Racemization behavior of l,l-lactide during heating

To control the depolymerization process of poly(l-lactic acid) into l,l-lactide for feedstock recycling, the racemization of l,l-lactide as a post-depolymerization reaction was investigated. In the absence of a catalyst, the conversion to meso-lactide increased with increase in the heating temperature and time at a higher rate than the conversion into oligomers. The resulting high composition of meso-lactide suggests that the direct racemization of l,l-lactide had occurred in addition to the known racemization mechanism that occurs on the oligomer chains. In the presence of MgO, the oligomerization rapidly proceeded to reach an equilibrium state between monomers and oligomers. The equilibrium among l,l-, meso-, and d,d-lactides was found to be a convergent composition ratio l,l-:meso-:d,d-lactides = 1:1.22:0.99 (wt/wt/wt) after 120 min at 300 °C. This composition ratio also indicates that in addition to the known racemization reaction on the oligomer chains, direct racemization among the lactides is also a frequent occurrence.     

Prevailing mechanisms of the hydrolytic degradation of oligo(d,l-lactide)-grafted dextrans

The predominant mechanism of the hydrolytic degradation of oligo(d,l-lactide)-grafted dextrans in phosphate buffer was followed by quantifying both released dextran and lactic acid from the copolymers. The studied amphiphilic copolymers, with well-defined structure, exhibited various oligo(d,l-lactide) weight fractions (F^OLA) while having a quite high extent of free hydroxyl groups (>90%). Depending on their F^OLA, oligo(d,l-lactide)-grafted dextrans were soluble either in water or in organic solvents (THF, toluene, …) and different prevailing mechanisms of hydrolytic degradation were observed. The copolymer soluble in THF, with longer oligo(d,l-lactide) grafts and higher F^OLA, was found to degrade via a particular mechanism by which the greatest part of dextran was released into buffer medium during the first two weeks of degradation. During the initial stage of degradation, the hydrophilicity of dextran backbone was considered to be the main driving force for the hydrolytic cleavage of the ester linkage between backbone and grafts. Released oligo(d,l-lactide) grafts were found to be degraded via chain-end degradation or random degradation depending on their solubility in buffer medium. In case of water-soluble copolymers with shorter oligo(d,l-lactide) grafts and lower F^OLA, the chain-end degradation was exclusively observed.     

Ring-opening polymerization of l-lactide in supercritical carbon dioxide using PDMS based stabilizers

Ring-opening suspension polymerization of l-lactide in supercritical CO₂ (scCO₂) was investigated in the presence of different stabilizer architectures based on poly(dimethyl siloxanes) (PDMS). Two amphiphilic AB type block copolymers, a graft copolymer, and an ester-capped PDMS were selected to find their efficacy as stabilizers for the synthesis of poly(l-lactide) (PLLA) in scCO₂. The stabilizer’s efficiency was analyzed in terms of the molecular weight, yield, and particle morphology of PLLA. The block copolymers, poly(dimethylsiloxane)-b-poly(acrylic acid) (PDMS-b-PAA) and poly(dimethylsiloxane)-b-poly(methacrylic acid) (PDMS-b-PMA) were found to be effective, leading to the formation of fine, discrete PLLA microparticles. On the other hand, the graft copolymer, poly(dimethylsiloxane-g-pyrrolidonecarboxylic acid) (PDMS-g-PCA) and acetylated PDMS (PDMS-OAc) failed to give an enough stabilization to the PLLA due to their short polymer-philic chains, resulting in hard agglomerates.     

Miscibility and hydrolytic degradation in alkaline solution of poly(l-lactide) and poly(p-vinyl phenol) blends

Poly(l-lactide) (PLLA) was melt-blended with poly(p-vinyl phenol) (PVPh) using a two-roll mill, and the miscibility between PLLA and PVPh and degradation of the blend films were investigated. It was found that PLLA/PVPh blend has miscibility in the amorphous state because only single T_g was observed in the DSC and DMA measurements. The T_g of the PLLA/PVPh blend could be controlled in the temperature range from 55 °C to 117 °C by changing the PVPh weight fraction. In alkaline solution, degradation rate of PLLA/PVPh blends was faster than that of neat PLLA because PVPh could dissolve in alkaline solution. The surface morphology of degraded PLLA and PLLA/PVPh blend were observed by SEM. The surface morphology of degraded PLLA/PVPh blend was finer than that of PLLA. Young's modulus of PLLA/PVPh blend increased with increasing PVPh content. Yield stress of PLLA/PVPh blends whose PVPh content was less than 30 wt% kept the level of about 55 MPa and that of PLLA/PVPh blend whose PVPh content was 40 wt% is much lower than that of neat PLLA.     

