Lactide Units Research Articles

Tethered drug release from model contact lenses

AbstractDrug delivery to the eye remains a challenge due to low compliance and high amounts of drug loss resulting from anatomical barriers. Contact lens‐based delivery systems offer many advantages since their increased corneal residence time can increase drug bioavailability. A releasable, sustained delivery system from a contact lens has been evaluated in the current work. Using a labile lactide spacer, comprised of poly(ethylene glycol) methacrylate, varying numbers of lactide units and succinic anhydride, a model drug, R‐roscovitine, was covalently incorporated into model silicone lenses (consisting of 80 mol% N,N‐dimethylacrylamide and 20 mol% of a modified silicone). This enabled a greater amount of the drug to remain in the material following extraction with isopropyl alcohol, a common purification procedure used in lens manufacturing. The incorporation of the tether and drug did not substantially alter the bulk properties of the materials, with their water content remaining between 32% and 36% and their transmittance remaining at over 90% at 600 nm. Drug release from these materials exceeded 2 weeks, with the longer lactide tethers showing greater release as expected. This demonstrates that these covalently modified materials have the potential to be used to deliver drugs in a sustained manner. © 2022 Society of Industrial Chemistry.

Synthesis of lactide from alkyl lactates catalyzed by lanthanide salts

Cerium salt exhibited a highest catalytic activity in the conversion of ethyl and isopropyl oligolactates into lactide. A maximum yield of the target product was reached at the concentration of CeCl3·7H2O ranging from 1 to 4 mol% relative to the lactide units in ethyl and isopropyl oligolactates. A gradual reduction of the pressure from 50 to 5 Torr along with the temperature increase from 180 to 230 °C during depolymerization resulted in the product containing up to 94% lactide.

Poly(2-isopropyl-2-oxazoline)-b-poly(lactide) (PiPOx-b-PLA) Nanoparticles in Water: Interblock van der Waals Attraction Opposes Amphiphilic Phase Separation.

Poly(2-isopropyl-2-oxazoline)-b-poly(lactide) (PiPOx-b-PLA) diblock copolymers comprise two miscible blocks: the hydrophilic and thermosensitive PiPOx and the hydrophobic PLA, a biocompatible and biodegradable polyester. They self-assemble in water, forming stable dispersions of nanoparticles with hydrodynamic radii (Rh) ranging from ∼18 to 60 nm, depending on their molar mass, the relative size of the two blocks, and the configuration of the lactide unit. Evidence from 1H nuclear magnetic resonance spectroscopy, light scattering, small-angle neutron scattering, and cryo-transmission electron microscopy indicates that the nanoparticles do not adopt the typical core–shell morphology. Aqueous nanoparticle dispersions heated from 20 to 80 °C were monitored by turbidimetry and microcalorimetry. Nanoparticles of copolymers containing a poly(dl-lactide) block coagulated irreversibly upon heating to 50 °C, forming particles of various shapes (Rh ∼ 200–500 nm). Dispersions of PiPOx-b-poly(l-lactide) coagulated to a lesser extent or remained stable upon heating. From the entire experimental evidence, we conclude that PiPOx-b-PLA nanoparticles consist of a core of PLA/PiPOx chains associated via dipole–dipole interactions of the PLA and PiPOx carbonyl groups. The core is surrounded by tethered PiPOx loops and tails responsible for the colloidal stability of the nanoparticles in water. While the core of all nanoparticles studied contains associated PiPOx and PLA blocks, fine details of the nanoparticles morphology vary predictably with the size and composition of the copolymers, yielding particles of distinctive thermosensitivity in aqueous dispersions.

