Synthesis of biodegradable copolymers with low‐toxicity zirconium compounds. III. Synthesis and chain‐microstructure analysis of terpolymer obtained from L‐lactide,glycolide, and ϵ‐caprolactone initiated by zirconium(IV) acetylacetonate

Zirconium(IV) acetylacetonate [Zr(acac)₄] is a very good initiator for the terpolymerization of glycolide with L‐lactide and ?‐caprolactone. The microstructure of the obtained terpolymer was determined by NMR spectroscopy and then compared with terpolymers obtained in the presence of stanous(II) octoate [Sn(oct)₂]. Samples obtained with Zr(acac)₄ were characterized by a segmental‐chain microstructure. Apart from relatively long lactidyl microblocks, there were also segments made of random copolymer of glycolide with lactide. Such a structure is formed as a result of strong transesterification caused by active caproyl chain endings attacking the glycolidyl groups. Domination of this type of transestrification is shown. The growth of terpolymer chains and the influence of transesterification on gradual changes of the microstructure of the forming terpolymer chain were examined. Significant differences among glycolide, lactide, and the least reactive caprolactone were observed. The results of differential scanning calorimetric examinations of the obtained terpolymers are presented. Differences between the structures of random terpolymers obtained during terpolymerization initiated by Sn(oct)₂ and those obtained by Zr(acac)₄ influence their thermal properties. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 3129–3143, 2002     

Poly(ϵ‐caprolactone‐b‐glycolide) and poly(D,L‐lactide‐b‐glycolide) diblock copolyesters: Controlled synthesis,characterization, and colloidal dispersions

Living ω‐aluminum alkoxide poly‐ϵ‐caprolactone and poly‐D,L ‐lactide chains were synthesized by the ring‐opening polymerization of ϵ‐caprolactone (ϵ‐CL) and D,L ‐lactide (D,L ‐LA), respectively, and were used as macroinitiators for glycolide (GA) polymerization in tetrahydrofuran at 40 °C. The P(CL‐b‐GA) and P(LA‐b‐GA) diblock copolymers that formed were fractionated by the use of a selective solvent for each block and were characterized by ¹H NMR spectroscopy and differential scanning calorimetry analysis. The livingness of the operative coordination–insertion mechanism is responsible for the control of the copolyester composition, the length of the blocks, and, ultimately, the thermal behavior. Because of the inherent insolubility of the polyglycolide blocks, microphase separation occurs during the course of the sequential polymerization, resulting in a stable, colloidal, nonaqueous copolymer dispersion, as confirmed by photon correlation spectroscopy. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 39: 294–306, 2001     

Effect of comonomer on thermal/mechanical and shape memory property of L‐lactide‐based shape‐memory copolymers

In this study, three kinds of L ‐lactide‐based copolymers, poly(lactide‐co‐glycolide) (PLGA), poly(lactide‐co‐p‐dioxanone) (PLDON) and poly(lactide‐co‐caprolactone) (PLC), were synthesized by the copolymerization of L ‐lactide (L) with glycolide (G), or p‐dioxanone (DON) or ε‐caprolactone (CL), respectively. The copolymers were easily soluble in common organic solvents. The compositions of the copolymers were determined by ¹H‐NMR. Thermal/mechanical and shape‐memory properties of the copolymers with different comonomers were compared. Moreover, the effect of the chain flexibility of the comonomers on thermal/mechanical and shape‐memory properties of the copolymers were investigated. The copolymers with appropriate lactyl content showed good shape‐memory properties where both the shape fixity rate (R_f)and the shape recovery rate (R_r) could exceed 95%. It was found that the comonomers with different flexible molecular chain have different effects on their thermal/mechanical and shape‐memory properties. Among them, PLGA has the highest mechanical strength and recovery rate while PLC copolymer has high recovery rate when the lactyl content exceeded 85% and the lowest transition temperature (T_trans). Copyright © 2007 John Wiley & Sons, Ltd.     

