Low Molecular Weight Polylactide Research Articles

Pectin-cellulose nanocrystal biocomposites: Tuning of physical properties and biodegradability

The fabrication of pectin-cellulose nanocrystal (CNC) biocomposites has been systematically investigated by blending both polysaccharides at different relative concentrations. Circular free-standing films with a diameter of 9 cm were prepared by simple solution of these carbohydrates in water followed by drop-casting and solvent evaporation. The addition of pectin allows to finely tune the properties of the biocomposites. Textural characterization by AFM showed fibrous morphology and an increase in fiber diameter with pectin content. XRD analysis demonstrated that pectin incorporation also reduced the degree of crystallinity though no specific interaction between both polysaccharides was detected, by ATR-FTIR spectroscopy. The optical properties of these biocomposites were characterized for the first time and it was found that pectin in the blend reduced the reflectance of visible light and increased UV absorbance. Thermal stability, analyzed by TGA, was improved with the incorporation of pectin. Finally, pectin-cellulose nanocrystal biocomposites showed a good biodegradability in seawater, comparable to other common bioplastics such as cellulose and low-molecular weight polylactide, among others.

Effects of molecular weight and crystallizability of polylactide on the cellulose nanocrystal dispersion quality in their nanocomposites

This study investigated how cellulose nanocrystals (CNC) dispersion quality and its percolation network formation could be influenced when using polylactide (PLA) with various molecular weights and crystallizability. In this context, systematic rheological experiments were conducted on PLA/CNC nanocomposites prepared through solution casting method using dimethylformamide (DMF) as the solvent. It was found that lower CNC percolation concentrations could be obtained when a PLA matrix possesses lower molecular weight as the shorter chains and CNCs interpenetration could be facilitated during their dissolution in the solvent. On the other hand, the CNC percolation concentration was further lowered when the PLA with higher crystallizability was used. During the solvent evaporation step that occurred at 85 °C, the isothermal heterogeneous crystallization of PLA around the dispersed CNCs could prevent the driving force of the CNCs towards their re-agglomeration. Therefore, the finest CNC dispersion was appeared in the highly crystallizable low molecular weight PLA through which the rheological properties were dramatically improved and the thermal stability was significantly extended to higher temperatures. The crystallization behavior of the prepared nanocomposites was also analyzed using differential scanning calorimeter and X-ray diffractometer. The thermal degradation behavior of the PLA/CNC nanocomposites were examined through thermogravimetric and rheological analysis.

Highly hydrophilic and stable polylactic acid surface achieved by argon plasma treatment

The effect of modifying additives such as low molecular weight polylactide (PLA) and benzyl alcohol (BA) on the degree of hydrophilicity of high molecular weight PLA before and after plasma treatment with low density and specific power per area was investigated. The lowest water contact angle (WCA) after modification was about 17°. A comparative evaluation of the formed functional groups amount, the hydrophilicity and stability of the plasma modification was carried out. WCA measurements of ageing of modified samples over time up to one year was carried out. It was found that plasma treated PLA films, obtained from tetrahydrofuran solution of high-molecular weight PLA and BA, demonstrated one of the highest ageing stability at high hydrophilicity. At the same time, the increase of the oxygen-containing functional groups amount on the modified PLA surface (about 40%, estimated by XPS) is close to the critical value in point of view of ensuring both high hydrophilicity and stability of the PLA surface after the modification.

Effect of surface modification of nanofibres with glutamic acid peptide on calcium phosphate nucleation and osteogenic differentiation of marrow stromal cells

Biomineralization is mediated by extracellular matrix (ECM) proteins with amino acid sequences rich in glutamic acid. The objective of this study was to investigate the effect of calcium phosphate deposition on aligned nanofibres surface-modified with a glutamic acid peptide on osteogenic differentiation of rat marrow stromal cells. Blend of EEGGC peptide (GLU) conjugated low molecular weight polylactide (PLA) and high molecular weight poly(lactide-co-glycolide) (PLGA) was electrospun to form aligned nanofibres (GLU-NF). The GLU-NF microsheets were incubated in a modified simulated body fluid for nucleation of calcium phosphate crystals on the fibre surface. To achieve a high calcium phosphate to fibre ratio, a layer-by-layer approach was used to improve diffusion of calcium and phosphate ions inside the microsheets. Based on dissipative particle dynamics simulation of PLGA/PLA-GLU fibres, > 80% of GLU peptide was localized to the fibre surface. Calcium phosphate to fibre ratios as high as 200%, between those of cancellous (160%) and cortical (310%) bone, was obtained with the layer-by-layer approach. The extent of osteogenic differentiation and mineralization of marrow stromal cells seeded on GLU-NF microsheets was directly related to the amount of calcium phosphate deposition on the fibres prior to cell seeding. Expression of osteogenic markers osteopontin, alkaline phosphatase (ALP), osteocalcin and type 1 collagen increased gradually with calcium phosphate deposition on GLU-NF microsheets. Results demonstrate that surface modification of aligned synthetic nanofibres with EEGGC peptide dramatically affects nucleation and growth of calcium phosphate crystals on the fibres leading to increased osteogenic differentiation of marrow stromal cells and mineralization.