Clean production of new functional coatings of magnetic nanoparticles from sustainable resources

Magnetic nanoparticles coated with functional polymers play an important role in clean ways of catalysis and water treatment as well as in nanomedicine. Known systems either contain only terminal functions or polymers with pendant positively charged groups. Poly(tartaric acid) (PTA) as a new polymer with multiple pendant negatively charged carboxylate groups was pursued useful for coating magnetic nanoparticles. Simple heating of tartaric acid as a sustainable natural product without using a solvent or a catalyst under controlled conditions leads to poly(tartaric acid). The reaction runs in the solid state by elimination of water and traces of carbon oxides. The structure of the resulting poly(tartaric acid) consists mainly of polyester moieties with pendant carboxyl groups and some lactide units. It was elucidated by mass spectrometry, solid-state 13C nuclear magnetic resonance (13C ss-NMR) and Fourier-transform infrared spectroscopy (FTIR). The properties of the products depend in part on the type of starting materials (L-tartaric acid or D,L-tartaric acid). Pendant carboxyl and hydroxyl groups provide hydrophilicity and the possibility to link functions of interest. The PTA was used as new functional coatings for magnetite nanoparticles in a clean way by mixing the components and magnetic separation. The chemical stability of the magnetic nanoparticles covered by PTA was studied by UV-VIS spectroscopy in water for three weeks. Further linkage of amino-containing entities of practical interest was demonstrated by covalently binding of glucosamine.

Incorporation of chloramphenicol and captopril into poly(GL)‐b‐poly(GL‐co‐TMC‐co‐CL)‐b‐poly(GL) monofilar surgical sutures

ABSTRACTIncorporation of chloramphenicol and captopril into coated and uncoated monofilament sutures was evaluated, as well as the derived bactericide and wound healing effects. To this end, a commercially available suture and an amorphous random copolymer constituted by trimethylene carbonate and lactide units were considered. The suture had a segmented architecture based on polyglycolide hard blocks and a soft block constituted by glycolide, trimethylene carbonate and ε‐caprolactone units. Chloramphenicol was better loaded when the coating copolymer was employed due to its protective effect whereas captopril showed an opposite behavior due to partial solubilization during immersion in the coating bath. Interestingly, the release behavior was very different for the two studied drugs since a significant retention of chloramphenicol was always detected, suggesting the establishment of interactions between drug and copolymers. On the other hand, delivery of captopril showed a typical dose dependent behavior. A low in vitro toxicity of the two drugs was determined considering both epithelial‐like and fibroblast‐like cells. Bactericide effect of chloramphenicol against Gram‐negative and Gram‐positive bacteria was demonstrated at a dose that was non‐toxic for all assayed cells. An accelerating wound healing effect of captopril was also demonstrated for early events. In this case, the use of a coating copolymer was fundamental to avoid cytotoxic effects on highly loaded sutures. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 44762.

聚（ε-己内酯-L-丙交酯）无规共聚物与聚乳酸共混材料的制备与性能

通过开环聚合,合成不同比例的e-己内酯（e-CL）与L-丙交酯（L-LA）的无规共聚物P（CL/LLA）。将上述共聚物P（CL/LLA）与聚乳酸（PLLA）共混,制备了PLA/P（CL/LLA）共混材料。并对其相容性、热性能、力学性能进行了研究。结果表明,共聚物P（CL/LLA）与PLA相容性与共聚物中LA单元含量和链段的平均长度有密切关系,P（CL/LLA）中LA链段平均长度达到3.4以上时,可以与PLA很好的相互作用。同时共聚物P（CL/LLA）中—CL—链段有很好的柔性,可以很好的改善PLLA的韧性,使PLLA材料的断裂伸长率达到500%以上。

Sequential Structure, Crystallization, and Properties of Biodegradable Poly(ethylene Terephthalate-Co-Ethylene Oxide-Co-Lactide) Copolyester

The sequential structure, isothermal crystallization, tensile property, and degradation behavior of poly(ethylene terephthalate-co-ethylene oxide-co-lactide) (ETOLA) copolyester based on melt transesterification of poly(ethylene terephthalate) with poly(ethylene oxide) and oligo(lactic acid) was investigated. The degree of randomness was calculated to be 0.38, showing the incorporation of poly(ethylene oxide) (PEO) blocks into the homogeneous sequences of ethylene terephthalate (ET) and lactide (LA) units. The isothermal crystallization kinetics results revealed that the crystallization activation energy of the copolyester calculated using the Arrhenius’ equation was lower than that reported for poly(ethylene terephthalate) (PET), indicating that the addition of PEO and LA units into PET retarded the crystallization of PET. The copolyester exhibited the same crystal structure at different crystallization temperatures, similar to that of PET homopolymer, based on wide angle X-ray diffraction results. The size of the spherulites of ETOLA increased with crystallization temperature. The increase of crystallization temperature reduced the elongation at break of the copolyesters, as well as the enzymatic degradation.