Novel functionalization routes of poly(ϵ‐caprolactone)

The aluminum alkoxide mediated ring opening polymerization of functional lactones, such as γ‐ethylene ketal‐ϵ‐caprolactone (TOSUO), γ‐(triethylsilyloxy)‐ϵ‐caprolactone (SCL) and γ‐bromo‐ϵ‐caprolactone (γBrCL), is a versatile route to polyesters containing ketal, ketone, alcohol and bromide groups. As result of living polyaddition mechanism, random and block copolymerization of ϵCL and γBrCL has been successfully carried out. The reactivity ratios are quite similar (1.08 for ϵ‐CL, and 1.12 for γBrCL). These random copolymers are semicrystalline when they contain less than 30 mol% of γBrCL, otherwise they are amorphous. No transesterification reaction occurs during the sequential polymerization of ϵ‐CL and γBrCL leading to block copolymers. Reaction of poly(ϵCL‐co‐γBrCL) with pyridine provides quantitatively a polycationic polyester. Furthermore, the reaction of this random copolymer with 1,8‐diazabicyclo[5.4.0] undec‐7‐ene (DBU) is a route to unsaturated polyesters, whose the non conjugated double bonds can be quantitatively converted into epoxides by reaction with m‐chloroperbenzoic acid (mCPBA). No chain degradation is detected during these derivatization reactions of poly(ϵCL‐co‐γBrCL).     

Relationship among drug delivery behavior,degradation behavior and morphology of copolylactones derived from glycolide,l‐lactide and ε‐caprolactone

A series of copolylactones was synthesized by ring‐opening copolymerization of glycolide, L ‐lactide and ?‐caprolactone, using stannous octoate as catalyst. The in vitro degradation behaviors of them were studied and data demonstrated different degradation rates which mainly depended on the compositions. Investigation of the 5‐fluorouracil (5‐Fu) release from these copolylactones revealed that the composition, degradation rate and the morphology of the polymeric matrix played an important role on the drug release kinetics. A sustained 5‐Fu release without initial time lag was obtained from random poly(lactide‐co‐glycolide‐co‐caprolactone) (r‐PGLC) drug carrier, and it differed from the cases of polylactide (PLA) or random poly(lactide‐co‐glycolide) (PLGA), which usually showed an initial time lag or biphasic drug release behavior. It was due to the low glass transition temperature (T _g) of the r‐PGLC and the drug would diffuse faster in rubbery state under the experimental temperature. Furthermore, a significant change in the drug release behavior of r‐PGLC was observed when the temperatures were changed around the T _g of the drug carrier, which implied that the drug release behavior could be regulated by adjusting the morphology of the drug carrier. Copyright © 2002 John Wiley & Sons, Ltd.     

Block and random copolymerization of ε‐caprolactone,L‐, and rac‐lactide using titanium complex derived from aminodiol ligand

A series of di‐ and triblock copolymers [poly(L ‐lactide‐b‐ε‐caprolactone), poly(D,L ‐lactide‐b‐ε‐caprolactone), poly(ε‐caprolactone‐b‐L ‐lactide), and poly(ε‐caprolactone‐b‐L ‐lactide‐b‐ε‐caprolactone)] have been synthesized successfully by sequential ring‐opening polymerization of ε‐caprolactone (ε‐CL) and lactide (LA) either by initiating PCL block growth with living PLA chain end or vice versa using titanium complexes supported by aminodiol ligands as initiators. Poly(trimethylene carbonate‐b‐ε‐caprolactone) was also prepared. A series of random copolymers with different comonomer composition were also synthesized in solution and bulk of ε‐CL and D,L ‐lactide. The chemical composition and microstructure of the copolymers suggest a random distribution with short average sequence length of both the LA and ε‐CL. Transesterification reactions played a key role in the redistribution of monomer sequence and the chain microstructures. Differential scanning calorimetry analysis of the copolymer also evidenced the random structure of the copolymer with a unique T_g. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Biodegradable shape‐memory polymer—polylactide‐co‐poly(glycolide‐co‐caprolactone) multiblock copolymer

