Polyester Block Research Articles

High mechanophore content polyester‐acrylate ABA block copolymers: Synthesis and sonochemical activation

An ABA triblock copolymer with a mechanochemically active gem-dichlorocyclopropane rich polyester block is synthesized via chain extension with polymethylacrylate under SET-LRP conditions. The platform allows for the efficient mechanochemical ring opening of the gDCC groups to 2,3-dichloroalkenes, a promising approach to the synthesis of high mechanophore content polymers with enhanced stability.

Synthesis and characterization of poly(ethylene glycol)‐b‐poly(ε‐caprolactone) copolymers with functional side groups on the polyester block

AbstractThis study reports the successful synthesis of amphiphilic MPEG‐b‐PCL based‐block copolymers bearing benzyloxy and hydroxyl side groups on the PCL block by ring‐opening polymerization of 4‐benzyloxy‐ε‐caprolactone (4‐BOCL) and ε‐caprolactone (ε‐CL) with methoxy PEG (550 g mol−1) as the initiator and Tin(II) 2‐ethylhexanoate (SnOct2) as the catalyst. These copolymers were characterized by differential scanning calorimetry (DSC), 1H NMR, and gel permeation chromatography. The thermal properties (Tg and Tms) of the block copolymers depend on the polymer composition. Incorporating a greater amount of 4‐BOCL and/or ε‐CL was incorporated into the macromolecular backbone causes a decrease Tg, and an increase in Tms. The micellar characteristics in the aqueous phase were investigated by fluorescence spectroscopy, transmission electron microscopy (TEM), and dynamic light scattering (DLS). A lower critical micelle concentration (CMC) was observed in MPEG12‐b‐PBOCL12‐b‐PCL series, which have higher hydrophobic components in the copolymers. However, contrasting results were observed for MPEG12‐b‐PBOCL27‐b‐PCL systems. The micelle exhibited a spindle shape, with an average size of less than 200 nm. A weak drug entrapment efficiency and drug‐loading ability of these micelles were observed. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012

Rapidly thiol-responsive degradable block copolymer nanocarriers with facile bioconjugation

Degradation of amphiphilic block copolymer (ABP) micelles in response to external stimuli (stimuli-responsive degradation) is a desired property in the design of controlled delivery vehicles. Here, a versatile methodology that combines facile carbodiimide coupling polycondensation with controlled radical polymerization to synthesize thiol-responsive degradable ABP micelles is described. These smart micelles consist of a hydrophobic degradable polyester block with disulfide linkages labeled repeatedly along the main chain; more importantly, in response to thiols they exhibit rapid and controlled degradation, thereby leading to enhanced release of encapsulated model drugs. Moreover, the proposed method allows for a facile bioconjugation of hydrophilic coronas using cell-targeting biomolecules during polymerization.

Biocompatible and biodegradable polymersomes as delivery vehicles in biomedical applications

Biocompatible and biodegradable polymersomes are commonly self-assembled from amphiphilic diblock copolymers composed of hydrophilic poly(ethylene glycol) (PEG) or poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) segments and hydrophobic polyester blocks, such as poly(lactic acid) (PLA) or poly(ε-caprolactone) (PCL). Such polymersomes have emerged as promising delivery vehicles for pharmaceutical applications. Presented in this review are summaries of recent developments of biocompatible and biodegradable polymersomes, including self-assembly, encapsulation of various therapeutics, pH-induced hydrolysis for controlled release as well as their functionalization and intelligent design.

Thermogelling polymers composed of poly(cyclohexylenedimethylene adipate) and poly(ethylene glycol)

