Measurement of Monomer Reactivity Ratios of D,L-3-Methylglycolide with Glycolide or D,L-Lactide

For monomer reactivity ratios study, the copolymerization of D,L-3-methylglycolide (MG) with glycolide (GA) or D,L-lactide (LA) was carried out in bulk to a certain low conversion in the presence of stannous octoate at 140 degrees C. The copolymer compositions were determined by H-1 NMR spectroscopy. The monomer reactivity ratios were evaluated by Fineman-Ross method, Kelen-Tudos method and linear least-squares method. The monomer reactivity ratios of D,L-3-methylglycolide and glycolide or D,L-lactide are r(mg)= 0.73, r(ga)= 1.47; r(mg)= 1.71, r(la)= 0.92, respectively.

A Series of Rare Earth Phenolates Substituted by Alkyl Groups for D,L-Lactide Ring-Opening Polymerization

Single component rare earth phenolates substituted by various alkyl groups have been prepared and the correlation between the aryloxides＇ structure and catalytic activity in the ring-opening polymerization of D,L-lactide has also been investigated.The catalytic activity of all rare earth aryloxides,characteristics of the ring-opening polymerization as well as polymerization kinetics and mechanism were investigated.The results showed that both phenolates＇ catalytic activities and polymerization characteristics changed regularly,keeping in good concordance with variations in substitutents＇ number on phenol and structure of aryloxide ligands.The stronger ability of electron-donation of alkyl groups,the higher catalytic activity.Moreover,the more numbers of substituted alkyl on phenyl ring,the higher catalytic activity.The analyses of polymer ends revealed that the polymerization proceeded via a coordination-acyl-oxygen bond cleavage-insertion mechanism.

THE RING-OPENING POLYMERIZATION OF D,L-LACTIDE WITH ONE COMPONENT RARE EARTH CATALYST

(D, L)-Lactide (LA) was first polymerized with one component of rare earth catalysts [Nd(naph)(3), Nd(oct)(3), Nd(O-iPr)(3), Nd(AcAc)(3), Y(AcAc)(3), Sm(AcAc)(3), Er(AcAc)(3))] respectively in solution and in melt state. The effects of [Cat]/[La] molar ratio, solvents, polymerization time, temperature, various rare earth Elements and ligands were investigated in detail. The results showed that both the conversion of polymerization and the molecular weight (MW) of poly (D, L-Lactide) (PLA) in melt polymerization are higher than that in solution polymerization, but the polymerization rate in melt was lower than in solution. The molecular weight distribution (MWD) of PLA is broader with increasing temperature. X-ray study indicated that PLA obtained by Nd(AcAc)(3) in melt polymerization is an amorphous polymer.

STUDIES ON GRAFT COPOLYMERIZATION OF DL-LACTIDE ON CORN STARCH AND BIODEGRADABILITY OF THE COPOLYMERS

The starch/D,L-lactide graft copolymers were synthesized by reacting D,L-lactide with corn starch in N,N-dimethylacetamide (DMAM) in the presence of triethylamine (NEt3) and anhydrous lithium chloride. The effect of reaction time and the molar ratio of D,L-lactide to glucose structural unit of starch on monomer conversion(C%), graft (G%) and graft efficiency (GE%) were studied. The C%, G% and GE% could approach 37.3%,179.7% and 68.0%, respectively when the molar ratio of D,L-lactide to glucose structural unit of starch is 10:1 and the graft copolymerization was carried out at 80-85℃ for 4 hours under nitrogen atmosphere. The Fourier transforms infra-red (FTIR) spectroscopy, differential scanning calorimetry (DSC) and X-ray diffraction (XRD) spectroscopy were used in order to characterize the graft copolymers. FTIR spectra show that absorption band at 1740 cm-1 confirmed the formation of ester bond, indicating the starch /D,L-lactide graft copolymers were produced, the DSC characteristic results show the melting temperature of the graft copolymer were elevated slightly as the molar ratio of D,L-lactide to glucose structural units of starch increased and the X-ray diffraction spectra show the synthesized graft copolymers were amorphous. The degradability of graft copolymer was tested with the aid of acid, alkali and microbe such as bacillus subtilis and staphylococcus aureus. The results of water resistance show the graft copolymer produced can be used as a component of impermeable coating for cardboard.

