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.     

Improvement of mechanical properties of poly(dl-lactide) films by blending of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate)

Poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) and poly(dl-lactide) (PDLLA) were blended at different ratios in an attempt to form a biomaterial with suitable properties for nerve regeneration. FT-IR and X-ray analysis showed that the blending of the PDLLA component did not alter the helical structure of PHBHHx, but did lead to a reduction of crystallinity. Differential scanning calorimetry (DSC) analysis indicated that the two polymers were immiscible in the melted state. The mechanical properties of certain composite films were more desirable than those of unblended PDLLA films. Blends consisting of PDLLA and PHBHHx at ratios of 2:1 and 1:2 exhibited a lower elastic modulus and a higher elongation at break compared to unblended PDLLA. ELISA results indicated that the amount of fibronectin adsorbed on composite films was much higher than the amount adsorbed on PDLLA film. The results of this study demonstrate the feasibility of using PDLLA/PHBHHx blended materials for biomedical applications.     

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.     

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.     

DSC analysis of isothermal melt-crystallization, glass transition and melting behavior of poly(l-lactide) with different molecular weights

Isothermal melt-crystallization, glass transition and melting behavior of poly(l-lactide) (PLLA) with different molecular weights were investigated by using differential scanning calorimetry. Analysis by Avrami equation showed that crystallization was initiated by heterogeneous nucleation, followed by 3-dimensional growth. The maximum reciprocal half-time of crystallization (1/t_1/2) was detected at 105 °C. Double endothermic peaks were observed around the glass transition for PLLA with intermediate crystallinities, indicating the coexistence of bulk-like and confined amorphous regions. Double-melting behavior was analyzed and combined with the equilibrium melting temperature evaluation by non-linear Hoffman-Weeks extrapolation, from which a value of 207.6 °C was deduced for PLLA of infinite molecular weight. Lauritzen-Hoffman theory was employed to analyze the crystallization kinetics. Regime II-III transition was found to occur at 120 °C for PLLA of lower molecular weight. The crystal morphology was also examined by scanning electron microscopy through chemical etching method.     

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.     

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.     

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.     

Effect of type of peroxide on cross-linking of poly(l-lactide)

Poly(l-lactide) (PLLA) was cross-linked with various types of peroxides under constant mole ratios of peroxide-derived radicals to PLLA during reactive extrusion. Peroxides were classified into three groups according to their decomposition rates (Group I: fast, Group II: moderate and Group III: slow) and comparisons were performed within each group. Cross-linking behavior was readily understood in terms of free radical efficiency and hydrogen abstraction ability of radicals. In the case of Groups II and III, the weight-average molecular weight (M_w) of cross-linked PLLA increased with overall hydrogen abstraction ability, because slow decomposition caused uniform cross-linking in molten PLLA. In Group I, M_w and gel fraction were higher than other groups despite Group I's lower hydrogen abstraction ability, leading to the conclusion that peroxide decomposition localized in solid PLLA caused partial cross-linking because of rapid decomposition. Furthermore, the efficiency of peroxide-induced cross-linking was investigated using the Charlesby-Pinner equation.     

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.     

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.     

Preparation and characterization of biodegradable poly(l-lactide)/chitosan blends

In order to improve the properties of chitosan and obtain new fully biodegradable materials, blends of poly(l-lactide) (PLLA) and chitosan with different compositions were prepared by precipitating out PLLA/chitosan from acetic acid-DMSO mixtures with acetone. The blends were characterized by Fourier transform infrared analysis (FTIR), X-ray photoelectron spectroscopy (XPS), differential scanning calorimetry (DSC), ¹³C solid-state NMR and Wide-angle X-ray diffraction (WAXD). FTIR and XPS results showed that intermolecular hydrogen bonds existed between two components in the blends, and the hydrogen bonds were mainly between carbonyls of PLLA and amino groups of chitosan. The melting temperatures, cold crystallization temperatures and crystallinity of the PLLA component decreased with the increase in chitosan content. Blending chitosan with PLLA suppressed the crystallization of the PLLA component. Although the crystal structure of PLLA component was not changed, the crystallization of the blends was affected because of the existence of hydrogen bonds between two components, which was proved by WAXD results.     

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.     

Crystallization behavior of poly(l-lactic acid)

This article contains a detailed analysis of the crystallization behavior of poly(l-lactic acid) (PLLA). Crystallization rates of PLLA have been measured in a wide temperature range, using both isothermal and non-isothermal methods. The combined usage of multiple thermal treatments allowed to obtain information on crystallization kinetics of PLLA at temperatures almost ranging from glass transition to melting point. Crystallization rate of PLLA is very high at temperatures between 100 and 118 °C, showing a clear deviation from the usual bell-shaped curve. This discontinuity has been ascribed to a sudden acceleration in spherulite growth, and is not associated to morphological changes in the appearance of PLLA spherulites. Experimental data of spherulite growth rates of PLLA have been analyzed with Hoffman-Lauritzen method. Applicability and limitations of this theoretical treatment have been discussed.     