Drug release kinetics, cell uptake, and tumor toxicity of hybrid VVVVVVKK peptide-assembled polylactide nanoparticles

An exciting approach to tumor delivery is encapsulation of the drug in self-assembled polymer–peptide nanoparticles. The objective of this work was to synthesize a conjugate of low molecular weight polylactide (LMW PLA) and V6K2 peptide and investigate self-assembly, drug release kinetics, cell uptake and toxicity, drug pharmacokinetics, and tumor cell invasion with Doxorubicin (DOX) or paclitaxel (PTX). The results for PLA-V6K2 self-assembled NPs were compared with those of polyethylene glycol stabilized PLA (PLA-EG) NPs. The size of PLA-V6K2 and PLA-EG NPs was 100±20 and 130±50nm, respectively, with polydispersity index of 1.04 and 1.14. The encapsulation efficiency of DOX in PLA-V6K2 and PLA-EG NPs was 44±9% and 55±5%, respectively, and that of PTX was >90 for both NP types. The release of DOX and PTX from PLA-V6K2 was slower than that of PLA-EG, and the release rate was relatively constant with time. Based on molecular dynamic simulation, the less hydrophobic DOX was distributed in the lactide core as well as the peptide shell, while the hydrophobic PTX was localized mainly to the lactide core. PLA-V6K2 NPs had significantly higher cell uptake by 4T1 mouse breast carcinoma cells compared to PLA-EG NPs, which was attributed to the electrostatic interactions between the peptide and negatively charged moieties on the cell membrane. PLA-V6K2 NPs showed no toxicity to marrow stromal cells. DOX-loaded PLA-V6K2 NPs showed higher toxicity to 4T1 cells and the DNA damage response, and apoptosis was delayed compared to the free DOX. DOX or PTX encapsulated in PLA-V6K2 NPs significantly reduced invasion of 4T1 cells compared to those cells treated with the drug in PLA-EG NPs. Invasion of 4T1 cells treated with DOX in PLA-V6K2 and PLA-EG NPs was 5±1% and 30±5%, respectively, and that of PTX was 11±2% and 40±7%. The AUC of DOX in PLA-V6K2 NPs was 67% and 21% higher than those of free DOX and PLA-EG NPs, respectively. DOX-loaded PLA-V6K2 NPs injected in C3HeB/FeJ mice inoculated with MTCL syngeneic breast cancer cells displayed higher tumor toxicity than PLA-EG NPs and lower host toxicity than the free DOX. Cationic PLA-V6K2 NPs with higher tumor toxicity than the PLA-EG NPs are potentially useful in chemotherapy.

Silver N-heterocyclic carbene complexes as initiators for bulk ring-opening polymerization (ROP) of l-lactides

Synthetic, structural and catalysis studies of two silver complexes namely, {[1-(2,4,6-trimethylphenyl)-3-( N-phenylacetamido)imidazol-2-ylidene] 2Ag} +Cl − 1b, supported over an amido-functionalized N-heterocyclic carbene ligand, and [1-( i-propyl)-3-(benzyl)imidazol-2-ylidene]AgCl 2b, supported over a non-functionalized N-heterocyclic carbene ligand, are reported. Specifically, 1b, a cationic complex bearing 2:1 NHC ligand to metal ratio, was obtained from the reaction of 1-(2,4,6-trimethylphenyl)-3-( N-phenylacetamido)imidazolium chloride 1a with Ag 2O in 52% yield. The corresponding 1a was synthesized by the alkylation reaction of 1-(2,4,6-trimethylphenylimidazole) with N-phenyl chloroacetamide in 73% yield. The other silver complex 2b, a neutral complex bearing 1:1 NHC ligand to metal ratio, was obtained from the reaction of 1-( i-propyl)-3-(benzyl)imidazolium chloride 2a with Ag 2O in 42% yield. The 2a was synthesized by the alkylation reaction of 1-( i-propylimidazole) with benzyl chloride in 45% yield. The molecular structures of the imidazolium chloride, 1a, and the silver complexes, 1b and 2b, have been determined by X-ray diffraction studies. The silver complexes, 1b and 2b, successfully catalyze bulk ring-opening polymerization (ROP) of l-lactides at elevated temperatures under solvent-free melt conditions producing moderate to low molecular weight polylactide polymers having narrow molecular weight distributions.