Accelerated hydrolytic degradation of Poly(l-lactide)/Poly(d-lactide) stereocomplex up to late stage

Poly(l-lactide) (PLLA)/poly(d-lactide) (PDLA) blend specimens containing only stereocomplex as crystalline species, together with those of pure PLLA and PDLA specimens, were prepared by solution crystallization using acetonitrile as the solvent. Their accelerated hydrolytic degradation was carried out in phosphate-buffered solution at elevated temperatures of 70-97 °C up to the late stage. During hydrolytic degradation, the stereocomplex crystalline residues were first traced by gel permeation chromatography. Similar to the hydrolytic degradation of pure PLLA and PDLA specimens, the hydrolytic degradation of stereocomplexed PLLA/PDLA blend specimens slowed down at the late stage when most of the amorphous chains were removed and crystalline resides were formed and degraded. The estimated activation energy for hydrolytic degradation of stereocomplex crystalline residues (97.3 kJ mol⁻¹) is significantly higher than 75.2 kJ mol⁻¹ reported for α-form of PLLA crystalline residues. This indicates that the stereocomplex crystalline residues showed the higher hydrolysis resistance compared to that of α-form of PLLA crystalline residues.     

Kinetics of thermo-oxidative and thermal degradation of poly(d,l-lactide) (PDLLA) at processing temperature

Poly(d,l-lactide) (PDLLA) degraded at processing temperature under air and nitrogen. A random chain scission model was established and used to determine the activation energy E_a, and FT-IR, ¹H and ¹³C NMR were used to elucidate the degradation behavior under different atmospheres. Results showed that there were two to three stages. The 1st stage was dominated by the oligomers containing carboxylic acid groups and hydroxyl groups, during which oxygen and nitrogen had little effect on the degradation, thus they share similar E_a. When the oligomers were consumed over or evaporated, the 2nd stage began, and oxygen had a promoting effect on the thermo-oxidation process, resulting in the great decrease in E_a. The third stage of PDLLA was observed when it degraded under nitrogen over 200 °C, which was caused by the appearance of carboxylic acid substance.     

New Sn(IV) and Ti(IV) bis(trimethylsilyl)amides in d,l-lactide polymerization, SEM characterization of polymers

Ring-opening polymerization of d,l-lactide initiated with new chlorotris(bis(trimethylsilyl) amido) tin(IV), tetrakis(bis(trimethylsilyl)amido) tin(IV) and titanium(IV) was investigated. New complexes reveal practically quantitative conversion degrees and produced polymers with higher molecular weight with respect to reference alkoxo-species.The X-ray crystal structure of chlorotris(bis(trimethylsilyl)amido) tin (IV) was investigated. Axial enantiomerism of [SnCl{N(SiMe₃)₂}₃] molecules in solution was studied by high-field dynamic NMR, the value of Gibbs activation energy ΔG^‡ = 59.5 kJ/mol.Field emission SEM investigation of bulk polymer samples and thin films on conductive Al foil revealed a stratified fibrous textures in the bulk polymers, as well as nanoscaled topographical features due to coils and entanglements of individual macromolecules in thin films.     

Synthesis and micelle formation of triblock copolymers of poly(methyl methacrylate)-b-poly(ethylene oxide)-b-poly(methyl methacrylate) in aqueous solution

