The aim of the present study was to develop a novel long-acting Poly(lactic-co-glycolic acid)(PLGA)-based microspheres formulation of Bisdemethoxycurcum(BDMC) by emulsionsolvent evaporation method. Meanwhile, the effe...The aim of the present study was to develop a novel long-acting Poly(lactic-co-glycolic acid)(PLGA)-based microspheres formulation of Bisdemethoxycurcum(BDMC) by emulsionsolvent evaporation method. Meanwhile, the effects of the volume ratio of the dispersed phase and continuous phase, the concentration of PLGA and PVA, the theoretical drug loading and stirring speed were investigated. The mean diameter of the microspheres was 8.5 μm and the size distribution was narrow. The encapsulation efficiency(EE) and drug loading efficiency(DLE) of BDME loaded PLGA microspheres(BDMC-PLGA-MS) was 94.18% and 8.14%,respectively. In an in vitro study of drug release, it can be concluded that the BDMC-PLGAMS exhibited sustained and long-term release properties for 96 h. Stability studies suggested that the microspheres we prepared had a very good stability. Furthermore, the results of an in vivo study indicated that the BDMC-PLGA-MS had sustained release effect and was mainly distributed in the lung tissue, and less distribution in other tissues, which indicated that microspheres could be an effective parenteral carrier for the delivery of BDMC in lung cancer treatment.展开更多
Drug-loaded microspheres are significant for the development of modern pharmaceutical products. It is well known that the taken of aspirin for long-term increases the risk of serious gastrointestinal complications, th...Drug-loaded microspheres are significant for the development of modern pharmaceutical products. It is well known that the taken of aspirin for long-term increases the risk of serious gastrointestinal complications, therefore a controllable delivery of aspirin is of importance to lighten those side effects. In this work, poly(lactic acid)(PLA) was chosen as the carrier to prepare PLA-aspirin microspheres by using the traditional and the improved solvent evaporation methods. It was found that no matter which experimental condition was, the encapsulation efficiency of aspirin was higher by using the improved method than that of the traditional method. Specifically, when the concentration of polyvinyl alcohol = 1%(mass),the polymer concentration = 1:20, the oil/water rate = 1:2.5, PLA-aspirin microspheres were obtained via the improved method with a high yield of 82.83%(mass) and an encapsulation efficiency of 44.09%. PLAaspirin microspheres were then prepared continuously using the improved method, which further enhanced the encapsulation efficiency to 54.56%. Approximate 85% aspirin released from microspheres within 7 days. Obvious degradation which was represented by reduction on hardness was observed by soaking microspheres in PBS for 60 days. This work is of interest because it provides a continuous route to prepare PLA-aspirin microspheres continuously with a high drug encapsulation efficiency.展开更多
Monodisperse poly(poly(ethyleneglycol) methyl ether acrylate-co-acrylic acid) (poly(PEGMA-co-AA)) microspheres were prepared by distillation-precipitation polymerization with divinylbenzene (DVB) as crosslin...Monodisperse poly(poly(ethyleneglycol) methyl ether acrylate-co-acrylic acid) (poly(PEGMA-co-AA)) microspheres were prepared by distillation-precipitation polymerization with divinylbenzene (DVB) as crosslinker with 2,2'- azobisisobutyronitrile (AIBN) as initiator in neat acetonitrile without stirring. Under various reaction conditions, four distinct morphologies including the sol, microemulsion, microgels and microspheres were formed during the distillation of the solvent from the reaction system. A 2D morphological map was established as a function of crosslinker concentration and the polar monomer AA concentration, in comonomer feed in the transition between the morphology domains. The effect of the covalent crosslinker DVB on the morphology of the polymer network was investigated in detail at AA fraction of 40 vol%. The ratios of acid to ethylene oxide units presenting in the comonomers dramatically affected the polymer-polymer interaction and hence the morphology of the resultant polymer network. The covalent crosslinking by DVB and the hydrogen bonding crosslinking between two acid units as well as between the acid and ethylene oxide unit played key roles in the formation of monodisperse polymer microspheres.展开更多
Micron-sized polymer particles from single poly(4-butyltriphenylamine) (PBTPA) homopolymer, binary polymer blend [PBTPA/poly(methyl methacrylate) (PMMA)], and ternary polymer blend (PBTPA/PBTPA-b-PMMA/PMMA) via a solv...Micron-sized polymer particles from single poly(4-butyltriphenylamine) (PBTPA) homopolymer, binary polymer blend [PBTPA/poly(methyl methacrylate) (PMMA)], and ternary polymer blend (PBTPA/PBTPA-b-PMMA/PMMA) via a solvent evaporation method, and the surface morphologies and inside structure of resulting particles were investigated. Spherical homopolymer particles with smooth surface were resulted from PBTPA with low molecular weight. In the case of binary blends (PBTPA/PMMA = 1/1), Janus (low molecular weight) and dumbbell (high molecular weight) type morphologies were observed. The particles based on ternary blends containing PBTPA-b-PMMA showed core-shell type morphologies (PMMA;core, PBTPA;shell). Degree of engulfment of PMMArich domain increased with the content of the block copolymer. The decrease of domain size was not observed although the block copolymer had a suitable structure as a compatibilizer for the blend. It was also found that the initial concentration of polymer solution had an effect on the final morphology.展开更多