Synthesis and characterization of statistical copolymers of trimethylene carbonate and l-lactide using Mg(II)/Ti(IV) mixed alkoxides as initiator system

Copolymers of trimethylene carbonate and l-lactide with distinct compositions were prepared in bulk employing a novel initiator comprising two biocompatible metals. The NMR analyses showed that the initiator, Catylen® S200, has preference for l-lactide incorporation during the copolymerization, which is attested by the deviations in copolymer compositions compared to the monomers feed ratios and differences between the calculated and the observed average block lengths of lactide units. Nevertheless, the presence of higher contents of trimethylene carbonate led to a higher degree of transesterification, furnishing a copolymer with composition close to a true statistical copolymer when the content of carbonate trimethylene is 51wt%. The effects of the composition in the thermal properties and the crystallinity of the copolymers were also investigated by DSC and WAXD respectively.

Effects of repeat unit sequence distribution and residual catalyst on thermal degradation of poly(l-lactide/ε-caprolactone) statistical copolymers

To evaluate the effects of residual catalyst and chain microstructural features on the thermal decomposition of poly(l-lactide/ε-caprolactone) (PLCL), poly(l-lactide) (PLLA) and poly(ε-caprolactone) (PCL) homopolymers and their copolymers were synthesized by ring opening polymerization (ROP) using stannous octoate (SnOct2) or bismuth (III) subsalicylate (BiSS) as catalyst. Thermogravimetric analysis (TGA) confirmed that ε-caprolactone repeat units are more thermally resistant than lactide units, both by comparison of the two homopolymers behavior and also by a detailed thermogravimetric analysis of PLCL copolymers of well resolved chain microstructures. It was noticed a large influence of metal-catalyzed depolymerization in all polymers, yet more significant for tin. In this regard the homopolymers having a higher residual metal content displayed onsets of thermal degradation at lower temperature values, e.g. 233 °C and 287 °C for PLLA and PCL containing ∼4500 ppm of Sn vs. 271 °C and 345 °C for PLLA and PCL containing ∼50 ppm. The type and content of the catalysts were revealed responsible of the final distribution of sequences obtained during the PLCL copolymers synthesis. 1H NMR spectroscopy revealed a higher randomness character (R→1) and shorter lactide average sequence lengths (lLA) for PLCL copolymers when they were BiSS-initiated; these copolymers degraded homogeneously almost entirely in a single stage and presented higher resistance to thermal degradation. In contrast, the more blocky PLCLs, containing >250 ppm of residual Sn, were found more sensitive to thermal degradation and degraded heterogeneously presenting two different peaks in the Differential TG curve. The 1H NMR analysis of a blocky PLCL sample (66% of LA, R∼0.5 and ∼500 ppm of Sn) further demonstrated that LA-rich sequences degrade at lower temperatures and, at a later stage, those of CL. It was also proved that the mechanism of this first stage of weight loss, occurring at lower temperatures, is highly influenced by the lLA, since increased rates of weight loss and heavier weight losses were associated to higher lLA values.