The Ring-opening Polymerization of D, L-Lactide Initiated with Stannous Octoate

The ring-opening polymerization of D, L-lactide in the melt was systematically investigated by using stannous octoate as the initiator. The molecular weight of poly (D, L-lactide) was characterized with M,. Mn and Mw respectively. The results indicated that five variables, namely purity of monomer, initiator to monomer ratio, vacuum level, polymerization temperature and polymerization time had different influences on the molecular weight and molecular weight distribution of poly(D. L-lactide).

Co-delivery of resveratrol and docetaxel via polymeric micelles to improve the treatment of drug-resistant tumors

Co-delivery of anti-cancer drugs is promising to improve the efficacy of cancer treatment.This study was aiming to investigate the potential of concurrent delivery of resveratrol(RES)and docetaxel(DTX)via polymeric nanocarriers to treat breast cancer.To this end,methoxyl poly(ethylene glycol)-poly(D,L-lactide)copolymer(mPEG-PDLA)was prepared and characterized using FTIR and 1H NMR,and their molecular weights were determined by GPC.Isobologram analysis and combination index calculation were performed to find the optimal ratio between RES and DTX to against human breast adenocarcinoma cell line(MCF-7 cells).Subsequently,RES and DTX were loaded in the mPEG-PDLA micelles simultaneously,and the morphology,particle size distribution,in vitro release,pharmacokinetic profiles,as well as cytotoxicity to the MCF-7 cells were characterized.IC50 of RES and DTX in MCF-7 cells were determined to be 23.0μg/ml and 10.4μg/ml,respectively,while a lower IC50 of 4.8μg/ml of the combination of RES and DTX was obtained.The combination of RES and DTX at a ratio of 1:1(w/w)generated stronger synergistic effect than other ratios in the MCF-7 cells.RES and DTX loaded mPEG-PDLA micelles exhibited prolonged release profiles,and enhanced cytotoxicity in vitro against MCF-7 cells.The AUC(0→t)of DTX and RES in mPEG-PDLA micelles after i.v.administration to rats were 3.0-fold and 1.6-fold higher than that of i.v.injections of the individual drugs.These findings indicated that the co-delivery of RES and DTX using mPEG-PDLA micelles could have better treatment of tumors.

Biodegradable Blend Nanoparticles of Amphiphilic Diblock Copolymers Prepared by Nano-Precipitation Method

Nanoparticles of biodegradable methoxy poly(ethylene glycol)-b-polyester amphiphilic diblock copolymers have widely investigated for use as controlled release drug delivery carriers. In this work, blend nanoparticles of methoxy poly(ethylene glycol)-b-poly(D,L-lactide) (MPEG-b-PDLL) and methoxy poly(ethylene glycol)-b-poly(ε-caprolactone) (MPEG- b-PCL) were prepared by nano-precipitation method without any surfactants. 1H-NMR spectra showed significant difference in integral peak areas, suggesting the nanoparticles with different MPEG-b-PDLL/MPEG-b-PCL blend ratios can be prepared. Transmission electron microscope revealed the blend nanoparticles had nearly spherical in shape with smooth surface. Average size of the blend nanoparticles obtained from light-scattering analysis slightly decreased with increase in blend ratio of MPEG-b-PCL. The MPEG-b-PDLL and MPEG-b-PCL were amorphous and semi-crystalline, respectively. Thermal transition properties of the blend nanoparticles were studied with differential scanning calorimetry (DSC). The DSC results showed that glass transition temperatures of the blend nanoparticles decreased and heats of melting steadily increased, while the melting temperature did not change as the MPEG-b-PCL blend ratio increased. This indicates the miscibility of MPEG-b-PDLL and MPEG-b-PCL in the amorphous phase of the blend nanoparticles. Thermogravimetric analysis showed that the blend nanoparticles clearly exhibited two thermal decomposition steps due to MPEG-b-PDLL decomposition followed with MPEG-b-PCL. The blend nanoparticles had two temperatures of maximum decomposition rate (Td, max) accorded to each blend component. The Td, max of MPEG-b- PDLL phase significantly decreased, while Td, max of MPEG-b-PCL phase did not change as the MPEG-b-PCL blend ratio increased. These results suggested that the desired thermal properties of blend nanoparticles can be tailored by varying the blend ratio.