Amphiphilic triblock copolymers of poly(methyl methacrylate)-b-poly(ethylene oxide)-b-poly(methyl methacrylate) (PMMA-b-PEO-b-PMMA) with well-defined structure were synthesized via atom transfer radical polymerization (ATRP) of methyl methacrylate (MMA) initiated by the PEO macroinitiator. The macroinitiator and triblock copolymer with different PMMA and/or PEO block lengths were characterized with ¹H and ¹³C NMR and gel permeation chromatography (GPC). The micelle formed by these triblock copolymers in aqueous solutions was detected by fluorescence excitation and emission spectra of pyrene probe. The critical micelle concentration (CMC) ranged from 0.0019 to 0.016 mg/mL and increased with increasing PMMA block length, while the PEO block length had less effect on the CMC. The partition constant K_v for pyrene in the micelle and in aqueous solution was about 10⁵. The triblock copolymer appeared to form the micelles with hydrophobic PMMA core and hydrophilic PEO loop chain corona. The hydrodynamic radius R_h,app of the micelle measured with dynamic light scattering (DLS) ranged from 17.3 to 24.0 nm and increased with increasing PEO block length to form thicker corona. The spherical shape of the micelle of the triblock copolymers was observed with an atomic force microscope (AFM). Increasing hydrophobic PMMA block length effectively promoted the micelle formation in aqueous solutions, but the micelles were stable even only with short PMMA blocks.     

Evaluation of kinetics parameters for poly(l-lactic acid) hydrolysis under high-pressure steam

In order to evaluate more precise kinetics parameters: rate constant k and E_a values for poly(l-lactic acid) hydrolysis, the reaction was carried out under high-pressure steam in a temperature range of 100-130 °C. Molecular weights of hydrolyzates were calculated by the universal calibration method without being influenced by any weight loss. The changes in molecular weight could be successfully explained according to the auto-catalytic hydrolysis mechanism, clearly indicating the critical point. Resulting k and E_a values were estimated as 8.4 × 10⁻⁵-7.2 × 10⁻⁴ s⁻¹ and 87.2 kJ mol⁻¹ with high R² values, respectively. Moreover, to determine the deviation of the parameter values, influences of four factors on the measurements and calculation: (1) use of number-average molecular weight value alone, (2) use of relative molecular weight based on polystyrene standards, (3) weight loss during the hydrolysis, and (4) selection of reaction mechanism were evaluated quantitatively.     

Investigation of the degradation behaviour of poly(ethylene glycol-co-d,l-lactide) copolymer

The aim was to investigate the degradation behaviour of poly(ethylene glycol-co-d,l-lactide) (PEG-d,l-PLA) multiblock copolymer, in bulk and as microspheres, in aqueous medium. The degradation behaviour of PLA homopolymers in bulk and microspheres was evaluated as comparison.Microsphere preparation was performed by the double emulsion solvent evaporation method. Physical-chemical characterization of the raw polymers and the microspheres was performed by nuclear magnetic resonance (NMR) and modulated differential scanning calorimetry (MDSC). Polymer molecular weight, before and after incubation in aqueous environment, was evaluated by GPC; water uptake and mass loss were determined gravimetrically.The presence of PEG segments inside PLA chains gave a characteristic spongy structure to the microspheres. A significant increase in polymer T_g values was found for the microsphere formulations compared to polymer in bulk. After 63 days of incubation in the aqueous environment, the PEG-d,l-PLA microspheres achieved an average M_w reduction of 47% compared to 20% for PLA microspheres. The corresponding M_w decrease of the polymers in bulk was significantly higher: 72% and 41% for PEG-d,l-PLA and PLA, respectively.The data show how the degradation behaviour of polymer in bulk in an aqueous environment is significantly different from the behaviour of the corresponding microspheres. These results highlight the importance of performing a thorough physical-chemical characterization on microsphere formulations.     

Ring-opening polymerization of l-lactide by organotin(IV)alkoxides,R2Sn(OPr)2: Estimation of the activation parameters

The ring-opening polymerization of l-lactide, l-LA, to give poly-l-lactide by R₂Sn(OPrⁱ)₂ compounds, where R = Buⁿ and p-XC₆H₄ (X = CF₃, F, H, Me and OMe) has been studied in benzene over a temperature range. There is a relatively small variation in ΔH^≠ as a function of R with all the values falling within the range 11 ± 2 kcal mol⁻¹. The entropy of activation, ΔS^≠, is consistently large and negative, −50 ± 5 eu, supporting the view that the ring-opening event, the enchainment step involves a highly ordered transition state. The crystal and molecular structures of the compounds Ph₂Sn(OPrⁱ)₂, (p-FC₆H₄)₂Sn(OPrⁱ)₂ and (p-Me₂NC₆H₄)₃SnOPrⁱ are also reported. While the latter compound is monomeric in the solid state the former are both dimeric with a pair of bridging OPrⁱ ligands.     