Poly-dl-lactide-poly(ethylene glycol) (PELA) triblock copolymers were synthesized with lanthanum acetate as the initiator. PELA microspheres with entrapped Vibrio Cholera antigen and outer membrane protein (OMP) were ...Poly-dl-lactide-poly(ethylene glycol) (PELA) triblock copolymers were synthesized with lanthanum acetate as the initiator. PELA microspheres with entrapped Vibrio Cholera antigen and outer membrane protein (OMP) were prepared by a double emulsion W/O/W based on solvent extraction methods. The obtained microspheres showed smooth and spherical surface and their size varied between 0.5 and 5.0 mu m, which are suitable for oral targeting delivery system. The distribution tests in rabbits and mice through scanning electronic micrography and fluorescence microscope indicated that microspheres have successfully reached the immunization-related tissues, such as the liver, spleen and intestinal peyer's patches, following oral administration. The PELA microspheres were also evaluated as an efficient antigen delivery system by enhancing a higher protective ratio against live Vibrios Cholera.展开更多
Titania-grafted poly(styrene-divinylbenzene)(TiO2/PSt-DVB) nanocomposite microspheres were prepared by an open-ring reaction and radical grafting copolymerization method. The TiO2 nanoparticles were first modified...Titania-grafted poly(styrene-divinylbenzene)(TiO2/PSt-DVB) nanocomposite microspheres were prepared by an open-ring reaction and radical grafting copolymerization method. The TiO2 nanoparticles were first modified by attachment of epoxy groups to their surfaces to provide reactive groups that could covalently bond to the polymer (PSt-DVB) microspheres. The nanocomposite obtained was characterized by FTIR, SEM, XRD, and TGA analyses as well as UV-Vis spectrophotometry. The results indicated that the TiO2 nanoparticles were uniformly grafted onto the surface of the polymer microsphere producing grain sizes of about 5―10 μm. The modified TiO2 showed better UV absorbing property than the unmodified form, and the nanocomposite also retained the same UV absorbing property as the free modified TiO2 nanoparticle.展开更多
BACKGROUND: Nogo A antigen is the major inhibiting factor blocking regeneration of the injured spinal cord. Neutralizing Nogo A antigens using Nogo A antibodies may help promote neurite regeneration and nervous funct...BACKGROUND: Nogo A antigen is the major inhibiting factor blocking regeneration of the injured spinal cord. Neutralizing Nogo A antigens using Nogo A antibodies may help promote neurite regeneration and nervous function recovery. For successful regeneration, sustained release of the antibody from a biodegradable material loaded with Nogo A antibodies to the injury site is required. OBJECTIVE: To compare the therapeutic effects of poly lactic-co-glycolic acid (PLGA)-Nogo A antibody delayed-release microspheres and Nogo A antibody alone on spinal regeneration in Sprague-Dawley rats with complete transverse injury to the spinal cord. DESIGN, TIME AND SETTING: A randomized, controlled animal trial was performed at the Pharmacological Laboratory of West China Center of Medical Sciences, Sichuan University, between October 2007 and January 2008. MATERIALS: Goat anti-rat Nogo A monoclonal antibody was purchased from Santa, American; goat anti-rat neurofilament 200 monoclonal antibody was from Zhongshan Goldenbridge, Beijing, China; PLGA-Nogo A antibody delayed-release microspheres were provided by the College of Pharmacy, Sichuan University. METHODS: A total of 36 adult female Sprague Dawley rats were used to establish models of completely transected spinal cord injury, at T10. Animals were randomly divided into three groups (n=12): model, Nogo A antibody alone, and Nogo A antibody delayed-release microsphere groups. After transverse injury of the spinal cord, 50 μ L normal saline solution, 50 μL normal saline solution containing 50μL g Nogo A antibody, and 50 μL normal saline solution containing 50 μg Nogo A antibody microspheres were administered to the respective groups at the injury site. MAIN OUTCOME MEASURES: The expression of Nogo A and neurofilament 200 in injured spinal cord was tested immunohistochemically, and motor function of rats was assessed by Basso-Beattie-Bresnahan (BBB) locomotor rating scale. RESULTS: Four weeks after injury, expression of Nogo A in microsphere group was significantly less than model and Nogo A antibody alone groups (P 〈 0.05); while there was no significant difference between model and Nogo A antibody alone groups (P 〉 0.05). Ten weeks after injury, microsphere group showed a significantly greater expression of neurofilament 200 than model and Nogo A antibody alone groups (P 〈 0.05); while no significant difference was found between model and Nogo A antibody alone groups (P 〉 0.05). At postoperative weeks 5 and 6, the score of BBB locomotor rating scale in microsphere group was significantly greater than the model group (P 〈 0.05), and at postoperative weeks 7 10, the score was much greater than model and Nogo A antibody alone groups (P 〈 0.05). CONCLUSION: Nogo A antibody delayed-release microspheres decreased Nogo A expression, increased neurofilament 200 expression in the injured spinal cord of rats, and promoted recovery of motor function through sustained drug release over a long-term period.展开更多