In this study, biodegradable shape‐memory polymers—polylactide‐co‐poly(glycolide‐co‐caprolactone) multiblock (PLAGC) copolymers—were synthesized by the coupling reaction of both macrodiols of polylactide (PLLA‐diol) and poly(glycolide‐co‐caprolactone) (PGC‐diol) in the presence of 1,6‐hexanediisocyanate as coupling agent. The copolymers formed were found to be thermoplastic and easily soluble in common solvents. The compositions of the copolymers were determined by ¹H‐NMR and the influences of segment lengths and contents of both macrodiols on the properties of the PLAGC copolymers were investigated. It was found that the copolymers had adjustable mechanical properties which depended on contents and segment lengths of both macrodiols. The copolymers showed such good shape‐memory properties that the strain fixity rate (R_f) and the strain recovery rate (R_r) exceed 90%. By means of adjusting the compositions of the copolymers, PLAGC copolymers with transition temperatures around 45°C could be obtained. The degradation rate determination showed that the PLAGC copolymers have fast degradation rates, the mechanical strengths of the PLAGC copolymers would be completely lost within 1–2 months depending on molecular weights and contents of the both segments of PLLA and PGC. Copyright © 2005 John Wiley & Sons, Ltd.     

Synthesis of biodegradable copolymers with low‐toxicity zirconium compounds. IV. Copolymerization of glycolide with trimethylene carbonate and 2,2‐dimethyltrimethylene carbonate: Microstructure analysis of copolymer chains by high‐resolution nuclear magnetic resonance spectroscopy

The results of the copolymerization of glycolide with cyclic trimethylene carbonate and 2,2‐dimethyltrimethylene carbonate are described. The copolymerization was conducted in the presence of low‐toxicity zirconium(IV) acetylacetonate as an initiator. With this kind of initiator, the composition of the comonomer units in the copolymer chains was assumed to be obtained with high efficiency. Despite significant differences in the comonomer reactivity, in copolymers containing comparable amounts of glycolidyl and carbonate sequences, highly randomized chain structures were observed. This effect resulted from strong intermolecular transesterification that proceeded during the studied copolymerization and caused glycolidyl microblock randomization. The assignment of the spectral NMR lines to appropriate comonomer sequences of polymeric chains was performed in the region of methylene protons of glycolidyl units in ¹H NMR spectra of the copolymers and in the carbonyl region of carbon spectra. The equations were formulated for a detailed characterization of the obtained copolymer chains, the average lengths of the blocks, and the transesterification and randomization coefficients. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 98–114, 2006     

Hyperbranched poly (amine‐ester)‐poly (lactide‐co‐glycolide) copolymer and their nanoparticles as paclitaxel delivery system

A new hyperbranched poly (amine‐ester)‐poly (lactide‐co‐glycolide) copolymer (HPAE‐co‐PLGA) was synthesized by ring‐opening polymerization of D , L ‐lactide (DLLA) glycolid and branched poly (amine‐ester) (HPAE‐OHs) with Sn(Oct)₂ as catalyst. The chemical structures of copolymers were determined by FT‐IR, ¹H‐NMR(¹³C NMR), TGA and their molecular weights were determined by gel permeation chromatography (GPC). Paclitaxel‐loaded copolymer nanoparticles were prepared by the nanoprecipitation method. Their physicochemical characteristics, e.g. morphology and nanoparticles size distribution were then evaluated by means of fluorescence spectroscopy, environmental scanning electron microscopy (ESEM), and dynamic light scattering (DLS). Paclitaxel‐loaded nanoparticles assumed a spherical shape and have unimodal size distribution. It was found that the chemical composition of the nanoparticles was a key factor in controlling nanoparticles size, drug‐loading content, and drug release behavior. As the molar ratio of DL ‐lactide/glycolide to HPAE increased, the nanoparticles size and drug‐loading content increased, and the drug release rate decreased. The antitumor activity of the paclitaxel‐loaded HPAE‐co‐PLGA nanoparticles against human liver cancer H7402 cells was evaluated by 3‐(4, 5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT) method. The paclitaxel‐loaded HPAE‐co‐PLGA nanoparticles showed comparable anticancer efficacy with the free drug. Copyright © 2010 John Wiley & Sons, Ltd.     