Hydrolytic and enzymatic degradation of poly(trimethylene carbonate-co-d,l-lactide) random copolymers with shape memory behavior

A series of homo- and copolymers were synthesized by ring-opening polymerization of 1,3-trimethylene carbonate and d,l-lactide, using low toxic Zn(Lac)₂ as catalyst. The hydrolytic and enzymatic degradation of PTMC homopolymer and PTDLA copolymers was performed at 37 °C in pH 7.4 phosphate buffered saline or in pH 8.5 Tris buffer using proteinase K. Degradation was followed by using various analytical techniques such as NMR, GPC, DSC and ESEM. PTMC degrades extremely slowly by pure hydrolysis or in the presence of proteinase K. In contrast, PTDLA copolymers with different compositions degrade at various rates both in PBS and in enzyme solutions. The higher the LA content, the faster the degradation. LA units are preferentially degraded during hydrolytic degradation, indicating that ester bonds are more susceptible to hydrolytic cleavage than carbonate ones. Changes in surface morphology are observed during enzymatic degradation, in agreement with surface erosion process. The PTDLA11 copolymer with equivalent TMC/LA contents is highly elastic. Its residual strain is approximately 4% after the first cycle at a strain of 50%. The shape recovery ratio is up to 83%. Therefore, it is concluded that high molecular weight PTDLA copolymers are promising candidates for clinical applications in minimally invasive surgery.     

Influence of hydrolytic degradation on the surface properties of poly-5d/95l-lactide resorbable bone plates

This study explores in vitro aging effects on the surface properties of resorbable PLA95 (poly-5d/95l-lactide) bone plates. The in vitro degradation of injection molded PLA95 bone plates was undertaken by soaking them in a PBS solution. Specimens were harvested at 0, 4, 6, 8, 12, 20, and 26 weeks. After each in vitro aging period, the surface morphology, viscosity, chemical structure, wettability, and thermal properties of the PLA95 bone plates were examined by scanning electron microscopy (SEM), capillary viscometers, attenuated total reflection fourier transform infrared spectroscopy (ATR-FTIR), contact angle, and modulated differential scanning calorimetry (MDSC), respectively. The surface morphology of aged PLA95 bone plates exhibited bulk erosion. As hydrolysis progressed, the inherent viscosity (I.V.) of the PLA95 plates gradually decreased from 0.83 ± 0.01 dL/g at week 0-0.46 ± 0.03 dL/g at week 26. However, the absorbance peak intensity ratio between δ_{as CH3} (A_1452 cm⁻¹) and ν_CO (A_1750 cm⁻¹) and the contact angle reveal different tendencies than that of molecular weight, which decreases. The contact angle of the PLA95 plates decreased until week 4, increased until week 8, and subsequently decreased again. Peak separation analysis reveals that the equilibrium part of the modulated DSC overlapped curves exhibit triple endothermic peaks. Over time, in vitro degradation changes the position and area of the individual peaks. After different time periods of degradation, the variation of wettability shows a tendency similar to the change of PLA95 plates crystallinity; the intensity ratio of A_1452 cm⁻¹ and A_1750 cm⁻¹ (δ_{as CH3}/ν _CO) absorbance peaks varied like the ratio of β/α-crystal heat of fusion. Results also show a similarity in the degradation time dependence in MDSC, contact angle, and ATR-FTIR measurements. During the in vitro aging process, the breakdown and subsequent recrystallization of PLA95 molecular chains might be attributed to a progressive change in wettability and the molecular conformation between δ_{as CH3} and ν_CO.     

Study of amphiphilic poly(1-dodecene-co-para-methylstyrene)-graft-poly(ethylene glycol). Part II: Preparation and micellization behavior of the amphiphilic copolymers

Poly(1-dodecene-co-pMS) copolymers were brominated by HBr/H₂O₂ system with high selectivity at the methyl groups of pMS units. It was found that longer reaction time, higher pMS content, and lower molecular weight of the copolymers were helpful for higher degree of bromination. Through a modified Williamson ether synthesis, poly(ethylene glycol) monomethyl ethers (PEG) were grafted onto the brominated copolymers, and the amphiphilic poly(1-dodecene-co-pMS)-graft-PEG copolymers which can be readily dissolved in n-octane were successfully synthesized. Due to their amphiphilic characteristics, they can self-assemble spontaneously into reverse micelles in n-octane. Their micellization behaviors were investigated by fluorescence probe technique, transmission electron microscopy (TEM), and dynamic light scattering (DLS). The critical micelle concentrations of the three copolymers in n-octane were determined at about 1.26 × 10⁻⁴, 1.58 × 10⁻⁴, and 1.95 × 10⁻⁴ g ml⁻¹ by fluorescence measurements. The morphologies of micelles were preliminarily explored by TEM and were found to be spheres.     