Poly ( l- lactide- co-glycolide ) ( PLGA ) with different compositions was prepared using stannous octaoate as catalyst by bulk ring-opening copolymerization of l-lactide and glycolide. The structure and properti...Poly ( l- lactide- co-glycolide ) ( PLGA ) with different compositions was prepared using stannous octaoate as catalyst by bulk ring-opening copolymerization of l-lactide and glycolide. The structure and properties of the PLGA copolymers were cbaracterized by means of attenuated total reflectance-Fourier transform infrared (ATR-FTIR), ^1H NMR, differential scanning calorimeter ( DSC and X-ray diffraction (XRD) methods, The experimented results indicate that the synthetic conditions and the composition of copolymers have art obvious influence on the structure of PLGA copolymers, The degradation rate of eopolymers increased with the increasing of the glycolide component in the copolymers.展开更多
Electrospun aligned ultrafine fibers of poly( lactide-coglycolide)( PLGA) can be used to construct biomimetic scaffolds for engineering those structurally anisotropic and dense tissues( e. g.,tendon,ligament,etc.). Bu...Electrospun aligned ultrafine fibers of poly( lactide-coglycolide)( PLGA) can be used to construct biomimetic scaffolds for engineering those structurally anisotropic and dense tissues( e. g.,tendon,ligament,etc.). But the acidic degradation products of the PLGA could result in p H decrease in the vicinity of the scaffolds,which may give rise to biocompatibility concerns. To address the noted problem, this study was designed to evaluate the p Hcompensation capacity of using Lysine( Lys) —a kind of basic amino acid on the acidic degradation products of PLGA. Ultrafine PLGA( 50∶ 50) fibers with 0,10%,20%,and 30% by weight of Lys loadings were prepared by a stable jet electrospinning( SJES)approach. The morphology,structure,and mechanical properties of the electrospun aligned fibrous mats of Lys-incorporated PLGA( 50∶50) were characterized by scanning electron microscope( SEM),Fourier transform infrared spectroscopy( FTIR),and tensile testing,respectively. Thereafter,the fibrous PLGA( 50 ∶50) scaffolds were subjected to degradation by being immersed in phosphate buffered saline( PBS,p H 6. 86) solution at 37 ℃ for 5weeks. Our results show that the formed Lys / PLGA composite ultrafine fibers have a well-aligned and uniform morphology with a fineness of ca. 1 #m in diameter. Introduction of Lys led to increased mechanical performance; that is,when the Lys loading is less than 30%,tensile strength and Young's modulus of the aligned Lys / PLGA fibers reached up to the impressive values of 84. 5 MPa and 2. 4 GPa,respectively. Degradation results show that the p H of the PLGA group fell to 5. 6 in 5 weeks while the p H of the Lys /PLGA groups with 10%,20%, and 30% of Lys loadings was maintained at 6. 3, 6. 5 and 6. 7, respectively. This work demonstrated that incorporation of Lys into electrospun PLGA fibers could be an effective approach in mediating the p H decrease caused by the acidic degradation products of the PLGA.展开更多
The purposes of this research were to synthesize and characterize star-shaped poly lactide-co-glycolide-β-cyclo-dextrin (PLGA-β-CD) copolymer by reacting L-lactide, glycolide and β-cyclodextrin in the presence of s...The purposes of this research were to synthesize and characterize star-shaped poly lactide-co-glycolide-β-cyclo-dextrin (PLGA-β-CD) copolymer by reacting L-lactide, glycolide and β-cyclodextrin in the presence of stannous octoate as a catalyst. The structure of PLGA-β-CD copolymer was confirmed with 1H-NMR, 13C-NMR and FT-IR spectra. Albumin as a model peptide drug was encapsulated within nanoparticles made of PLGA-β-CD with a modified double emulsion method. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) photomicrographs showed that the nanoparticles have the mean diameter within the range of 80 - 210 nm. Also they were almost spherical in shape. Effects of the experimental parameters, such as copolymer composition, copolymer concentration, and reaction temperature, on particular size and encapsulation efficiency were investigated.展开更多
PolyDL-lactide (PDLLA) and the block copolymer, polyDL-lactide-b-poly(ethylene glycol)-b-polyDL-lactide (PELA) were used as the microsphere matrix to encapsulate plasmid DNA. The PDLLA, PELA, pBR322-loaded PDLLA and p...PolyDL-lactide (PDLLA) and the block copolymer, polyDL-lactide-b-poly(ethylene glycol)-b-polyDL-lactide (PELA) were used as the microsphere matrix to encapsulate plasmid DNA. The PDLLA, PELA, pBR322-loaded PDLLA and pBR322-loaded PELA microspheres were prepared by solvent extraction method based on the formation of multiple w1/o/w2 emulsion. The microspheres were characterized by surface morphology, mean particle size, particle size distribution and loading efficiency. The integrity of DNA molecules after being extracted from microspheres was determined by agarose gel electrophoresis. The result suggested that plasmid DNA molecules could retain their integrity after being encapsulated by PELA. The PELA