First Example of a Gold(I) N‐Heterocyclic‐Carbene‐Based Initiator for the Bulk Ring‐Opening Polymerization of L‐Lactide

AbstractSynthesis, structure, and catalysis studies of two Au‐ and Ag‐based initiators, namely, [3‐(N‐tert‐butylacetamido)‐1‐(2‐hydroxycyclohexyl)imidazol‐2‐ylidene]AuCl (1c) and [3‐(N‐tert‐butylacetamido)‐1‐(2‐hydroxycyclohexyl)imidazol‐2‐ylidene]AgCl (1b), for the bulk ring‐opening polymerization of L‐lactide are reported. Specifically, gold complex 1c was obtained from silver complex 1b by the transmetalation reaction with (SMe2)AuCl. Silver complex 1b was synthesized by the treatment of 3‐(N‐tert‐butylacetamido)‐1‐(2‐hydroxycyclohexyl)imidazolium chloride (1a) with Ag2O. Compound 1a was synthesized directly from the reaction of N‐tert‐butyl‐2‐chloroacetamide, cyclohexene oxide, and imidazole. The molecular structures of 1a, 1b, and 1c have been determined by X‐ray diffraction studies. The formation of neutral monomeric complexes with linear geometries at the metal centers was observed for both 1b and 1c. The Au and Ag complexes 1c and 1b successfully catalyzed the bulk ring‐opening polymerization of L‐lactide at elevated temperatures under solvent‐free melt conditions to produce moderate to low molecular weight polylactide polymers with narrow molecular weight distributions. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

Radiolabeling, stability, and body distribution in rats, of low molecular weight polylactide homopolymer and polylactide–polyethyleneglycol copolymer

In order to study its fate in vivo, a low molecular-weight polylactide homopolymer was derivatized with a p-methoxyphenyl moiety, so as to make it susceptible to radiolabeling with 125 I . A low molecular weight polylactide–polyethyleneglycol copolymer capped with a p-methoxyphenyl residue was also synthesized. The derivatized polymers were successfully [ 125 I ]iodinated in organic medium. The radiolabeled products were freed from [ 125 I ]iodide by dialysis and shown to be stable for 24 h on incubation at 37°C in buffered saline or in blood. On longer incubation at 37°C in buffered saline the radiolabeled polylactide released [ 125 I ]iodide and [ 125 I ]iodinated 3-( p-methoxyphenyl)propionic acid. The radiolabeled copolymer was more stable on incubation at 37°C in buffered saline, but some [ 125 I ]iodide was released. The tissue distribution of radioactivity was determined 5 min, 1, 5 and 24 h after injecting male rats with 125 I -labeled homopolymer or copolymer. Intravenous, intraperitoneal and subcutaneous injection routes were employed. Further rats were injected with [ 125 I ]iodide, to aid interpretation of the data. After administration of labeled homopolymer, a high concentration of radioactivity was found in the liver tissue. The levels slowly decreased over 24 h, and the polymer was successively found in the small and large intestine and the faeces. This is probably indicative of excretion via the bile. Concurrently radioactivity was excreted in the urine. After administration of labeled copolymer, a high concentration of radioactivity was found in the liver and the residual soft tissue, the latter fraction containing two-thirds of the radioactivity one hour after injection. The precise tissue location that this result indicates was not identified. After 1 h radioactivity was excreted in the faeces, again probably via the bile, and in the urine. Tissue distributions after intraperitoneal or subcutaneous injections were concordant with the above results and interpretations, with the additional factor of slow clearance from the injection site.