Intermolecular/interionic interactions in l-leucine-, l-asparagine-, and glycylglycine-aqueous electrolyte systems

Ultrasonic velocity and density values have been measured for ternary systems (amino acid/di-peptide + salt + water): l-leucine/l-asparagine/glycylglycine each in 1.5 M aqueous solutions of NaCl or NaNO₃ or KNO₃ used as solvents for several concentrations of amino acids/di-peptide at different temperatures in the range of 298.15-323.15 K. The ultrasonic velocity values have been found to increase with increase in amino acids/di-peptide concentration and temperature in all the systems. The increase in ultrasonic velocity with increase in concentration has been discussed in terms of electrostatic interactions occurring between terminal groups of zwitterions (NH₄⁺ and COO⁻) and Na⁺, K⁺, Cl⁻, NO₃⁻ ions. The interactions of water dipoles with cations/anions and with zwitterions have also been taken into consideration. It has been observed that the ion-zwitterion and ion-dipole attractive forces are stronger than those of ion-hydrophobic repulsive forces. These interactions comprehensively introduce the cohesion into solutions under investigation. The cohesive forces are further enhanced on successive increases in solute concentration. Using ultrasonic velocity and density data, the parameters such as isentropic compressibility (κ_s), change (Δκ_s) and relative change (Δκ_s/κ₀) in isentropic compressibility, specific acoustic impedance (Z) and relative association (RA) have been computed. The isentropic compressibility values decrease with increase in the concentration of solutes as well as with temperature. The decrease in κ_s values with increase in concentration of l-leucine, l-asparagine and glycylglycine in 1.5 M aqueous solutions of NaCl, NaNO₃ and KNO₃ have been explained in terms of an increase in the number of incompressible molecules/zwitterions in solutions and the formation of compact zwitterions-water dipole and zwitterions-ions structures in solutions. The decrease in κ_s values with increase in temperature has been attributed to the corresponding decrease of κ_relax. (relaxational part of compressibility)_, which is dominant over the corresponding increase of κ_∞ (instantaneous part of compressibility). The trends of variations of Δκ_s, Δκ_s/κ₀, Z and RA with change of concentration and temperature have also been interpreted in terms of various intermolecular/interionic interactions existing in the systems.     

Self-accelerated biodegradation of electrospun poly(ethylene glycol)-poly(l-lactide) membranes by loading proteinase K

Proteinase K was successfully loaded inside ultrafine fibers of poly(ethylene glycol)-poly(l-lactide) (PELA) by emulsion electrospinning. A core/shell fiber structure was formed and verified by a transmission electron microscope. In vitro biodegradation of electrospun PELA membranes containing proteinase K (PELA-P) was examined in Tris-HCl buffer solution at pH 8.6 and 37 °C in comparison with electrospun PELA membranes without proteinase K. During biodegradation, mass loss, water absorption, pH value of the incubated buffer, fibrous morphology and thermal properties were monitored. Results suggested that PELA-P membranes degraded significantly faster than PELA membranes. A significant drop in pH value of the buffer after incubation of PELA-P membranes for 1 d was observed, and after 7 d, PELA-P membranes lost their fibrous appearance and masses almost completely. In contrast, electrospun PELA membranes did not show any obvious changes. The obtained electrospun PELA-P membranes exhibited self-accelerated biodegradability and could benefit drug controlled release and tissue regeneration.     