microspheres could prevent plasmid DNA from being digested by DNase. The in vitro degradation and release profiles of plasmid DNA-loaded microspheres were measured in pH = 7.4 buffer solution at 37 °C. The in vitro degradation profiles of the microspheres were evaluated by the deterioration in microspheres surface morphology, the molecular weight reduction of polymer, the mass loss of microspheres, the changes of pH values of degradation medium, and the changes of particle size. The in vitro release profiles of the microspheres were assessed by measurement of the amount of DNA presented in the release medium at determined intervals. The release profiles were correlation with the degradation profiles. The release of plasmid DNA from PELA microspheres showed a similar biphasic trend, that is, an initial burst release was followed by a slow, but sustained release.展开更多
Objective To investigate the effect of the implant composite of poly lactide-co-glycolide(PLGA)and bone mesenchymal stem cells (BMSCs) modified by basic fibroblast growth factor (bFGF) on injured spinal cord in rats.M...Objective To investigate the effect of the implant composite of poly lactide-co-glycolide(PLGA)and bone mesenchymal stem cells (BMSCs) modified by basic fibroblast growth factor (bFGF) on injured spinal cord in rats.Methods Two hundred and展开更多
Biodegradable polymer poly(lactic-co-glycolic acid)(PLGA) was used to encapsulate the pharmacological activity metabolite of tolterodine by means of O/W emulsion solvent evaporation method via homogenization in th...Biodegradable polymer poly(lactic-co-glycolic acid)(PLGA) was used to encapsulate the pharmacological activity metabolite of tolterodine by means of O/W emulsion solvent evaporation method via homogenization in the emulsification process. The influences of preparation parameters were investigated. The results indicate that increa- sing PLGA concentration from 15% to 40% made the encapsulation efficiency of 5-hydroxymethyl derivative of tol- terodine(5-HMT) increased from 55.39% to 76.32%, and the particle size increased from 34.33 μm to 70,78 lain. In addition, when homogenization speed increased from 850 r/min to 2300 r/min, both particle size and encapsulation efficiency of microspheres decreased. An increase in the volume of aqueous phase led to higher encapsulation efficiency and bigger particle size. Increasing temperature made encapsulation efficiency and particle size change significantly. While reaction temperature increased from 20 ℃ to 50 ℃, the encapsulation efficiency decreased from 70.44% to 24.07%, and particle size increased from 38.66 μm to 69.38 μm. High reaction temperature(over 40 ℃) may lead to porous surface of microspheres. Porous surface, encapsulation efficiency and particle size influenced on the in vitro release of 5-HMT together.展开更多
The purpose of this study was to evaluate the effect of poly(lactide-co-glycolic acid) delayed-release microspheres,which were prepared using glial cell line-derived neurotrophic factor(GDNF),on the delayed-releas...The purpose of this study was to evaluate the effect of poly(lactide-co-glycolic acid) delayed-release microspheres,which were prepared using glial cell line-derived neurotrophic factor(GDNF),on the delayed-release,controllability,and protection of GDNF activity.The present study is the first to combine chondroitinase ABC,GDNF,and Nogo A antibody delayed-release microspheres for the treatment of spinal cord injury.Results show that the combined therapy of chondroitinase ABC,GDNF,and Nogo A antibody microspheres can increase the immunoreaction of neurofilament 200 in the injured spinal cord,and this therapeutic effect was better than chondroitinase ABC,GDNF,or Nogo A antibody microspheres administered singularly.展开更多
When a protein is encapsulated into poly( DL -lactide-co-glycolide)(PLGA) microspheres by means of the double-emulsion method,the harsh microspheres formation process including ultrasonification,exposure to an organic...When a protein is encapsulated into poly( DL -lactide-co-glycolide)(PLGA) microspheres by means of the double-emulsion method,the harsh microspheres formation process including ultrasonification,exposure to an organic solvent and a polymer may cause the denaturation of the protein. In this study,we investigated the enzymatic activity change and the effect of the excipients on the stability of recombinant human Cu,Zn-superoxide dismutase(rhCu,Zn-SOD) during the emulsification. The specific activity recovery was found to be concentration dependent and the excipients involved such as PEG 600 and Tween 20,and trehalose were shown to increase the stability of rhCu,Zn-SOD. The protein structural integrity within the microspheres was analyzed by FTIR. The structure of rhCu,Zn-SOD within PLGA microspheres containing trehalose was found to be similar to that of the native solid state,whereas the protein encapsulated during the preparation in the absence of any excipient changed due to the possible hydrophobic interaction with the polymer. The results suggest that a rational stability strategy for protein to be encapsulated into microspheres should aim at different processes.展开更多