Block copolymers composed of hydrophilic poly(ethylene glycol) (PEG) and hydrophobic biodegradable polyesters have been reported as thermogelling polymers, because they feature temperature-dependent sol-to-gel or gel-to-sol transitions in aqueous solutions. In this study, a series of thermogelling poly(ethylene glycol methyl ether)-block–poly(cyclohexylenedimethylene adipate)-block–poly(ethylene glycol methyl ether) triblock copolymers and PEG-block–poly(cyclohexylenedimethylene adipate) multiblock copolymers was synthesized by reacting hydroxyl-terminated poly(cyclohexylenedimethylene adipate) (PCA) with poly(ethylene glycol methyl ether) and PEG, respectively, using 1,6-diisocyanatohexane as the coupling agent. Two hydroxyl-terminated PCAs, i.e., poly(1,4-cyclohexylenedimethylene adipate) and poly(1,3/1,4-cyclohexylenedimethylene adipate), were synthesized by the condensation reaction of adipic acid (AA) with 1,4-cyclohexanedimethanol (CHDM) and 1,3/1,4-CHDM, respectively, and used as the hydrophobic polyester blocks of these thermogelling copolymers to compare the effect of crystallinity on the sol-to-gel transition behavior.The polymers were characterized using proton nuclear magnetic resonance, Fourier transform infrared spectroscopy, gel permeation chromatography, differential scanning calorimetry, solubility testing, and rheological analysis. Experimental results revealed that the structure of the PCA block (crystalline vs. amorphous), the molecular weights of the hydrophobic PCA and hydrophilic PEG blocks, and the type of thermogelling polymer (triblock vs. multiblock) influenced the solubility, polymer micelle packing characteristics, maximum storage modulus, and sol-to-gel temperature of the polymers. Among all the samples at 40wt.% aqueous solutions, triblock copolymer TB3 showed sol-to-gel temperature at 22°C, and had the highest maximum storage modulus about 170Pa.

Synthesis of Polyurethane from Poly(3‐hydroxybutyrate) and Poly(p‐dioxanone): Molar Mass Reduction via Sodium Borohydrate

AbstractPoly(3‐hydroxybutyrate) PHB and poly(p‐dioxanone) PPD are examples of promising polymers in tissue engineering. The purpose of this work is to synthesize polyurethanes which combine stereoregular and rigid blocks of PHB with stereoregular and flexible blocks of PPD. In order to guarantee stereoregularity, polyols from PHB and PPD were obtained from mass reduction via sodium borohydrate. This route allows us to obtain bifuncional polyols. The polymer molar mass reduction using this strategy was effective, however secondary and non reactive products with diisocyanate like insaturated acid were formed as shown by mass spectroscopy data. The products of mass reduction were characterized by H1 NMR, FT‐IR, DSC and MALDI‐TOF/MS. The PU's were synthesized reacting the polyols with hexamethylene diisocyanate (HDI) and they were characterized by FT‐IR, H1 NMR, DSC and XRD.The PU obtained from PHB and PPD polyols presents two crystalline phases, corresponding to both polyester blocks. The introduction of flexible segments of PPD in polyurethane, affected the characteristics of crystalline phase formation of PHB, increasing the melting point of this block in comparison with the pure PHB polyol, probably by increasing the crystallization rate.

Functionalized ordered nanoporous polymeric materials: From the synthesis of diblock copolymers to their nanostructuration and their selective degradation

Self-organized block copolymers can be effectively utilized as nanostructured precursors to functionalized ordered mesoporous polymeric materials. Novel nanoporous polystyrene frameworks with carboxylic acid (COOH)-coated pore walls were obtained from the selective degradation of the polyester block in polystyrene- block-poly( d, l-lactide) (PS- b-PLA) diblock copolymers. By resorting to an asymmetric difunctional initiator, an orthogonal atom transfer radical polymerization (ATRP)/ring-opening polymerization (ROP) tandem approach enabled the synthesis of such diblock copolymers with a carboxyl group at the junction point between both blocks. Upon the shear flow induced by a channel die processing, highly oriented copolymers were afforded as evidenced by small-angle X-ray scattering (SAXS). Under mild alkaline conditions, the quantitative hydrolysis of the PLA nanodomains yielded ordered mesoporous materials containing nanoscopic channels lined with chemically accessible and modifiable COOH functional groups. The PS- b-PLA precursors were carefully analyzed by size exclusion chromatography (SEC) and 1H NMR, while the resulting porous frameworks were investigated by scanning electron microscopy (SEM) and nitrogen sorption porosimetry.

