Effects of molecular weight and small amounts of d-lactide units on hydrolytic degradation of poly(l-lactic acid)s

Films of poly(l-lactic acid) (PLLA) with different number-average molecular weights (M_n) and d-lactide unit contents (X_d) were made amorphous and the effects of molecular weight and small amounts of d-lactide units on the hydrolytic degradation behavior in phosphate-buffered solution at 37 °C of PLLA were investigated. The degraded films were investigated using gravimetry, gel permeation chromatography, polarimetry, differential scanning calorimetry, X-ray diffractometry, and tensile testing. To exclude the effects of crystallinity on the hydrolytic degradation, the films were made amorphous by melt-quenching. The incorporation of small amounts of d-lactide units drastically enhanced the hydrolytic degradation of PLLA. In the period of 0-32 weeks, the hydrolytic degradation rate constant (k) of PLLA films increased with increasing X_d, while the k values did not depend on M_n. This means that the effects of X_d on the hydrolytic degradation rate of the films are higher than those of M_n. In contrast, in the period of 32-60 weeks neither X_d nor M_n was a crucial parameter to determine k values, probably because in addition to these parameters the differences in the amount of catalytic oligomers accumulated in films and crystallinity affect the hydrolytic degradation behavior of the films. The initially amorphous PLLA films remained amorphous even after the hydrolytic degradation for 60 weeks.     

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.     

Synthesis, characterization and biodegradation of butanediamine-grafted poly(dl-lactic acid)

Novel butanediamine-grafted poly(dl-lactic acid) polymers (BDPLAs) were synthesized via a series of chemical bulk modifications in this study. Briefly, maleic anhydride (MAH) was first grafted onto the side chain of poly(dl-lactic acid) (PDLLA) molecules via melt free radical copolymerization using benzoyl peroxide (BPO) as initiator to get maleic anhydride-grafted PDLLA polymers (MPLAs); thereafter butanediamine (BDA) was immobilized onto grafted anhydride groups in MPLAs via N-acylation reaction to obtain the desired BDPLAs. Gel permeation chromatography with multi-angle laser light scattering (GPC-MALLS), FT-IR, ¹³C NMR and XPS were employed to qualitatively characterize these synthesized polymers. Rhodamine-carboxyl interaction method and ninhydrin reaction were further used to quantitatively determine the graft ratio of MAH (MAH%) in MPLAs and the graft ratio of BDA (BDA%) in BDPLAs, respectively. The degradations of BDPLAs, PDLLA and MPLAs were investigated by observation of the changes of the pH value of incubation medium, molecular weight and weight loss ratio for a time interval of 12 weeks in vitro, respectively. The results revealed that grafting butanediamine onto PDLLA has weakened or neutralized the acidity of PDLLA degradation products. A uniform degradation of BDPLAs was observed in comparison with an acidity-induced auto-accelerating degradation featured by PDLLA and MPLAs. The biodegradation behaviors of BDPLAs are tunable by controlling the content of BDA. BDPLAs might be a new derivative of PDLLA-based biodegradable materials for medical applications without acidity-caused irritations and acidity-induced auto-accelerating degradation behavior as that of PDLLA.     

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.     

Surface properties and enzymatic degradation of end-capped poly(l-lactide)

Surface properties and enzymatic degradation of poly(l-lactide) (PLLA) end-capped with hydrophobic dodecyl and dodecanoyl groups were investigated by means of advancing contact angle (θ_a) measurement, quartz crystal microbalance (QCM) and atomic force microscopy (AFM). The θ_a values of end-capped PLLA films were larger than those of non-end-capped PLLA films, suggesting that the hydrophobic dodecyl and dodecanoyl groups were segregated on the film surface. The weight changes of end-capped PLLA thin films during enzymatic degradation in the presence of proteinase K were monitored by using a QCM technique. The relatively fast weight loss of PLLA film occurred during first few hours of degradation, followed by a decrease in the erosion rate. The erosion rate of PLLA films at the initial stage of degradation was dependent on the chain-end structure of PLLA molecules, and the value decreased with an increase in the amount of hydrophobic functional groups. The surface morphologies of PLLA thin films before and after degradation were characterized by AFM. After the enzymatic degradation, the surface of non-end-capped PLLA films was blemished homogeneously. In contrast, the end-capped PLLA thin films were degraded heterogeneously by the enzyme, and many hollows were formed on the film surface. From these results, it has been concluded that the introduction of hydrophobic functional groups at the chain-ends of PLLA molecules depressed the erosion rate at the initial stage of enzymatic degradation.     