Lipase‐Catalyzed Transesterification of Polyesters to Ester Copolymers

Lipase‐catalyzed intermolecular transesterification between two different polyesters has been carried out using in toluene. The transesterification of poly(ε‐caprolactone) (PCL) and (1,4‐butylene adipate) took place via catalysis of lipase from Candida antarctica to give an ester copolymer. ¹³C NMR analysis showed that the resulting polymer was not a mixture of the starting polyesters, but a copolymer consisting of both units. The reaction temperature and solvent amount greatly affected the microstructure of the ester copolymer. Under appropriate conditions, the random copolymer was formed. The enzymatic transesterification has been monitored by size exclusion chromatography (SEC) and ¹³C NMR. Ester copolymers were enzymatically obtained from PCL and other poly(α,ω‐alkylene dicarboxylate)s and their microstructure depended on the polyester structure.     

聚β-羟基丁酸酯和聚ε-己内酯的酯交换反应

以辛酸亚锡为催化剂 ,研究了聚 β 羟基丁酸酯 (PHB)与聚ε 己内酯 (PCL)在液相条件下的酯交换反应 .讨论了反应时间 ,反应温度和催化剂浓度对酯交换反应的影响 .采用1 3C NMR ,FTIR ,DSC ,WAXD和TGA等方法对PHB和PCL共聚酯 (PHB co PCL)的结构进行了表征 ,并对其结晶行为、晶体结构和热稳定性进行了研究 .结果表明 ,通过酯交换反应 ,所得到的共聚酯为嵌段共聚物 .提高反应温度和延长反应时间有利于酯交换反应的发生 .随着酯交换量的增加 ,PHB co PCL的结晶行为发生很大的变化 .但是 ,PHB co PCL晶体结构并没有因为PCL链段的引入而发生变化 ,而且它的热稳定性在空气气氛中略有提高     

Poly(caprolactone‐co‐lactide)/perfluoropolyether block copolymers: Synthesis,thermal, and surface characterization

Poly[(caprolactone‐co‐lactide)‐b‐perfluoropolyether‐b‐(caprolactone‐co‐lactide)] copolymers (TXCLLA) were prepared by ring‐opening polymerization of D ,L ‐dilactide (LA2) and caprolactone (CL) in the presence of α,ω‐hydroxy terminated perfluoropolyether (Fomblin Z‐DOL TX) as macroinitiator and tin(II) 2‐ethylexanoate as catalyst. ¹H NMR analysis showed that LA2 is initially incorporated into the copolymer preferentially with respect to CL. A blocky structure of the polyester segment was also indicated by the sequence distribution analysis of the monomeric units. Differential scanning calorimetry analysis showed the compatibility between poly(lactide) (PLA) and poly(caprolactone) (PCL) blocks inside the amorphous phase with glass‐transition temperature values increasing from ?60 to ?15 °C by increasing the PLA content. Copolymers with high average length of CL blocks were semicrystalline with a melting temperature ranging from +35 to +47 °C. Surface analysis showed a high surface activity of TXCLLA copolymers with values of surface tension independent from the PLA/PCL content and very close to those of pure TX. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 3588–3599, 2005     

Synthesis of biodegradable copolymers with low‐toxicity zirconium compounds. V. Multiblock and random copolymers of L‐lactide with trimethylene carbonate obtained in copolymerizations initiated with zirconium(IV) acetylacetonate

