optical microscopy (OM) and atomic force microscopy (AFM). Dendritic superstructures stacked with lamellae were investigated in thin films with approximately 200 nm to approximately 400 nm thickness. The lamellar structure was a lozenge- or truncated-lozenge-shaped single crystal of PLLA confirmed by AFM observations. The contour of the dendritic superstructures is hexagonal, and two types of sectors, [110] and [100], can be classified in terms of the chain-folding and crystal growth directions. These phenomena are due to the interplay of the crystallization of the PLLA block, the microphase separation of the block copolymer, and the effect of the film thickness. The growth process of the superstructure can be classified into three steps: the growth of the main branches, the growth of the secondary side branches along the main branch, and the tertiary side branches. PLLA growth rates decrease in copolymer films thinner than 1 microm. Layer-layer phase structure of the copolymer driven by the crystallization of PLLA and the microphase separation of the copolymer appears to be a key factor explaining the crystallization and morphological behavior of this system.

Dendritic Poly(l-lysine)-b-Poly(l-lactide)-b-Dendritic Poly(l-lysine) Amphiphilic Gene Delivery Vectors: Roles of PLL Dendritic Generation and Enhanced Transgene Efficacies via Termini Modification

As an effort to prepare new efficient gene delivery vectors, we have recently developed and reported an amphiphilic dendritic poly(L-lysine)-b-poly(L-lactide)-b-dendritic poly(L-lysine) D(2)-PLLA-D(2) with two-generation PLL dendrons and a PLLA block. In this work, we continued to explore the roles of dendritic PLL generation in DNA binding and intracellular delivery of gene, and a new series of amphiphilic dendritic poly(L-lysine)-b-poly(L-lactide)-b-dendritic poly(L-lysine)s D(n)-PLLA-D(n) (n = 3-5) were synthesized and were structurally characterized. Furthermore, plasmid DNA binding affinity for these cationic amphiphiles was examined by agarose gel electrophoresis and fluorescence titration assay in pure water and PBS buffer solution containing 150 mM NaCl (pH = 7.4), respectively. By dynamic light scattering (DLS) and transmission electronic microscopy (TEM), the interaction and complexation in between were investigated, concerning the DNA/vector polyplex particle morphologies and zeta potentials. Utilizing a human hepatocellular carcinoma cell-line SMMC-7721, cell toxicity, and gene transfection in vitro were explored. To further improve transgene efficiency for these synthetic cationic amphiphiles as gene delivery vectors, new structural DE(n)-PLLA-DE(n) (n = 2-3) were prepared through an amino termini modification of the D(n)-PLLA-D(n) (n = 2-3) with less toxic 4,7,10,13-tetraazatridecanoic acids, and gene transfection with these DE(n)-PLLA-DE(n) (n = 2-3) was examined with an alternative human gastric carcinoma cell-line HGC-27. As a result, the high plasmid DNA binding affinity, low cytotoxicity, and much enhanced transgene efficacy suggest a new possible clue to design effective synthetic gene delivery vectors with amphiphilic skeleton and less toxic polyamine building blocks.