The combination of micro-carriers and polymer scaffolds as promising bone grafts have attracted considerable interest in recent decades.The poly(L-lactic acid)/poly(lactic-co-glycolic acid)/polycaprolactone(PLLA/PLGA/...The combination of micro-carriers and polymer scaffolds as promising bone grafts have attracted considerable interest in recent decades.The poly(L-lactic acid)/poly(lactic-co-glycolic acid)/polycaprolactone(PLLA/PLGA/PCL)composite scaffold with porous structure was fabricated by thermally induced phase separation(TIPS).Dexamethasone(DEX)was incorporated into PLGA microspheres and then loaded on the PLLA/PLGA/PCL scaffoldtopreparethedesiredcompositescaffold.The physicochemical properties of the prepared composite scaffold were characterized.The morphology of rat bone marrow mesenchymal stem cells(BMSCs)grown on scaffolds was observed using scanning electron microscope(SEM)and fluorescence microscope.The resultsshowedthatthePLLA/PLGA/PCLscaffoldhad interconnected macropores and biomimetic nanofibrous structure.In addition,DEX can be released from scaffold in a sustained manner.More importantly,DEX loaded composite scaffold can effectively support the proliferation of BMSCs as indicated by fluorescence observation and cell proliferation assay.The results suggested that the prepared PLLA/PLGA/PCL composite scaffold incorporating drug-loaded PLGA microspheres could hold great potential for bone tissue engineering applications.展开更多
文摘The aim of the present study was to develop a novel long-acting Poly(lactic-co-glycolic acid)(PLGA)-based microspheres formulation of Bisdemethoxycurcum(BDMC) by emulsionsolvent evaporation method. Meanwhile, the effects of the volume ratio of the dispersed phase and continuous phase, the concentration of PLGA and PVA, the theoretical drug loading and stirring speed were investigated. The mean diameter of the microspheres was 8.5 μm and the size distribution was narrow. The encapsulation efficiency(EE) and drug loading efficiency(DLE) of BDME loaded PLGA microspheres(BDMC-PLGA-MS) was 94.18% and 8.14%,respectively. In an in vitro study of drug release, it can be concluded that the BDMC-PLGAMS exhibited sustained and long-term release properties for 96 h. Stability studies suggested that the microspheres we prepared had a very good stability. Furthermore, the results of an in vivo study indicated that the BDMC-PLGA-MS had sustained release effect and was mainly distributed in the lung tissue, and less distribution in other tissues, which indicated that microspheres could be an effective parenteral carrier for the delivery of BDMC in lung cancer treatment.
基金financially supported by National Natural Science Foundation of China (22068018)Yunnan Ten Thousand Talents Plan Young & Elite Talents Project。
文摘Drug-loaded microspheres are significant for the development of modern pharmaceutical products. It is well known that the taken of aspirin for long-term increases the risk of serious gastrointestinal complications, therefore a controllable delivery of aspirin is of importance to lighten those side effects. In this work, poly(lactic acid)(PLA) was chosen as the carrier to prepare PLA-aspirin microspheres by using the traditional and the improved solvent evaporation methods. It was found that no matter which experimental condition was, the encapsulation efficiency of aspirin was higher by using the improved method than that of the traditional method. Specifically, when the concentration of polyvinyl alcohol = 1%(mass),the polymer concentration = 1:20, the oil/water rate = 1:2.5, PLA-aspirin microspheres were obtained via the improved method with a high yield of 82.83%(mass) and an encapsulation efficiency of 44.09%. PLAaspirin microspheres were then prepared continuously using the improved method, which further enhanced the encapsulation efficiency to 54.56%. Approximate 85% aspirin released from microspheres within 7 days. Obvious degradation which was represented by reduction on hardness was observed by soaking microspheres in PBS for 60 days. This work is of interest because it provides a continuous route to prepare PLA-aspirin microspheres continuously with a high drug encapsulation efficiency.
基金This work was supported in part by the National Science Foundation of China (No. 20504015)the starting project for young teachers from the Ministry of Education, China.
文摘Monodisperse poly(poly(ethyleneglycol) methyl ether acrylate-co-acrylic acid) (poly(PEGMA-co-AA)) microspheres were prepared by distillation-precipitation polymerization with divinylbenzene (DVB) as crosslinker with 2,2'- azobisisobutyronitrile (AIBN) as initiator in neat acetonitrile without stirring. Under various reaction conditions, four distinct morphologies including the sol, microemulsion, microgels and microspheres were formed during the distillation of the solvent from the reaction system. A 2D morphological map was established as a function of crosslinker concentration and the polar monomer AA concentration, in comonomer feed in the transition between the morphology domains. The effect of the covalent crosslinker DVB on the morphology of the polymer network was investigated in detail at AA fraction of 40 vol%. The ratios of acid to ethylene oxide units presenting in the comonomers dramatically affected the polymer-polymer interaction and hence the morphology of the resultant polymer network. The covalent crosslinking by DVB and the hydrogen bonding crosslinking between two acid units as well as between the acid and ethylene oxide unit played key roles in the formation of monodisperse polymer microspheres.