Influence of the preparation methods on the drug release behaviour of loperamide-loaded nanoparticles

Polylactide (PLA) or poly(lactide-coglycolide) (PLGA) nanoparticles containing loperamide (LPM) were prepared by an incorporation or adsorption method with the objective of developing nanoparticles with a rapid drug release. The use of polymers such as PLA with lower molecular weights and the addition of sorhitan fatty acid esters (SFAE) for the incorporation led to an almost complete entrapment of LPM in nanoparticles. Preparation of PLA nanoparticles by adsorption was performed by addition of LPM methanol solution before, during and after evaporation of dichloromethane from the system. The adsorption of LPM onto the nanoparticles with low molecular weight PLA (m.w. 2000) showed an isotherm with a good correlation to the Langmuir equation. A high amount of LPM can be entrapped or adsorbed in nanoparticles only with low molecular weights of PLA or PLGA. In the incorporation method, the addition of SFAEs increased drug entrapment. However, in the adsorption method they had no effect on nanoparticle drug adsorption. The drug-release profiles from both nanoparticles, prepared by the adsorption and incorporation methods, were biphasic with an initial rapid release and a second slower release phase, although their initial extents of release were different. The release rates wcrc almost the same for both the adsorption and incorporation method without SFAEs. The addition of SFAEs to the adsorption system increased the extent of drug release from nanoparticles. In conclusion, a rapid loperamide release from nanoparticles can be achicved hy use of PLA or PLGA with low molecular weights and in the adsorption method by the addition of SFAEs.

Cytotoxicity of magnetite-loaded polylactide, polylactide/glycolide particles and solid lipid nanoparticles

Particles from polylactide (PLA), polylactide/glycolide (PLA/GA) and solid lipid nanoparticles (SLN) were produced and loaded with different amounts of magnetite. The in vitro cytotoxicity was determined to assess their toxicological acceptance as intravenous formulation for magnetic resonance imaging and as potential carrier for drug targeting. Viability determinations were performed in suspensions of human granulocytes using the dimethylthiazolyldiphenyltetrazolium (MTT) test. Particle internalization by the granulocytes was followed using luminol enhanced chemiluminescence (CL). The effective concentrations to reduce the viability to 50% (ED 50%) were 0.38% and 0.30% for high and low molecular weight PLA, 0.15% for PLA/GA. The mechanism of toxicity is the intracellular uptake, with the highest toxicity being observed for the faster degrading polymers, low molecular weight PLA and PLA/GA. The solid lipid nanoparticles proved to be the least cytotoxic preparation with an effective concentration (ED 50%) above 10%.

Macromolecular engineering of polylactones and polylactides. XXI. Controlled synthesis of low molecular weight polylactide macromonomers

Macromolecular engineering of polylactones and polylactides. XXI. Controlled synthesis of low molecular weight polylactide macromonomers

Evidence for Ester-Exchange Reactions and Cyclic Oligomer Formation in the Ring-Opening Polymerization of Lactide with Aluminum Complex Initiators

Four polylactide samples, obtained by ring-opening polymerization with an aluminum alkoxide initiator derived from a Schiff's base, were characterized by MALDI-TOF mass spectrometry. The MALDI mass spectra of these polylactides show well-resolved signals that can be reliably assigned to polylactide oligomers. Remarkably, both even-membered and odd-membered oligomers are present in these MALDI spectra. The presence of odd-membered oligomers cannot be explained on the basis of the lactide ring-opening polymerization, and one must admit that ester-exchange reactions do occur parallel to the polymerization process, causing a random cleavage of the polylactide chain. Furthermore, evidence for the presence of cyclic lactides was found in the MALDI-TOF spectrum of a low molecular weight polylactide fraction, indicating that ester exchange occurs also in polylactides by intramolecular end-biting reactions (ring−chain equilibration), with formation of cyclic oligomers.

Preparation and characterization of bupivacaine-loaded polylactide and polylactide-co-glycolide microspheres

Various bupivacaine-loaded microsphere systems have been prepared from polylactide-co-glycolide (PLGA) and from blends of different molecular weight polylactide (PLA) by a solvent evaporation-extraction method. In vitro drug release profiles displayed significant differences between polymers. Among PLA microspheres, the initial release was accelerated with increasing proportion of low molecular weight PLA. Preliminary pharmacokinetic studies following intrathecal and intraperitoneal administration of different bupivacaine-loaded microspheres in rabbits illustrated the controlled release of this drug.