Using zirconium(IV) acetylacetonate as an initiator of lactide/trimethylene carbonate copolymerization allowed us to obtain high‐molecular‐weight copolymers with high efficiency. The reactivity ratios of the comonomers were 13.0 for lactide and 0.53 for trimethylene carbonate. Despite the large differences between the values of the reactivity ratios, copolymers with randomized chain structures were obtained. This phenomenon occurred as a result of an intensive intermolecular transesterification process proceeding along with the reaction of copolymer chain growth and modifying its final structure. Conducting the copolymerization at the relatively low temperature of about 110 °C, which minimized the influence of intermolecular transesterification, made it possible to obtain semicrystalline copolymers with multiblock structures. Increasing the temperature of copolymerization up to 180 °C was associated with strong intensification of the transesterification reactions. At this temperature, amorphous copolymers were obtained with identical compositions but highly randomized chain structures. An analysis of the chain microstructures of the obtained copolymers, determining the average length of the blocks, the intermolecular transesterification ratio, and the degree of chain randomization, was conducted by means of NMR spectroscopy. For this purpose, very specific signal assignment in the carbonyl and methylene carbon regions of the ¹³C NMR spectra to appropriate comonomer sequences of polymeric chains was performed. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 3184–3201, 2006     

Copolymerization of glycolide and trimethylene carbonate

The bulk ring‐opening copolymerization of glycolide with trimethylene carbonate was performed under different conditions. The influence of the composition, temperature, reaction time, and catalyst on the chain microstructure was studied by means of ¹H and ¹³C NMR spectroscopy. The final microstructure was found to be highly dependent on the transesterification reactions. The thermal behavior was sensitive to the composition and to the length of the glycolyl microblocks. Differential scanning calorimetry and X‐ray diffraction demonstrated that glycolyl‐rich sequences could give rise to a single crystalline phase, whereas trimethylene carbonyl units were incorporated into the amorphous phase. The synthesis of copolymers from the melt‐state transesterification of polyglycolide and poly(trimethylene carbonate) homopolymer mixtures was also studied. The hydrolytic degradation rate of the copolymers was found to depend on the microstructure and in general was enhanced with the degree of randomness. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 993–1013, 2006     

NMR analysis of the chain microstructure of biodegradable terpolymers with shape memory properties

Terpolymers of lactide, glycolide and trimethylene carbonate initiated on zirconium acetylacetonate (IV) exhibit shape-memory behaviors in the range of body temperature when appropriate monomer composition and characterizing conditions are applied. In this paper, the procedure of characterizing these terpolymers by means of nuclear magnetic resonance spectroscopy is presented. The ¹H and ¹³C NMR spectra allow to characterize the chain microstructure of these polyester-carbonates in spite of overlapping resonance signals due to the possibility of forming different co-monomeric sequences. Detailed assignment was given for spectral lines in proton and carbon spectra recorded in polar and non-polar deuterated solvents. For quantitative analysis, equations for calculations of average block lengths, long and mixed glycolidyl, lactidyl and carbonate blocks as well as formulas allowing to investigate intramolecular transestrification processes were elaborated.     

Novel synthesis of biodegradable linear and star block copolymers based on ε‐caprolactone and lactides using potassium‐based catalyst

Biodegradable, triblock poly(lactide)‐block‐poly(ε‐caprolactone)‐block‐poly(lactide) (PLA‐b‐PCL‐b‐PLA) copolymers and 3‐star‐(PCL‐b‐PLA) block copolymers were synthesized by ring opening polymerization of lactides in the presence of poly(ε‐caprolactone) diol or 3‐star‐poly(ε‐caprolactone) triol as macroinitiator and potassium hexamethyldisilazide as a catalyst. Polymerizations were carried out in toluene at room temperature to yield monomodal polymers of controlled molecular weight. The chemical structure of the copolymers was investigated by ¹H and ¹³C‐NMR. The formation of block copolymers was confirmed by NMR and DSC investigations. The effects of copolymer composition and molecular structure on the physical properties were investigated by GPC and DSC. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 5363–5370, 2008     