Micellar carrier based on methoxy poly(ethylene glycol)-block-poly(ε-caprolactone) block copolymers bearing ketone groups on the polyester block for doxorubicin delivery

Block copolymers of Methoxy poly(ethylene glycol)-block-poly(epsilon-caprolactone) bearing ketone groups (MPEG-b-P(CL-co-OPD)) are synthesized and evaluated for its potential to form micelles containing doxorubicin (DOX), a representative anticancer drug, by using an in vitro method based on membrane dialysis to emulate drug release in vivo. The (1)H NMR spectra of the prepared block copolymers in D(2)O solution exhibit peaks due to the P(OPD-co-CL) in decreased intensity, indicates that the polymers form micelle particles containing the hydrophilic segments in their external parts. The CMC of the copolymer decrease with an increase in the content of ketone groups in the hydrophobic chain. Drug-free and drug-loaded solutions of structurally related copolymers indicate the polymeric aggregation into micellar-type constructs. The size of the drug-loaded micelles is found to be larger than corresponding drug-free micelles. The release rate of MPEG-b-PCL micelles is faster than MPEG-b-P(OPD-co-CL) micelles in pH 7.4 buffered solution and they have a similar release rate in pH 5.0 buffered solution. This study, therefore, confirms the potential of a novel functional block copolymers, Methoxy poly(ethylene glycol)-block-poly(epsilon-caprolactone) bearing ketone Groups, for the formation of polymeric micelles for drug delivery.

Biodegradable amphiphilic poly(ethylene oxide)- block-polyesters with grafted polyamines as supramolecular nanocarriers for efficient siRNA delivery

The RNA interference (RNAi) technology has been successfully used in elucidating mechanisms behind various biological events. However, in the absence of safe and effective carriers for in vivo delivery of small interfering RNAs (siRNAs), application of this technology for therapeutic purposes has lagged behind. The objective of this research was to develop promising carriers for siRNA delivery based on degradable poly(ethylene oxide)- block-polyesters containing polycationic side chains on their polyester block. Toward this goal, a novel family of biodegradable poly(ethylene oxide)- block-poly(ɛ-caprolactone) (PEO- b-PCL) based copolymers with polyamine side chains on the PCL block, i.e., PEO- b-PCL with grafted spermine (PEO- b-P(CL- g-SP)), tetraethylenepentamine (PEO- b-P(CL- g-TP)), or N, N-dimethyldipropylenetriamine (PEO- b-P(CL- g-DP)) were synthesized and evaluated for siRNA delivery. The polyamine-grafted PEO- b-PCL polymers, especially PEO- b-P(CL- g-SP), demonstrated comparable toxicity to PEO- b-PCL in vitro. The polymers were able to effectively bind siRNA, self-assemble into micelles, protect siRNA from degradation by nuclease and release complexed siRNA efficiently in the presence of low concentrations of polyanionic heparin. Based on flow cytometry and confocal microscopy, siRNA formulated in PEO- b-P(CL- g-SP) and PEO- b-P(CL- g-TP) micelles showed efficient cellular uptake through endocytosis by MDA435/LCC6 cells transfected with MDR-1, which encodes for the expression of P-glycoprotein (P-gp). The siRNA formulated in PEO- b-P(CL- g-SP) and PEO- b-P(CL- g-TP) micelles demonstrated effective endosomal escape after cellular uptake. Finally, MDR-1-targeted siRNA formulated in PEO- b-P(CL- g-SP) and PEO- b-P(CL- g-TP) micelles exhibited efficient gene silencing for P-gp expression. The results of this study demonstrated the promise of novel amphiphilic PEO- b-P(CL- g-polyamine) block copolymers for efficient siRNA delivery.

Biodegradable Polycarbonate-b-polypeptide and Polyester-b-polypeptide Block Copolymers: Synthesis and Nanoparticle Formation Towards Biomaterials

The amino poly(trimethylene carbonate)-NHt-Boc (PTMC-NHt-Boc) and poly(epsilon-caprolactone)-NH -Boc (PCL-NHt-Boc) were synthesized by ring-opening polymerization (ROP) of TMC or CL and subsequently deprotected into the corresponding PTMC-NH2 and PCL-NH2. These functional homopolymers were used as macroinitiators for the ROP of gamma-benzyl-L-glutamate N-carboxyanhydride (BLG), consequently, giving the respective diblock copolymers PTMC-b-PBLG and PCL-b-PBLG in almost quantitative yields. The (co)polymers have been characterized by NMR and SEC analyses. DSC and IR studies confirmed the block structure of the copolymers and highlighted a phase separation between the rigid peptide (alpha-helix conformation) and the more flexible polyester segments. The self-assembly and the degradation behaviors of the copolymers depended on the nature of the polyester block and on the copolymer composition. Nanoparticles obtained from PBLG block copolymers were twice smaller ( RH < 100 nm) than those formed from PTMC and PCL homopolymers. Finally, their enzymatic degradation revealed that PTMC nanoparticles degraded faster than those made of PCL.