광학이성질체를 이용한 폴리락타이드 혼합물의 가수분해성 조절

생분해성 폴리락타이드의 분해속도를 조절하기 위하여 <TEX>$d$</TEX>-lactide와 <TEX>$l$</TEX>-lactide의 함량을 달리하여 다양한 stereochemical PLAs를 개환중합으로 합성하고 Langmuir 단분자막 장치를 이용하여 알칼리 분해속도를 측정하였다. 알칼리 수용액상에서 혼합 단분자막의 분해속도를 각 혼합고분자의 광학적 순도(100, 99, 97, 95%)의 항으로 측정하였다. 스테레오 콤플렉스에 기인하는 혼합물의 용융온도는 혼합물 성분의 광학적 순도가 증가함에 따라 증가하였다. 분해거동은 100% 광학적 순도를 가진 혼합물은 각 단일중합체보다 느린 분해속도를 나타내는 반면 다른 혼합물들은 2단계의 분해거동을 나타내었는데 1단계에서는 콤플렉스를 형성하지 않은 부분에서의 분해로 단일중합체에 비해 빠른 분해속도를 나타내었고 2단계에서는 100% 광학적 순도를 가진 혼합물과 유사하게 느린 분해속도를 나타내었다. 이러한 결과는 폴리락타이드의 stereochemistry와 스테레오 콤플렉스를 이용하여 알칼리 분해속도를 조절할 수 있음을 의미한다. To control degradation rate of biodegradable poly(lactide)s (PLA), the stereochemical PLAs with different ratios of <TEX>$d$</TEX>-lactide and <TEX>$l$</TEX>-lactide units were synthesized by the ring open polymerization and a degradation behavior was measured by a Langmuir film balance. Degradation rates of mixture monolayers on alkaline subphase were investigated as a function of optical purity of mixture component, 100, 99, 97 and 95%. As increasing their optical purity, melting temperatures of mixtures from stereocomplexation increased. The degradation rate of mixture monolayer with 100% optical purity was much slower than that of each homopolymer one and the others showed 2 step degradation behaviors. In the first step, the degradation which is faster than that of each homopolymer occurs in the uncomplexed region, and secondly, the degradation occurred in the complexed region which showed similar degradation rate to that of 100% optical purity. These results indicate that the alkaline degradation of stereochemical PLAs could be controlled by stereochemistry and stereocomplexation between enantiomer PLAs.

Determination of the Molar-Mass Averages of Random Poly(aspartate-co-lactide) Copolymers by Tuning the Ionic Strength of the Solvent

Water-soluble sodium poly(aspartate-co-lactide) (PALNa) copolymers with a molar ratio of aspartate-to-lactide units equal to 1:0.6, 1:1.0 and 1:1.5 were studied using NMR spectroscopy to determine the composition as well as SEC-MALS and static light-scattering measurements to determine the molar-mass characteristics of the copolymers. In the copolymer aqueous solutions, high-molar-mass species were detected, most probably due to the incomplete dissolution of the samples. The molar-mass averages determined in water with added simple electrolyte, i.e., NaCl, were much lower than the values determined in pure water. The concentration of the salt, which allows dissolution on a molecular level, and the separation predominantly according to a size-exclusion mechanism depend on the chemical composition of the PALNa copolymers. The optimal mobile phase for the PALNa-1/0.6 and the PALNa-1/1.0 copolymers was 0.1 M NaCl at pH 9, and for the PALNa-1/1.5 copolymer with a higher content of lactide units it was 0.05 M NaCl at pH 9. The molar-mass averages of the PALNa-1/1.0 copolymer, determined by SEC-MALS and static light-scattering measurements, were comparable.

Characterization of the mechanical properties, crystallization, and enzymatic degradation behavior of poly(butylene succinate‐co‐ethyleneoxide‐co‐DL‐lactide) copolyesters

AbstractA series of aliphatic biodegradable poly (butylene succinate‐co‐ethyleneoxide‐co‐DL‐lactide) copolyesters were synthesized by the polycondensation in the presence of dimethyl succinate, 1,4‐butanediol, poly(ethylene glycol), and DL‐oligo(lactic acid) (OLA). The composition, as well as the sequential structure of the copolyesters, was carefully investigated by 1H‐NMR. The crystallization behaviors, crystal structure, and spherulite morphology of the copolyesters were analyzed by differential scanning calorimetry, wide angle X‐ray diffraction, and polarizing optical microscopy, respectively. The results indicate that the sequence length of butylene succinate (BS) decreased as the OLA feed molar ratio increasing. The crystallization behavior of the copolyesters was influenced by the composition and sequence length of BS, which further tuned the mechanical properties of the copolyesters. The copolyesters formed the crystal structures and spherulites similar to those of PBS. The incorporation of more content of ethylene oxide (EO) units into the copolyesters led to the enhanced hydrophilicity. The more content of lactide units in the copolyesters facilitated the degradation in the presence of enzymes. The morphology of the copolyester films after degradation was also studied by the scanning electron microscopy. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012

Biodegradable poly(α‐hydroxy ester) blended microspheres as suitable carriers for retinal pigment epithelium cell transplantation