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

Diblock copolymers consisting of methoxy poly(ethylene glycol) (MPEG) and poly(?‐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 ?‐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     

Cationic copolymerization of ε‐caprolactone and L,L‐lactide by an activated monomer mechanism

The cationic homopolymerization and copolymerization of L,L ‐lactide and ε‐caprolactone in the presence of alcohol have been studied. The rate of homopolymerization of ε‐caprolactone is slightly higher than that of L,L ‐lactide. In the copolymerization, the reverse order of reactivities has been observed, and L,L ‐lactide is preferentially incorporated into the copolymer. Both the homopolymerization and copolymerization proceed by an activated monomer mechanism, and the molecular weights and dispersities are controlled {number‐average degree of polymerization = ([M]₀ ? [M]_t)/[I]₀, where [M]₀ is the initial monomer concentration, [M]_t is the monomer concentration at time t, and [I]₀ is the initial initiator concentration; weight‐average molecular weight/number‐average molecular weight ～1.1–1.3}. An analysis of ¹³C NMR spectra of the copolymers indicates that transesterification is slow in comparison with propagation, and the microstructure of the copolymers is governed by the relative reactivity of the comonomers. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 7071–7081, 2006     

Sequence analysis of glycolide and p‐dioxanone copolymers

Low and medium molecular weight copolymers constituted by glycolide and p‐dioxanone units have been synthesized by a ring‐opening polymerization. The p‐dioxanone monomer was obtained from (2‐hydroxyethoxy)acetate or by thermal depolymerization of poly(p‐dioxanone). ¹H and ¹³C NMR spectra were highly sensitive to the chemical sequences, which were effectively assigned by considering the data from samples with different compositions, and the acquisition of heteronuclear ¹H and ¹³C NMR‐correlated spectra. End groups were also identified, allowing methylene protons of sequences involving up to two glycolide units to be distinguished. These data seem basic to analyze degradation products or the influence of thermal treatments in chain microstructure. Glycolide/p‐dioxanone copolymers are an interesting system because changes on chemical sequences can easily occur due to a depolymerization reaction that eliminates p‐dioxanone residues. Furthermore, depending on the polymerization conditions, the occurrence of transesterification reactions may be highly significant. These reactions have a great impact in properties such as the melting temperature and can be easily quantified by NMR spectroscopy because of the occurrence of a new chemical sequence. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2009     

About formation of cycles in Sn(II) octanoate‐catalyzed polymerizations of lactides

At first, formation of cycles in commercial poly(l ‐lactide)s is discussed and compared with benzyl alcohol‐initiated polymerizations performed in this work. This comparison was extended to polymerizations initiated with 4‐cyanophenol and pentafluorothiophenol which yielded cyclic polylactides via end‐biting. The initiator/catalyst ratio and the acidity of the initiator were found to be decisive for the extent of cyclization. Further polymerizations of l ‐lactide were performed with various diphenols as initiators/co‐catalysts. With most diphenols, cyclic polylactides were the main reaction products. Yet, only catechols yielded even‐numbered cycles as main reaction products, a result which proves that their combination with SnOct₂ catalyzed a ring‐expansion polymerization (REP). The influence of temperature, time, co‐catalyst, and catalyst concentrations was studied. Four different transesterification reactions yielding cycles were identified. For the cyclic poly(l ‐lactide)s weight average molecular weights (M_w's) up to 120,000 were obtained, but ¹H NMR end group analyses indicated that the extent of cyclization was slightly below 100%. The influence of various parameters like structure of initiator and catalyst and temperature on the formation of cyclic poly(l ‐lactide)s has been investigated. Depending on the chosen conditions, the course of the polymerization can be varied from a process yielding exclusively linear polylactides to mainly cyclic polylactides. Three different reaction pathways for cyclization reactions have been identified. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018 , 56, 1915–1925