Comparison of micelles formed by amphiphilic star block copolymers prepared in the presence of a nonmetallic monomer activator

AbstractIn this article, we describe the synthesis of PEG‐b‐polyester star block copolymers via ring‐opening polymerization (ROP) of ester monomers initiated at the hydroxyl end group of the core poly(ethylene glycol) (PEG) using HCl Et2O as a monomer activator. The ROP of ε‐caprolactone (CL), trimethylene carbonate (TMC), or 1,4‐dioxan‐2‐one (DO) was performed to synthesize PEG‐b‐polyester star block copolymers with one, two, four, and eight arms. The PEG‐b‐polyester star block copolymers were obtained in quantitative yield, had molecular weights close to the theoretical values calculated from the molar ratio of ester monomers to PEG, and exhibited monomodal GPC curves. The crystallinity of the PEG‐b‐polyester star block copolymers was determined by differential scanning calorimetry and X‐ray diffraction. Copolymers with a higher arm number had a higher tendency toward crystallization. The crystallinity of the PEG‐b‐polyester star block copolymers also depended on the nature of the polyester block. The CMCs of the PEG‐b‐PCL star block copolymers, determined from fluorescence measurements, increased with increasing arm number. The CMCs of the four‐arm star block copolymers with different polyester segments increased in the order 4a‐PEG‐b‐PCL &lt; 4a‐PEG‐b‐PDO &lt; 4a‐PEG‐b‐PLGA &lt; 4a‐PEG‐b‐PTMC, suggesting a relationship between CMC and star block copolymer crystallinity. The partition equilibrium constant, Kv, which is an indicator of the hydrophobicity of the micelles of the PEG‐polyester star block copolymers in aqueous media, increased with decreasing arm number and increasing crystallinity. A key aspect of the present work is that we successfully prepared PEG‐b‐polyester star block copolymers by a metal‐free method. Thus, unlike copolymers synthesized by ROP using a metal as the monomer activator, our copolymers do not contain traces of metals and hence are more suitable for biomedical applications. Moreover, we confirmed that the PEG‐b‐polyester star block copolymers form micelles and hence may be potential hydrophobic drug delivery vehicles. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 2084–2096, 2008

Degradation Process of Bioresorbable Copolyesters. Microstructure Investigation by NMR and ESI‐MS

AbstractSummary: On the basis of NMR and ESI‐MS spectra completely different ways of degradation process for random and block polyesters copolymers have been observed. PGA/PLA copolymers containing more than 50% of glycolidyl units release short lactidyl microblocks more rapidly than long glycolidyl microblocks. In case of PGA/PCL copolymers chain structure before degradation and mechanism of degradation of two chosen samples are distinctly various despite of low content of GG units in copolymer chain (ca.10%) and lack of differences in NMR spectra. ESI‐MS technique can be useful tool, complementary to NMR method in studying the chain microstructure.

Synthesis and Hydrolysis Behaviour of Poly(ester anhydrides) from Polylactone Precursors Containing Alkenyl Moieties

Hydroxyl-group functional polylactones were prepared and converted to acid- terminated polyesters in a reaction with a series of alkenylsuccinic anhydrides containing 8, 12, or 18 carbons in their alkenyl chains. These polyester precursors were then linked into higher molecular weight poly(ester anhydrides) containing alkenyl moieties in their polyester blocks. The hydrolysis behaviour of the poly(ester anhydrides) was found to depend on the thermal properties of the polyester precursors. For poly(ester anhydrides) prepared from low molecular weight prepolymers with thermal transitions below 37 degrees C, the presence of hydrophobic alkenyl chains in the polyester precursors slowed the rate of weight loss. Poly(ester anhydrides) prepared from higher molecular weight prepolymers showed the opposite weight-loss behaviour; i.e., the crystallinity and thermal transitions of the alkenyl chain-containing poly(ester anhydrides) were low, and the weight loss was faster than for poly(ester anhydrides) without the alkenyl chains. The differences in length of the alkenyl chain, as such, had little effect on the hydrolysis behaviour and thermal properties of the poly(ester anhydrides).