Prevention of Staphylococcus aureus biofilm formation on metallic surgical implants via controlled release of gentamicin

Implant associated infections are a critical health concern following orthopaedic surgery. Sustained local delivery of antibiotics has been suggested as a means of preventing these infections. Poly(D,L-lactide) (PDLLA) is a biodegradable polymer that has been used to coat implants for the delivery of antibiotics and other bioactive molecules. While effective, these studies show that antibiotics are released in a burst profile. Here we evaluated a method for controlled release of gentamicin from implant surfaces using the palmitate alkyl salt to decrease its solubility in aqueous solution. Steel Kirschner wires (K-wires) were coated with Gentamicin-palmitate (GP)-PDLLA, gentamicin sulphate (GS)-PDLLA or vancomycin sulphate (VS)-PDLLA, and elution of antibiotics from coated K-wires investigated using HPLC/MS/ MS. In contrast to burst antibiotic release from the GS-PDLLA and VS-PDLLA groups, GP was released in a slower sustained manner. Colonisation and initial attachment of Staphylococcus aureus Xen29 to gentamicin-coated K-wires was reduced by 90% when compared to the non-coated control group. However there was no statistical difference in recovery of bacteria from GS or GP groups. Bacteria recovered from VS-PDLLA coated K-wires decreased by 36%. Bioluminescence emitted by S. aureus Xen29 was also reduced over seven days in the antibiotic control groups, demonstrating that growth and biofilm development over the longer term was impaired by antibiotic-PDLLA coating. These results indicate that using alkyl salts of antibiotics may be an effective strategy for controlling the release of antibiotics from implants.

ANTIBACTERIAL POLY(D,L-LACTIDE)(PDLLA)FIBROUS MEMBRANES MODIFIED WITH QUATERNARY AMMONIUM MOIETIES

Antibacterial poly（D,L-lactide） （PDLLA） fibrous membranes were developed via electrospinning, followed by surface modification which involved plasma pretreatment, UV-induced graft copolymerization of 4-vinylpyridine （4VP） and quaternization of the grafted pyridine groups with hexylbromide. The success of modification with quaternized pyridinium groups on the PDLLA fibrous membranes was ascertained by X-ray photoelectron spectroscopy （XPS）. The antibacterial activities of these membranes were assessed against Gram-positive Staphylococcus aureus （S. aureus） and Gram-negative Escherichia coli （E. coli）. The PDLLA fibrous membranes modified with quatemized pyridinium groups showed antibacterial efficiency against both bacteria as high as 99.999%. The results demonstrated that the antibacterial activity was based on the interaction of the positive charge of pyridinium group and negatively charged cell membrane of bacteria, resulting in loss of membrane permeability and cell leakage.

Preparation and Characterization of Polymeric Micelles from Poly (D, L-lactide) and Methoxypolyethylene Glycol Block Copolymers as Potential Drug Carriers

Amphiphilic diblock copolymers composed of methoxy polyethylene glycol （MePEG） and poly（D,L-lactide） （PDLLA） were prepared for the preparation of polymeric micelles, The use of MePEG-PDLLA as drug carriers has been reported in the open literature, but there are only few data on the application of a series of MePEG-PDLLA copolymers with different lengths in the medical field, The shape of the polymeric micelles is also important in drug delivery, Studies on in vitro drug release profiles require a good sink condition. The critical micelle concentration of a series of MePEG-PDLLA has a significant role in drug release. To estimate their feasibility as a drug carrier, polymeric micelles made of MePEG-PDLLA block copolymer were prepared by the oil in water （O/VV） emulsion method. From dynamic light scattering （DLS） measurements, the size of the micelle formed was less than 200 nm, The critical micelle concentration of polymeric micelles with various compositions was determined using pyrene as a fluorescence probe. The critical micelle concentration decreased with increasing number of hydrophobic segments. MePEG-PDLLA micelles have a considerably low critical micelle concentration （0.4～0.5 μg/mL）, which is apparently an advantage in utilizing these micelles as drug carriers. The morphology of the polymeric micelles was observed using scanning electron microscopy （SEM） and transmission electron microscopy （TEM）, The micelles were found to be nearly spherical. The yield of the polymeric micelles obtained from the O/W method is as high as 85%.