Electrospun poly(l-lactide)-grafted hydroxyapatite/poly(l-lactide) nanocomposite fibers

Composite fibers composed of poly(l-lactide)-grafted hydroxyapatite (PLA-g-HAP) nanoparticles and polylactide (PLA) matrix were prepared by electro-spinning. Environmental scanning electron microscope (ESEM) and transmission electron microscopy (TEM) were employed to investigate the morphology of the composite fibers and the distribution of PLA-g-HAP nanoparticles in the fibers, respectively. At a low content (∼4 wt%) of PLA-g-HAP, the nanoparticles dispersed uniformly in the fibers and the composite fibrous mats exhibited higher strength properties, compared with the pristine PLA fiber mats and the simple hydroxyapatite/PLA blend fiber mats. But when the content of PLA-g-HAP further increased, the nanoparticles began to aggregate, which resulted in the deterioration of the mechanical properties of the composite fiber mats. The degradation behaviors of the composite fiber mats were closely related to the content of PLA-g-HAP. At a low PLA-g-HAP content, degradation may be delayed due to the reduction of autocatalytic degradation of PLA. When PLA-g-HAP content was high, degradation rate increased because of the enhanced wettability of the composite fibers and the escape of the nanoparticles from fiber surfaces during incubation.     

Synthesis and characterization of particles consisting of a biodegradable poly(l-lactide) core and a functional hydrophilic shell

Block copolymers consisting of poly(solketal acrylate) and poly(l-lactide) were synthesized by combination of atom transfer radical polymerization (ATRP) and ring opening polymerization (ROP) technique. Block copolymerization has been done by two different pathways, simultaneously and sequentially by using a dual functional initiator. Well defined block copolymers were obtained by sequential block copolymerization first implementing ROP of l-lactide followed by ATRP of solketal acrylate. After hydrolysis of the solketal acrylate segments hydrophilic poly(2,3-dihydroxypropyl acrylate) blocks were obtained. The amphiphilic block copolymers were able to self-organize in aqueous solution. Aggregation behavior was studied by means of dynamic and static light scattering. Time dependent enzymatic and hydrolytic degradation of the poly(l-lactide) cores was detected by dynamic light scattering. If enzymatic solutions were used the degradation process proceeded faster and was completed within 4000 min.     

Thermodynamic properties of hydrated sodium l-threonate Na(C4H7O5)·H2O(s)

Low-temperature heat capacities of the compound Na(C₄H₇O₅)·H₂O(s) have been measured with an automated adiabatic calorimeter. A solid-solid phase transition and dehydration occur at 290-318 K and 367-373 K, respectively. The enthalpy and entropy of the solid-solid transition are Δ_transH_m = (5.75 ± 0.01) kJ mol⁻¹ and Δ_transS_m = (18.47 ± 0.02) J K⁻¹ mol⁻¹. The enthalpy and entropy of the dehydration are Δ_dH_m = (15.35 ± 0.03) kJ mol⁻¹ and Δ_dS_m = (41.35 ± 0.08) J K⁻¹ mol⁻¹. Experimental values of heat capacities for the solids (I and II) and the solid-liquid mixture (III) have been fitted to polynomial equations.     

Intermolecular/interionic interactions in l-isoleucine-, l-proline-, and l-glutamine-aqueous electrolyte systems

Speed of sound and density values for ternary systems (amino acid + salt + water): l-isoleucine/l-proline/l-glutamine in aqueous solutions of 1.5 M KCl, 1 M KNO₃, and 0.5 M K₂SO₄ have been measured for several concentrations of amino acids at different temperatures (303.15, 308.15, 313.15, 318.15, and 323.15 K). Using speed of sound and density data, the thermodynamic parameters such as isentropic compressibility (κ_s), change in isentropic compressibility (Δκ_s) and relative change (Δκ_s/κ₀) in isentropic compressibility have been computed. The isentropic compressibility values decrease with increase in the amino acid concentration as well as with temperature. The decrease in κ_s values with increase in concentration of l-isoleucine/l-proline/l-glutamine in 1.5 M KCl, 1 M KNO₃, and 0.5 M K₂SO₄ has been ascribed to an increase in the number of incompressible zwitterions in solutions, and the formation of ‘zwitterions-ions’ and ‘zwitterions-water dipole’ entities in solutions. The decrease in κ_s values with increase in temperature has been attributed to the corresponding decrease of κ_relax (a relaxational part of compressibility), which is dominant over the corresponding increase of κ_∞ (an instantaneous part of compressibility). The trends of variation of Δκ_s and Δκ_s/κ₀ with variations in solute concentration and temperature have also been discussed in terms of solute-solute and solute-solvent intermolecular/interionic interactions operative in the systems.