Five blends of poly(L-lactic acid) (PLLA) with poly(D,L-lactic-co-glycolic acid) (PLGA) were used to prepare microcarriers by a solvent evaporation technique. Microcarriers were evaluated as suitable scaffolds to facilitate retinal pigment epithelium (RPE) cell transplantation. The blend ratios were 90:10, 75:25, 50:50, 25:75, 10:90 (PLLA:PLGA). Samples of each microcarrier blend were coated with an extracellular matrix protein. Coated and uncoated microcarriers were seeded with a human RPE cell line. As the lactide unit content increased the size of microcarriers generally became larger and the surface more irregular. Cells remained proliferative and retained phenotype as confirmed by immunocytochemistry. Blends rich in PLLA were superior for maintenance of RPE cell viability. This study demonstrates for the first time the feasibility of using microcarriers as a vehicle for retinal cell transplantation for ocular disease.

Thermo-responsive hydrogels based on highly branched poly(ethylene glycol)–poly( l-lactide) copolymers

Highly branched poly(ethylene glycol)–poly( l-lactide) (PEG–PLLA) copolymers were synthesized by a coupling reaction of eight-arm amine-functionalized PEG and macromonomers having 2 PLLA arms and a N-hydroxysuccinimide activated ester group at the branching point. A coupling efficiency of approximately 50% was achieved. Copolymer solutions in water (⩾4 wt.%) showed a phase transition from gel to sol upon increasing the temperature. The critical gelation concentration at 20 °C decreased with increasing PLLA block length. The gel–sol transition of a 12 wt.% aqueous copolymer solution increased from 4 °C for a copolymer with PLLA blocks with 3 repeating lactide units per arm to 38 °C for a copolymer with PLLA blocks with 5 repeating lactide units per arm. Furthermore, the gel–sol transition temperature increased with increasing copolymer concentration, and could be tuned closely to body temperature, which makes these hydrogels interesting as injectable systems for in situ gel formation.

Effect of Encapsulating a Pseudo-Decapeptide Containing Arginine on PLGA: A Solid-State NMR Study

The effects of incorporating an amorphous decapeptide in PLGA on the cooperative and local motions of the polymer chains have been evaluated. Whereas assessment of the bulk properties is used traditionally for studies of host-guest interactions, there are only rare examples where molecular-level understanding of such amorphous host-guest systems has been sought. Moreover, addressing the mechanism of interactions and stabilisation of a drug in a polymeric network is a key factor for the achievement of reproducibility of the formulations and ultimately the preparation of composites able to deliver drugs with consistency. We present a methodology combining the study of the dynamics by solid-state NMR and the characterisation of the bulk properties to address and localise the presence of interactions in PLGA/guest composites. The results (estimation of relaxation times, 2D wideline separation and T(g) measurements) suggested (1) the existence of a drug-polymer solid solution and (2) significant changes in the local dynamics of both the drug and the polymer in their composites depending on the loading level. The changes in the local dynamics as well as in the cooperative motions of the polymer chains in the composites were attributed to the formation of guest-polymer interactions. Differentiation of the affinity of glycolide or lactide units for interactions was also apparent.

Synthesis of poly(propylene-co-lactide carbonate) and hydrolysis of the terpolymer

A new aliphatic polycarbonate, terpolymer of carbon dioxide, propylene oxide, and dl-lactide, was synthesized by using a polymer-supported bimetallic complex as a catalyst. The terpolymer prepared was characterized by FT-IR, 1H NMR, 13C NMR, 1H–1H COSY, DSC, and WAXD measurements. The influence of molar ratio on the terpolymerization progress was investigated. The results showed that lactide unit was inserted into the backbone of CO2–PO successfully. Because of the existence of the lactide ester unit, the terpolymers had stronger degradability than poly(propylene carbonate).