Novel polymeric micelles for hydrophobic drug delivery based on biodegradable poly(hexyl-substituted lactides)

Novel amphiphilic methoxy-poly(ethylene glycol)-poly(hexyl-substituted lactides) block copolymers were synthesized by ring-opening polymerization (ROP) of mono and dihexyl-substituted lactide (mHLA and diHLA) in bulk at 100 °C in the presence of tin(II) 2-ethylhexanoate (Sn(Oct) 2) as catalyst and methoxy-poly(ethylene glycol) (MPEG) as initiator. MPEG-PmHLA and MPEG-PdiHLA copolymers of predictable molecular weights and narrow polydispersities were obtained, as shown by 1H NMR and GPC. DSC experiments showed that the MPEG-PHLA block-copolymer presents a bulk microstructure containing MPEG domains segregated from the PHLA domains. Micelles were successfully prepared from these block copolymers, with sizes ranging from 30 to 80 nm. The critical micellar concentration (CMC) was found to decrease with the increasing number of hexyl groups on the polyester block (MPEG-PLA > MPEG-PmHLA > MPEG-PdiHLA) for copolymers of the same composition and molecular weight. The hydrophobicity of the micelle core in dependence of the number of hexyl groups along the PLA chain was evidenced by absorbance experiments with the incorporation of the dye Nile Red. These novel amphiphilic copolymers are interesting for micellar drug delivery and especially in regard to optimized hydrophobic drug loadings, as it was shown for griseofulvin as a model drug.

The effect of ε-caproyl/ d, l-lactyl unit composition on the hydrolytic degradation of poly( d, l-lactide-ran- ε-caprolactone)-poly(ethylene glycol)-poly( d, l-lactide-ran- ε-caprolactone)

The degradation of P(DLA X - ran-CL Y )- b-PEG- b-P(DLA X - ran-CL Y )s ( P(DLA X - ran-CL Y ): Poly( d, l-lactide- ran- ε-caprolactone), PEG: Poly(ethylene glycol), X: d, l-lactyl unit fraction, Y: ε-caproyl unit fraction) is investigated. The fraction of DLA in the both end blocks is varied while the overall molecular weight and molecular weight of PEG are kept constant. DSC, XRD and GPC are employed to track the degradation process up to 200 days. Also the change in the surface and cross-sectional morphology is provided by SEM micro-photographs. The result of water absorption and weight loss characterization reveals that the incorporation of DLA in the polyester block could be an effective tool to facilitate degradation as well as water absorption. By tracking the change of molecular weight and polydispersity, chain scission and transport or removal of degraded product from the specimen were found to play a complex role in overall degradation.

Biodegradable Nano‐ and Microparticles with Controlled Surface Properties

AbstractMethods suitable for formation of polyester nano‐ and microspheres with controlled surface properties are described. The title nano‐ and microspheres composed of polylactides or poly(ϵ‐caprolactone) were obtained either directly, during dispersion polymerization of corresponding monomers, or by self‐assembly of block copolymers containing polyester blocks. Surface properties of the particles were controlled by using surfactants with required functional groups for dispersion polymerization, by modification of interfacial layer of synthesized particles, and by using for self‐assembly copolymers with appropriate functional groups. Particles with alkyl, amino, hydroxyl, carboxyl, and 4‐(phenyl‐azo)phenyl groups in interfacial layer were obtained. Stability of suspensions of particles and particle's integrity did depend on the nature of functional groups in their interfacial layer and on external stimuli such as pH of suspending medium and irradiation with UV light.

Adsorption of Poly(ethylene oxide)-b-poly(ε-caprolactone) Copolymers at the Silica−Water Interface

The adsorption of amphiphilic poly(ethylene oxide)-b-poly(epsilon-caprolactone) and poly(ethylene oxide)-b-poly(gamma-methyl-epsilon-caprolactone) copolymers in aqueous solution on silica and glass surfaces has been investigated by flow microcalorimetry, small-angle neutron scattering (SANS), surface forces, and complementary techniques. The studied copolymers consist of a poly(ethylene oxide) (PEO) block of M(n) = 5000 and a hydrophobic polyester block of poly(epsilon-caprolactone) (PCL) or poly(gamma-methyl-epsilon-caprolactone) (PMCL) of M(n) in the 950-2200 range. Compared to homoPEO, the adsorption of the copolymers is significantly increased by the connection of PEO to an aliphatic polyester block. According to calorimetric experiments, the copolymers interact with the surface mainly through the hydrophilic block. At low surface coverage, the PEO block interacts with the surface such that both PEO and PCL chains are exposed to the aqueous solution. At high surface coverage, a dense copolymer layer is observed with the PEO blocks oriented toward the solution. The structure of the copolymer layer has been analyzed by neutron scattering using the contrast matching technique and by tapping mode atomic force microscopy. The experimental observations agree with the coadsorption of micelles and free copolymer chains at the interface.