文摘Micron-sized polymer particles from single poly(4-butyltriphenylamine) (PBTPA) homopolymer, binary polymer blend [PBTPA/poly(methyl methacrylate) (PMMA)], and ternary polymer blend (PBTPA/PBTPA-b-PMMA/PMMA) via a solvent evaporation method, and the surface morphologies and inside structure of resulting particles were investigated. Spherical homopolymer particles with smooth surface were resulted from PBTPA with low molecular weight. In the case of binary blends (PBTPA/PMMA = 1/1), Janus (low molecular weight) and dumbbell (high molecular weight) type morphologies were observed. The particles based on ternary blends containing PBTPA-b-PMMA showed core-shell type morphologies (PMMA;core, PBTPA;shell). Degree of engulfment of PMMArich domain increased with the content of the block copolymer. The decrease of domain size was not observed although the block copolymer had a suitable structure as a compatibilizer for the blend. It was also found that the initial concentration of polymer solution had an effect on the final morphology.
基金The project was supported by the National Natural Science Foundation of China(No.29774034).
文摘Poly-dl-lactide-poly(ethylene glycol) (PELA) triblock copolymers were synthesized with lanthanum acetate as the initiator. PELA microspheres with entrapped Vibrio Cholera antigen and outer membrane protein (OMP) were prepared by a double emulsion W/O/W based on solvent extraction methods. The obtained microspheres showed smooth and spherical surface and their size varied between 0.5 and 5.0 mu m, which are suitable for oral targeting delivery system. The distribution tests in rabbits and mice through scanning electronic micrography and fluorescence microscope indicated that microspheres have successfully reached the immunization-related tissues, such as the liver, spleen and intestinal peyer's patches, following oral administration. The PELA microspheres were also evaluated as an efficient antigen delivery system by enhancing a higher protective ratio against live Vibrios Cholera.
基金Fosan Scientific Special Funds of Production-Study-Research(No.2006A034)
文摘Titania-grafted poly(styrene-divinylbenzene)(TiO2/PSt-DVB) nanocomposite microspheres were prepared by an open-ring reaction and radical grafting copolymerization method. The TiO2 nanoparticles were first modified by attachment of epoxy groups to their surfaces to provide reactive groups that could covalently bond to the polymer (PSt-DVB) microspheres. The nanocomposite obtained was characterized by FTIR, SEM, XRD, and TGA analyses as well as UV-Vis spectrophotometry. The results indicated that the TiO2 nanoparticles were uniformly grafted onto the surface of the polymer microsphere producing grain sizes of about 5―10 μm. The modified TiO2 showed better UV absorbing property than the unmodified form, and the nanocomposite also retained the same UV absorbing property as the free modified TiO2 nanoparticle.
基金the National Natural Science Foundation of China,No.30471759
文摘BACKGROUND: Nogo A antigen is the major inhibiting factor blocking regeneration of the injured spinal cord. Neutralizing Nogo A antigens using Nogo A antibodies may help promote neurite regeneration and nervous function recovery. For successful regeneration, sustained release of the antibody from a biodegradable material loaded with Nogo A antibodies to the injury site is required. OBJECTIVE: To compare the therapeutic effects of poly lactic-co-glycolic acid (PLGA)-Nogo A antibody delayed-release microspheres and Nogo A antibody alone on spinal regeneration in Sprague-Dawley rats with complete transverse injury to the spinal cord. DESIGN, TIME AND SETTING: A randomized, controlled animal trial was performed at the Pharmacological Laboratory of West China Center of Medical Sciences, Sichuan University, between October 2007 and January 2008. MATERIALS: Goat anti-rat Nogo A monoclonal antibody was purchased from Santa, American; goat anti-rat neurofilament 200 monoclonal antibody was from Zhongshan Goldenbridge, Beijing, China; PLGA-Nogo A antibody delayed-release microspheres were provided by the College of Pharmacy, Sichuan University. METHODS: A total of 36 adult female Sprague Dawley rats were used to establish models of completely transected spinal cord injury, at T10. Animals were randomly divided into three groups (n=12): model, Nogo A antibody alone, and Nogo A antibody delayed-release microsphere groups. After transverse injury of the spinal cord, 50 μ L normal saline solution, 50 μL normal saline solution containing 50μL g Nogo A antibody, and 50 μL normal saline solution containing 50 μg Nogo A antibody microspheres were administered to the respective groups at the injury site. MAIN OUTCOME MEASURES: The expression of Nogo A and neurofilament 200 in injured spinal cord was tested immunohistochemically, and motor function of rats was assessed by Basso-Beattie-Bresnahan (BBB) locomotor rating scale. RESULTS: Four weeks after injury, expression of Nogo A in microsphere group was significantly less than model and Nogo A antibody alone groups (P 〈 0.05); while there was no significant difference between model and Nogo A antibody alone groups (P 〉 0.05). Ten weeks after injury, microsphere group showed a significantly greater expression of neurofilament 200 than model and Nogo A antibody alone groups (P 〈 0.05); while no significant difference was found between model and Nogo A antibody alone groups (P 〉 0.05). At postoperative weeks 5 and 6, the score of BBB locomotor rating scale in microsphere group was significantly greater than the model group (P 〈 0.05), and at postoperative weeks 7 10, the score was much greater than model and Nogo A antibody alone groups (P 〈 0.05). CONCLUSION: Nogo A antibody delayed-release microspheres decreased Nogo A expression, increased neurofilament 200 expression in the injured spinal cord of rats, and promoted recovery of motor function through sustained drug release over a long-term period.