Influence of cellulose nanowhiskers on the hydrolytic degradation behavior of poly(d,l-lactide)

This paper reports the preparation of bionanocomposites based on poly(d,l-lactide) and cellulose nanowhiskers (PDLLA/CNWs) and studies the influence of the CNWs on the hydrolytic degradation behavior of the polylactide. The hydrolytic degradation process was studied in a phosphate buffer medium through the sample weight loss and also by FTIR, DSC and TGA measurements. The presence of CNWs induced a strong delay in the hydrolytic degradation of the PDLLA, even when the concentration of the nanofillers was only 1%. This effect was related to the physical barrier created by the highly crystalline CNWs that inhibited water absorption and hence retarded the hydrolytic degradation of the bionanocomposites. In addition, the incorporation of cellulose nanocrystals in the PDLLA also made the biopolymer more thermally stable, increasing the initial temperature of mass loss even after the degradation in phosphate medium. The results presented here show the possibility of controlling the biodegradability and prolonging the service life of a polylactide through the incorporation of a small quantity of nanofillers obtained from renewable materials.     

Improved hydrolytic stability of poly(dl-lactide) with epoxidized soybean oil

The multi-arm star polymer (ESOPLA) was obtained by ring-opening polymerization of dl-lactide using multifunctional epoxidized soybean oil (ESO) as an initiator in the presence of a stannous actuate (SnOct₂) catalyst. Gel permeation chromatography with multi-angle laser light scattering (GPC-MALLS), FTIR, ¹H NMR, thermal analysis and in vitro degradation were used to qualitatively characterize the synthesized polymers. The results revealed that ESO plays an important role in increasing the molecular weight, polymerization rate and monomer conversion rate. Degradation analysis demonstrated that the decrease in molecular weight and the weight loss ratio of the star-shaped ESOPLA were lower than that of linear poly(dl-lactide) (PDLLA). The surface topography of pre- and post-degradation materials was characterized by scanning electron microscopy (SEM). These SEM images showed that the linear PDLLA films underwent water erosion more readily than the star-shaped polymer films.     

Swelling and hydrolytic degradation of poly(d,l-lactic acid) in aqueous solutions

Low molecular weight poly(lactic acid) was synthesized by direct polycondensation of lactic acid. The oligomers were characterized by viscometry, light scattering, and gel permeation chromatography (GPC). The swelling behaviour of tablets made of the above polymer immersed in buffer solutions at 37 °C was studied. In the same experiments, the hydrolytic stability of d,l-PLA was assessed by measuring the weight loss after drying the tablets. In order to inhibit any degradation due to bacteria, formaldehyde was added in the solution as biostatic factor. The effect of an incorporated drug on the swelling behaviour of d,l-PLA tablets was also considered. It was found that the incorporation of drug in d,l-PLA tablets increases their swelling index, probably due to the creation of additional porosity in the specimens or other interaction between drug and polymeric matrix.     

Efficient synthesis of new N-alkyl-d-ribono-1,5-lactams from d-ribono-1,4-lactone

d-Ribono-1,4-lactone was treated with ethylamine in DMF to afford N-ethyl-d-ribonamide 9a in quantitative yield. Bromination of amide 9a by the system SOBr₂ in DMF or PPh₃/CBr₄ in pyridine led, after acetylation, to epoxide 7. However, treatment of amide 9a with acetyl bromide in dioxane followed by acetylation gave 2,3,4-tri-O-acetyl-5-bromo-5-deoxyl-N-ethyl-d-ribonamide 10a. Methanolysis of 10a, with sodium methoxide, afforded the N-ethyl-d-ribonolactam 11a in 51% overall yields. Using this method, N-butyl, N-hexyl, N-dodecyl, and N-benzyl-d-ribonolactams 11b-e were obtained in good yields (48-53%).     