Novel poly(butylene succinate-co-lactic acid) copolyesters: Synthesis, crystallization, and enzymatic degradation

A series of aliphatic biodegradable poly(butylene succinate-co- dl-lactide) (PBSLA) copolyesters were synthesized with the aim of improving the degradation rate of poly(butylene succinate) (PBS) by incorporation of dl-oligo(lactic acid) (OLA) into the PBS molecular chains. The composition and sequential structure of the aliphatic copolyesters were investigated by proton nuclear magnetic resonance ( 1H NMR) spectroscopy. The crystallization behaviors, the crystal structure and morphology of the copolyesters were investigated by using differential scanning calorimetry (DSC), wide angle X-ray diffraction (WAXD) and polarizing optical microscopy (POM), respectively. The results indicate that the crystallization of the copolyesters was restricted by the incorporation of lactide (LA) units, which further tuned the mechanical properties of the copolyesters. The copolyesters could form complete spherulites and exhibit the same crystal structure as that of PBS. Enzymatic study indicated that the copolyesters with higher content of LA units degraded faster, and the degradation began in the amorphous regions and then in the crystalline regions. The morphology and the resulting degradation products of the copolyesters were investigated by scanning electron microscopy (SEM) and 1H NMR analysis during the degradation process.

Optimisation of polymer scaffolds for retinal pigment epithelium (RPE) cell transplantation

AimTo evaluate a variety of copolymers as suitable scaffolds to facilitate retinal pigment epithelium (RPE) transplantation.MethodsFive blends of poly(l-lactic acid) (PLLA) with poly(d,l-lactic-glycolic acid) (PLGA) were manufactured by a solid–liquid...

Inimer-Promoted Synthesis of Branched and Hyperbranched Polylactide Copolymers

A series of (hyper)branched poly(l-lactide)(PLLA) copolymers has been prepared by ring-opening multibranching copolymerization of l-lactide with a hydroxyl-functional (ABB′) lactone inimer, 5HDON (5-hydroxymethyl-1,4-dioxane-2-on). Polymerization was conducted in bulk and solution and catalyzed either by stanneous-2-ethyl hexanoate (Sn(Oct)2) or an organic base, 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD). Precise structural characterization of the resulting branched copolyester structures was accomplished by a combination of 2D NMR techniques, relying on the comparison with model compounds. The 5HDON inimer was employed in 1% to 20% fractions and is incorporated either as a dendritic unit or as a focal structure, but hardly in the linear mode. A detailed reaction mechanism was derived from kinetic investigation of the polymerization via NMR spectroscopy, preparative and analytical SEC and MALDI-TOF MS. The evolution and the extent of branching have been monitored and quantified. Both the degree of branching (DB = 2D(HDON)/2D(HDON) + L(lactide); DB = 0.02−0.22) and the molecular weight (MN = 1200−34000 g/mol) could be tailored by variation of the monomer/inimer ratio. For Sn(Oct)2 catalyzed polymerization approximately 50% of the inimer is transformed into dendritic units. In the case of TBD catalysis, the formation of dendritic units was suppressed at room temperature, resulting in linear poly(lactide) functionalized with a lactone end group. The fozcal 5HDON unit of the branched structures is susceptible to further functionalization, for example, by reaction with primary hydroxyl groups, leading to branched polylactide functionalized with precisely one single dye label at the focal moiety. The formation of previously absent linear repeat units from the addition of terminal lactide units to focal 5HDON units was observed when heating the polymers above Tg for prolonged times. This reaction was accompanied by a further increase in the molecular weight of the branched copolyesters.

Synthesis and structure of biodegradable hexylene terephthalate-co-lactide copolyesters

To obtain a biodegradable polymer material with satisfactory thermal properties, higher elongation and modulus of elasticity, a new copolyester, poly(hexylene terephthalate-co-lactide) (PHTL), was synthesized via direct polycondensation from terephthaloyl dichloride, 1,6-hexanediol and oligo(lactic acid). The resulting copolyesters were characterized by proton nuclear magnetic resonance (1H NMR), differential scanning calorimetry (DSC), thermogravimetry (TG) and wide-angle X-ray scattering (WAXS). By using the relative integral areas of the dyad peaks in 1H NMR spectrum of copolyesters PHTL, the sequence lengths of the hexylene terephthalate and lactide units in the resultant copolyesters are 3.5 and 1.5, respectively. Compared to poly(hexylene terephthalate) (PHT), PHTL has lower Tm but higher Tg due to the incorporation of lactide unit into the main chains of copolyesters. The degradation test of copolyesters under a physiological condition shows that the degradability of PHTL is sped up due to incorporation of lactide segments.