(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 sta...(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.展开更多
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 na...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.展开更多
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-vinylpyridi...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.展开更多
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 b...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%.展开更多
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 o...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.展开更多
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...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.展开更多
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 ...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.展开更多
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...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.展开更多
基金This work was supported by the National Natural Science Foundation of China and the Laboratory of Rare-earth Chemistry and Physics,Changchun Institute of Applied Chemistry,Academia Sinica
文摘(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.
基金the Liaoning Province Pan Deng Xue Zhe Grant(M.Yang)Liaoning Provincial Education officer’s Excellent Talents Supporting Plan(D.Cun)National Natural Science Foundation of China(No.81302720 and 81573380)for financial support。
文摘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.
基金supported by the National Natural Science Foundation of China(Nos.50573011 and 50673019)Southeast University Foundation(Nos.9207040015 and 4022001023)
文摘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.
基金Supported by the National Natural Science Foundation of China (No. 29836130)
文摘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%.
基金supported by the National Natural Science Foundation of China(Nos.51025314 and 21104089)the Fundamental Research Funds for the Central Universities(No.ZY1632)
文摘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.
文摘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.
文摘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.
基金Acknowledgements This work was supported by the High Technology Research and Development Program (Grant No. 863-715-002-0210) and the National Basic Science Research and Development Grants (Grant No. 973, G1999054306).
文摘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.