文摘Poly ( l- lactide- co-glycolide ) ( PLGA ) with different compositions was prepared using stannous octaoate as catalyst by bulk ring-opening copolymerization of l-lactide and glycolide. The structure and properties of the PLGA copolymers were cbaracterized by means of attenuated total reflectance-Fourier transform infrared (ATR-FTIR), ^1H NMR, differential scanning calorimeter ( DSC and X-ray diffraction (XRD) methods, The experimented results indicate that the synthetic conditions and the composition of copolymers have art obvious influence on the structure of PLGA copolymers, The degradation rate of eopolymers increased with the increasing of the glycolide component in the copolymers.
基金Fundamental Research Funds for the Central Universities,China(No.14D110519)Pujiang Talent Program Funded by theScience and Technology Commission of Shanghai M unicipality,China(No.10PJ1400200)National Natural Science Foundation of China(No.51073032)
文摘Electrospun aligned ultrafine fibers of poly( lactide-coglycolide)( PLGA) can be used to construct biomimetic scaffolds for engineering those structurally anisotropic and dense tissues( e. g.,tendon,ligament,etc.). But the acidic degradation products of the PLGA could result in p H decrease in the vicinity of the scaffolds,which may give rise to biocompatibility concerns. To address the noted problem, this study was designed to evaluate the p Hcompensation capacity of using Lysine( Lys) —a kind of basic amino acid on the acidic degradation products of PLGA. Ultrafine PLGA( 50∶ 50) fibers with 0,10%,20%,and 30% by weight of Lys loadings were prepared by a stable jet electrospinning( SJES)approach. The morphology,structure,and mechanical properties of the electrospun aligned fibrous mats of Lys-incorporated PLGA( 50∶50) were characterized by scanning electron microscope( SEM),Fourier transform infrared spectroscopy( FTIR),and tensile testing,respectively. Thereafter,the fibrous PLGA( 50 ∶50) scaffolds were subjected to degradation by being immersed in phosphate buffered saline( PBS,p H 6. 86) solution at 37 ℃ for 5weeks. Our results show that the formed Lys / PLGA composite ultrafine fibers have a well-aligned and uniform morphology with a fineness of ca. 1 #m in diameter. Introduction of Lys led to increased mechanical performance; that is,when the Lys loading is less than 30%,tensile strength and Young's modulus of the aligned Lys / PLGA fibers reached up to the impressive values of 84. 5 MPa and 2. 4 GPa,respectively. Degradation results show that the p H of the PLGA group fell to 5. 6 in 5 weeks while the p H of the Lys /PLGA groups with 10%,20%, and 30% of Lys loadings was maintained at 6. 3, 6. 5 and 6. 7, respectively. This work demonstrated that incorporation of Lys into electrospun PLGA fibers could be an effective approach in mediating the p H decrease caused by the acidic degradation products of the PLGA.
文摘The purposes of this research were to synthesize and characterize star-shaped poly lactide-co-glycolide-β-cyclo-dextrin (PLGA-β-CD) copolymer by reacting L-lactide, glycolide and β-cyclodextrin in the presence of stannous octoate as a catalyst. The structure of PLGA-β-CD copolymer was confirmed with 1H-NMR, 13C-NMR and FT-IR spectra. Albumin as a model peptide drug was encapsulated within nanoparticles made of PLGA-β-CD with a modified double emulsion method. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) photomicrographs showed that the nanoparticles have the mean diameter within the range of 80 - 210 nm. Also they were almost spherical in shape. Effects of the experimental parameters, such as copolymer composition, copolymer concentration, and reaction temperature, on particular size and encapsulation efficiency were investigated.
基金This work was financially supported by the National Project 973 of China and National Science Foundation of China (grantnumber 20004009 and 29934062).
文摘PolyDL-lactide (PDLLA) and the block copolymer, polyDL-lactide-b-poly(ethylene glycol)-b-polyDL-lactide (PELA) were used as the microsphere matrix to encapsulate plasmid DNA. The PDLLA, PELA, pBR322-loaded PDLLA and pBR322-loaded PELA microspheres were prepared by solvent extraction method based on the formation of multiple w1/o/w2 emulsion. The microspheres were characterized by surface morphology, mean particle size, particle size distribution and loading efficiency. The integrity of DNA molecules after being extracted from microspheres was determined by agarose gel electrophoresis. The result suggested that plasmid DNA molecules could retain their integrity after being encapsulated by PELA. The PELA microspheres could prevent plasmid DNA from being digested by DNase. The in vitro degradation and release profiles of plasmid DNA-loaded microspheres were measured in pH = 7.4 buffer solution at 37 °C. The in vitro degradation profiles of the microspheres were evaluated by the deterioration in microspheres surface morphology, the molecular weight reduction of polymer, the mass loss of microspheres, the changes of pH values of degradation medium, and the changes of particle size. The in vitro release profiles of the microspheres were assessed by measurement of the amount of DNA presented in the release medium at determined intervals. The release profiles were correlation with the degradation profiles. The release of plasmid DNA from PELA microspheres showed a similar biphasic trend, that is, an initial burst release was followed by a slow, but sustained release.