Synthesis and characterization of functional l-lactic acid/citric acid oligomer

Oligomers of l-lactic acid and citric acid (PLCA) were synthesized by reacting lactic acid with citric acid in the presence of stannous chloride. The chemical compositions of these multicarboxylated oligomers were verified by FT-IR and ¹H-NMR spectroscopy. The thermal characteristics of the oligomers, such as glass transition temperature T_g, melting temperature T_m and melting enthalpy, were confirmed by DSC. The crystallinity of the oligomers were determined by DSC and WXRD. Meanwhile, the acid-base surface characteristics of PLCA have been determined by contact angle. The results implicated that these oligomers may be used to entrap the cospecies on PLLA surface in tissue engineering.     

Hydrolytic degradation and thermal properties of linear 1-arm and 2-arm poly(dl-lactic acid)s: Effects of coinitiator-induced molecular structural difference

“Linear” 1-arm and 2-arm poly(dl-lactide) [i.e., poly(dl-lactic acid), or PDLLA] polymers with relatively low number-average molecular weights (M_n in the range 0.2-6 × 10⁴ g mol⁻¹) were synthesized using ring-opening polymerization of dl-lactide initiated with tin(II) 2-ethylhexanoate (i.e., stannous octoate) and coinitiators of dl-lactic acid and ethylene glycol (these PDLLA polymers are hereafter abbreviated as 1-DL and 2-DL, respectively). Their glass-transition properties were monitored by differential scanning calorimetry, and their hydrolytic degradation was investigated using gravimetry and gel permeation chromatography. The results of the present study indicate that the coinitiator-induced molecular structural difference of the terminal groups, the chain directional change, the incorporated coinitiator moiety as an impurity in the middle of the molecule, and the molecular weight each affect both the hydrolytic degradation behavior and rate, and the glass-transition properties of the “linear” 1-DLs and 2-DLs. The glass-transition temperature (T_g) values were higher for the 2-DLs than for the 1-DLs, indicating low chain mobility and a strong inter-chain interaction of 2-arm PDLLA. However, the coinitiator-induced molecular structural difference did not produce a difference in the excess free volume of the end groups between the 1-DLs and 2-DLs, despite the difference produced in the terminal groups. On the other hand, although the hydrolytic degradation of the 1-DLs and 2-DLs proceeds via bulk erosion, significant surface erosion also occurs in the 2-DLs. This should have caused a larger weight loss and lower decrease rate of M_n of the 2-DLs compared to those of the 1-DLs. Moreover, the results of the present study indicate that in 2-arm PDLLA selective chain cleavage at the terminal ester groups or second ester groups from the chain terminals, which are induced by two terminal hydroxyl groups, is the significant hydrolytic degradation route. However, the random cleavage of ester groups, irrespective of their position, is the main hydrolytic degradation route.     

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.     

One-pot inversion of d-mannono-1,4-lactone for the practical synthesis of l-ribose

l-Ribose was synthesized in a concise manner from d-mannono-1,4-lactone using one-pot inversion conditions. Treatment of d-mannono-1,4-lactone with piperidine, followed by mesylation-induced S_N2-type O-alkylation, afforded the desired one-pot inversion in an optimum yield, and the following straightforward transformations provided l-ribose in good yields.     

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.     

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.     