Surface Treatment and Biomimetic Mineralization of Porous Microspheres Fabricated by Calcium Gluconate-g-Poly(D,L-lactide)

Porous hybrid microspheres were fabricated by the synthesized calcium gluconate-g-poly（D,L-lactide） （CG-g- PDLLA） composites. These hybrid microspheres were treated with an alkaline solution for different period of time to control the amount of generated carboxylate groups and remained CG on the surface. The microspheres were then incubated in a supersaturated simulated body fluid （1.5 SBF） solution for different time to investigate their biomimetic mineralization behavior. The depositions were found to have a fine cluster morphology, a similar crystal structure and chemical structure to natural hydroxyapatite, and a medium Ca/P of approximately 1.30. The effect of surface treating time on the structure and mineralization behavior of these microspheres has been discussed in detail. The results indicate that the nucleation and growth of apatite on the surface are influenced by the induced carboxylate groups and the remained CG. The hybrid CG-g- PDLLA microspheres have the potential as a novel alternative in bone tissue engineering.

Tissue engineering and peripheral nerve regeneration (Ⅲ)——Sciatic nerve regeneration with PDLLA nerve guide

The biodegradation rate and biocompatibility of poly(d, / -lactide) (PDLLA) in vivo were evaluated. The aim of this study was to establish a nerve guide constructed by the PDLLA with 3-D microenvironment and to repair a 10 mm of sciatic nerve gap in rats. The process of the nerve regeneration was investigated by histological assessment, electrophysiological examination, and determination of wet weight recovery rate of the gastrocnemius muscle. After 3 weeks, the nerve guide had changed from a transparent to an opaque status. The conduit was degraded and absorbed partly and had lost their strength with breakage at the 9th week of postoperation. At the conclusion of 12 weeks, proximal and distal end of nerves were anastomosed by nerve regeneration and the conduit vanished completely. The results suggest that PDLLA conduits may serve for peripheral nerve regeneration and PDLLA is a sort of hopeful candidate for tissue engineering.

Process conditions for preparing well-defined nano- and microparticles as delivery systems of alkyl gallates

Dextran-covered poly(D,L-lactide) (PLA) nano-and microparticles were prepared using an emulsion/solvent evaporation (or diffusion) process for the encapsulation of alkyl gallates (AGs).In the first step,a solution of PLA and AG in ethyl acetate was emulsified to give an aqueous phase containing a hydrophobically modified dextran,which acted as a stabilizer.The second step involved solvent evaporation or diffusion.The emulsification conditions were varied,which allowed for the preparation of nanoand microparticle suspensions covering a wide range of surface-average particle diameters from 0.1 μm (sonication) to 500 μm (stirring with a magnetic bar),with narrow and reproducible size distributions.Continuous microfluidic emulsification in a flow-focusing system led to well-defined microparticles,in the 10-50 μm range.Particles loaded with octyl gallate (OG) and nonyl gallate (NG) were obtained using the three processes,and we showed that the encapsulation efficiency of OG and NG varied significantly depending on the emulsification process.The effect of particle size on the mechanism of in vitro release of encapsulated AGs was investigated.The kinetics of release were controlled either by Fickian diffusion within the solid core or swelling and hydrolytic degradation of the PLA matrix,depending on the pH of the external medium.

Synthesis, Structure of Zinc Complexes Containing Sulfon- ylated Binaphtholate Ligands and Their Catalytic Activities towards Ring-Opening Polymerization of Lactide and ε-Caprolactone

Reaction of sulfonylated binaphthol [2-hydroxy-2＇-tosyloxy-l,l-binaphthyl （la, Ts-Binol） or 2-hydroxy-2＇- （phenylsulfonyloxy）-l,l-binaphthyl （lb, Ps-Binol）] with 1 equiv, of ZnEt2 afforded zinc complexes [（Ys-Binol）ZnEt]2 （2a） and [（Ps-Binol）ZnEt]2 （2b）. Further reaction of zinc complexes 2a and 2b with benzyl alco- hol （BnOH） gave the zinc benzyloxide [（Ts-Binol）2Zn2（OBn）2]2 （3a） and [（Ps-Binol）2Znz（OBn）2]2 （3b）. Alterna- tively, the zinc benzyloxides 3a and 3b could also be obtained by reaction of compound la or lb with Zn（OBn）2 （in situ reaction of ZnEt2 and BnOH）. The complexes were fully characterized by elemental analyses and spectroscopic analyses, and complexes 2a, 2b and 3a were further characterized by single-crystal X-ray analyses. The catalytic activities of these zinc complexes towards ring-opening polymerization of ε-caprolactone and D,L-lactide were studied.