Novel Biodegradable Copolyesters Containing Blocks of Poly(3‐hydroxyoctanoate) and Poly(ε‐caprolactone): Synthesis and Characterization

Novel biodegradable polyester block copolymers have been synthesized by using well-defined poly(3-hydroxyoctanoate) (PHO) oligomers having a hydroxyl end group and an ester end group with M(n) values of 800, 2,500, 5,300, 8,000, or 20,000 as an elastomeric soft segment and poly(epsilon-caprolactone) as a more crystalline segment. These PHO oligomers prepared by methanolysis were subjected to block copolymerization with epsilon-caprolactone. The chemical structure of the copolymers was confirmed by (1)H NMR and (13)C NMR spectroscopy. All the copolyesters are semi-crystalline and two T(g) were observed by differential scanning calorimetry when the molecular weight of the PHO block is about 20,000.

Preparation of methoxy poly(ethylene glycol)/polyester diblock copolymers and examination of the gel‐to‐sol transition

AbstractDiblock copolymers consisting of methoxy poly(ethylene glycol) (MPEG) and poly(ϵ‐caprolactone) (PCL), poly(δ‐valerolactone) (PVL), poly(L‐lactic acid) (PLLA), or poly(lactic‐co‐glycolic acid) (PLGA) as biodegradable polyesters were prepared to examine the phase transition of diblock copolymer solutions. MPEG–PCL and MPEG–PVL diblock copolymers and MPEG–PLLA and MPEG–PLGA diblock copolymers were synthesized by the ring‐opening polymerization of ϵ‐caprolactone or δ‐valerolactone in the presence of HCl · Et2O as a monomer activator at room temperature and by the ring‐opening polymerization of L‐lactide or a mixture of L‐lactide and glycolide in the presence of stannous octoate at 130 °C, respectively. The synthesized diblock copolymers were characterized with 1H NMR, IR, and gel permeation chromatography. The phase transitions for diblock copolymer aqueous solutions of various concentrations were explored according to the temperature variation. The diblock copolymer solutions exhibited the phase transition from gel to sol with increasing temperature. As the polyester block length of the diblock copolymers increased, the gel‐to‐sol transition moved to a lower concentration region. The gel‐to‐sol transition showed a dependence on the length of the polyester block segment. According to X‐ray diffraction and differential scanning calorimetry thermal studies, the gel‐to‐sol transition of the diblock copolymer solutions depended on their degrees of crystallinity because water could easily diffuse into amorphous polymers in comparison with polymers with a crystalline structure. The crystallinity markedly depended on both the distinct character and composition of the block segment. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 5784–5793, 2004

Controlled synthesis of biodegradable lactide polymers and copolymers using novel in situ generated or single-site stereoselective polymerization initiators

Polylactides and their copolymers are key biodegradable polymers used widely in biomedical, pharmaceutical and ecological applications. The development of synthetic pathways and catalyst/initiator systems to produce pre-designed polylactides, as well as the fundamental understanding of the polymerization reactions, has continuously been an important topic. Here, we will address the recent advances in the ring-opening polymerization of lactides, with an emphasis on the highly versatile in situ generated initiator systems and single-site stereoselective initiators. The in situ generated initiators including in situ formed yttrium, calcium and zinc alkoxides all have been shown to bring about a rapid and living polymerization of lactides under mild conditions, which facilitated the preparation of a variety of advanced lactide-based biomaterials. For example, well-defined di- and tri-block copolymers consisting of hydrophilic poly(ethylene glycol) blocks and hydrophobic polyester blocks, which form novel biodegradable polymersomes or biodegradable thermosensitive hydrogels, have been prepared. In the past few years, significant progress has also been made in the area of stereoselective polymerization of lactides. This new generation of initiators has enabled the production of polylactide materials with novel microstructures and/or properties, such as heterotactic (–RRSSRRSSRRSS–) polylactide, crystalline syndiotactic (–RSRSRSRSRSRS–) polylactide and isotactic stereoblock (–RnSnRnSn –) polylactide, exhibiting a high melting temperature. The recently developed polymerizations using in situ generated initiators and stereoselective polymerizations have no doubt opened a brand-new avenue for the design and exploration of polylactides and their copolymers.