Interactions of aluminum(III) with the biologically relevant ligand d-ribose

Aluminum(III) can be absorbed when it is appropriately complexed. There are several plasma components which can bind weakly Al(III). Many proteins bind Al(III) in solution quite strongly. Carbohydrates bearing an abundance of electronegative functional groups can interact with metal cations. In solution, d-ribose exists as a mixture at equilibrium of many isomers and only a few of them bear a ‘complexing’ sequence of the hydroxyl groups. The presence of d-ribose in an Al(III) solution experiences a decrease of its Brönsted-acid sites. The lowering of the Brönsted acidity of an Al(III)-d-ribose mixture suggests the existence of attractive interactions (‘association’) between Al(III) ion and the complexing sequence of the hydroxyls of d-ribose. There is enhancement in the stability of the interaction complexes between Al(III) and d-ribose through strong intramolecular hydrogen bonding, which offers the possibility to investigate the kinetics of the subsequent proton release reactions. On the basis of the kinetic results, it may be concluded that proton release reactions, which are associated with the complexation reactions, are associatively activated. The complexes (Al(H₂O)_6−n(d-ribose_−nH)⁽³⁻ⁿ⁾⁺) resulting from the various ‘complexing’ forms of d-ribose are formed at mainly acidic pH. As the pH increases, the values of the activation enthalpy, ΔH^≠, are changing, because of the formation of mixed hydroxo-complexes (Al(H₂O)_6−n−m(OH)_m(d-ribose_−nH)^(3−n−m)+); finally, OH⁻ displaces d-ribose from the coordination sphere of Al(III) in a rather slow process, i.e. with high values of ΔH^≠; the activation enthalpy values, ΔH^≠, decrease with the progression of the displacement, becoming finally very small due to the formation of a precipitate. Chelate coordination of d-ribose with some divalent and trivalent metal ions has been also reported.     

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.     

Degradation behaviors of electrospun fibrous composites of hydroxyapatite and chemically modified poly(dl-lactide)

It is essential to individually tailor the biodegradability of electrospun fibers and their composites to meet the requirements of specific application. Electrospun poly(dl-lactide) (PDLLA) fibers grafted with functional groups were obtained to induce in situ mineralization of hydroxyapatite (HA), and HA/PDLLA composites were fabricated through hot-pressing of mineralized fibers after layer-by-layer deposition. The degradation behaviors during up to 1 year incubation were clarified for functionalized PDLLA fibers, mineralized HA/PDLLA fibers and hot-pressed composites. The carboxyl and amino groups of electrospun fibers indicated enhancement and alleviation of the autocatalysis effect on the polyester hydrolysis, respectively. The distribution of HA within fiber matrices led quick and strong water absorption, and caused neutralization of the weak acid environment and alleviation of the autocatalysis effect. Due to the location of mineralized HA on the surface of functionalized fibers, significant HA loss and preferential removal of amorphous and low-crystalline apatitic phase were determined during the degradation process. The hot-pressed composites indicated dense structure, small pore size and fusion on the fiber surface, leading significantly lower degradation rate than electrospun fibers and mineralized fibers. Higher degradation rate of matrix polymers and HA loss were shown for hot-pressed composites from mineralized fibers than those from blend electrospun HA/PDLLA fibers. The obtained results should provide solid basis for further applications of functionalized PDLLA fibers, mineralized fibers and fibrous composites in biomedical areas.     

Synthesis and structural study of copolymers of l-lactic acid and bis(2-hydroxyethyl terephthalate)

Poly(ethylene terephthalate)-poly(lactic acid) (PET-PLLA) copolyesters were synthesized by the melt reaction of bis(2-hydroxyethyl terephthalate) (BHET) with l-lactic acid oligomers (OLLA) in the presence of SnCl₂, H₂O-p-toluene sulfonic acid, H₂O catalytic system. The ¹H and ¹³C NMR studies confirm the incorporation of lactate units in PET chains after reaction. Copolyesters containing nearly equimolar terephthalate/lactate ratio are not completely random and present some block-copolymer character, while the microstructure of PET-rich copolyesters is a random one. Due to a longer PET sequence length, the latter exhibit a melting point close to 210 °C while the other ones are amorphous. SEC/MALDI-TOF MS off-line coupling was used to obtain the absolute average molar masses of the copolyesters. The results indicate that the conventional polystyrene calibration method leads to a strong overestimation of PET-PLLA molar masses, while the determined by NMR is much closer to the SEC/MALDI value.