Effect of layered double hydroxides on the thermal degradation behavior of biodegradable poly(l-lactide) nanocomposites

This study elucidates the thermal degradation behavior of biodegradable poly(l-lactide) (PLLA)/layered double hydroxide (LDH) nanocomposites was explored using thermogravimetric analysis (TGA) and pyrolysis-gas chromatography/mass spectroscopy (Py-GC/MS) in an inert atmosphere. PLLA/LDH nanocomposites were fabricated using PLLA and organically-modified magnesium/aluminum layered double hydroxide (P-LDH) in tetrahydrofuran solution. According to the TGA results, the thermal stability of PLLA/P-LDH nanocomposites was significantly lower than that of pure PLLA matrix, perhaps because P-LDH provides thermal acceleration of the degradation of the underlying polymer from the heat source. The identification of the thermal degradation products by Py-GC/MS evidently shows that introducing P-LDH into PLLA leads to a remarkable change during the thermal degradation process. The main reaction route of neat PLLA was through inter- and intra-transesterification to generate lactides and oligomer. The primary volatile products obtained from PLLA/P-LDH nanocomposites were lactides regardless of the temperature of degradation. These results suggest that the thermal degradation behavior of PLLA/P-LDH nanocomposites is governed by the preferential formation of lactide by the unzipping depolymerization reaction, which is catalyzed by Mg and Al components in P-LDH.     

Thermal and electrical properties of poly(l-lactide)-graft-multiwalled carbon nanotube composites

The dispersion of the nanometer-sized carbon nanotubes in a polymer matrix leads to a marked improvement in the properties of the polymer. This approach can also be applied to biodegradable synthetic aliphatic polyesters such as poly(l-lactide) (PLLA), which has received a great deal of attention due to environmental concerns. In this study, PLLA was melt compounded with multiwalled carbon nanotubes (MWCNTs). A high degree of dispersion of the MWCNTs in the composites was obtained by grafting PLLA onto the MWCNTs (PLLA-g-MWCNTs). After oxidizing the MWCNTs by treating them with strong acids, they were reacted with l-lactide to produce the PLLA-g-MWCNTs. The morphology of the composite was observed with scanning electron microscopy. The mechanical properties of the PLLA/PLLA-g-MWCNT composite were higher than those of the PLLA/MWCNT composite. The thermal stability of the composites was studied using thermogravimetric analysis and their activation energy during thermal degradation was determined using the Kissinger and Flynn-Wall-Ozawa methods. The activation energy of PLLA/PLLA-g-MWCNT was higher than that of PLLA/MWCNT, which indicates that the composite made with the PLLA-g-MWCNTs was more thermally stable than the composite made with the MWCNTs.     

Characterization and release of triptolide-loaded poly (d,l-lactic acid) nanoparticles

Triptolide (TP), which has immunosuppressive effect, anti-neoplastic activity, anti-fertility function and severe toxicities on digestive, urogenital, blood circulatory system, was used as a model drug in this study. TP-loaded poly (d,l-lactic acid) (PLA) nanoparticles were prepared by the modified spontaneous emulsification solvent diffusion method (modified-SESD method). Dynamic light scattering system (DLS), transmission electron microscope (TEM), atomic force microscopy (AFM), differential scanning calorimetry (DSC), X-ray powder diffractometry and Fourier transform infra-red spectroscopy (FT-IR) were employed to characterize the nanoparticles fabricated for size and size distribution, surface morphology, the physical state of drug in nanoparticles, and the interaction between the drug and polymer. Encapsulation efficiency (EE) and the in vitro release of TP in nanoparticles were measured by the reverse phase high-performance liquid chromatography (RP-HPLC). The produced nanoparticles exhibited a narrow size distribution with a mean size of approximately 150 nm and polydispersity index of 0.088. The morphology of the nanoparticles exhibited a fine spherical shape with smooth surfaces without aggregation or adhesion. TP-entrapped in nanoparticles was found in the form of amorphous or semicrystalline. It was found that a weak interaction existed between the drug and polymer. In all experiments, more than 65% of EE were obtained. The in vitro release profile of TP from nanoparticles exhibited a typical biphasic release phenomenon, namely initial burst release and consequently sustained release. In this case, the particle size played an important role for the drug release. The modified-SESD method was a potential and advantage method to produce an ideal polymer nanoparticles for drug delivery system (DDS).     

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.     

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.