文摘Objective To investigate the effect of the implant composite of poly lactide-co-glycolide(PLGA)and bone mesenchymal stem cells (BMSCs) modified by basic fibroblast growth factor (bFGF) on injured spinal cord in rats.Methods Two hundred and
基金Supported by Key Projects in the National Science & Technology Pillar Program During the Eleventh Five-Year Plan Period 2009,China(No.ZX9103-122)
文摘Biodegradable polymer poly(lactic-co-glycolic acid)(PLGA) was used to encapsulate the pharmacological activity metabolite of tolterodine by means of O/W emulsion solvent evaporation method via homogenization in the emulsification process. The influences of preparation parameters were investigated. The results indicate that increa- sing PLGA concentration from 15% to 40% made the encapsulation efficiency of 5-hydroxymethyl derivative of tol- terodine(5-HMT) increased from 55.39% to 76.32%, and the particle size increased from 34.33 μm to 70,78 lain. In addition, when homogenization speed increased from 850 r/min to 2300 r/min, both particle size and encapsulation efficiency of microspheres decreased. An increase in the volume of aqueous phase led to higher encapsulation efficiency and bigger particle size. Increasing temperature made encapsulation efficiency and particle size change significantly. While reaction temperature increased from 20 ℃ to 50 ℃, the encapsulation efficiency decreased from 70.44% to 24.07%, and particle size increased from 38.66 μm to 69.38 μm. High reaction temperature(over 40 ℃) may lead to porous surface of microspheres. Porous surface, encapsulation efficiency and particle size influenced on the in vitro release of 5-HMT together.
基金the National Natural Science Foundation of China, No. 30471759
文摘The purpose of this study was to evaluate the effect of poly(lactide-co-glycolic acid) delayed-release microspheres,which were prepared using glial cell line-derived neurotrophic factor(GDNF),on the delayed-release,controllability,and protection of GDNF activity.The present study is the first to combine chondroitinase ABC,GDNF,and Nogo A antibody delayed-release microspheres for the treatment of spinal cord injury.Results show that the combined therapy of chondroitinase ABC,GDNF,and Nogo A antibody microspheres can increase the immunoreaction of neurofilament 200 in the injured spinal cord,and this therapeutic effect was better than chondroitinase ABC,GDNF,or Nogo A antibody microspheres administered singularly.
文摘When a protein is encapsulated into poly( DL -lactide-co-glycolide)(PLGA) microspheres by means of the double-emulsion method,the harsh microspheres formation process including ultrasonification,exposure to an organic solvent and a polymer may cause the denaturation of the protein. In this study,we investigated the enzymatic activity change and the effect of the excipients on the stability of recombinant human Cu,Zn-superoxide dismutase(rhCu,Zn-SOD) during the emulsification. The specific activity recovery was found to be concentration dependent and the excipients involved such as PEG 600 and Tween 20,and trehalose were shown to increase the stability of rhCu,Zn-SOD. The protein structural integrity within the microspheres was analyzed by FTIR. The structure of rhCu,Zn-SOD within PLGA microspheres containing trehalose was found to be similar to that of the native solid state,whereas the protein encapsulated during the preparation in the absence of any excipient changed due to the possible hydrophobic interaction with the polymer. The results suggest that a rational stability strategy for protein to be encapsulated into microspheres should aim at different processes.
基金National Natural Science Foundations of China(Nos.31271028,31570984)Innovation Program of Shanghai Municipal Education Commission,China(No.13ZZ051)+2 种基金International Cooperation Fund of the Science and Technology Commission of Shanghai Municipality,China(No.15540723400)Open Foundation of State Key Laboratory for Modification of Chemical Fibers and Polymer Materials,China(No.LK1416)“111 Project” Biomedical Textile Materials Science and Technology,China(No.B07024)
文摘The combination of micro-carriers and polymer scaffolds as promising bone grafts have attracted considerable interest in recent decades.The poly(L-lactic acid)/poly(lactic-co-glycolic acid)/polycaprolactone(PLLA/PLGA/PCL)composite scaffold with porous structure was fabricated by thermally induced phase separation(TIPS).Dexamethasone(DEX)was incorporated into PLGA microspheres and then loaded on the PLLA/PLGA/PCL scaffoldtopreparethedesiredcompositescaffold.The physicochemical properties of the prepared composite scaffold were characterized.The morphology of rat bone marrow mesenchymal stem cells(BMSCs)grown on scaffolds was observed using scanning electron microscope(SEM)and fluorescence microscope.The resultsshowedthatthePLLA/PLGA/PCLscaffoldhad interconnected macropores and biomimetic nanofibrous structure.In addition,DEX can be released from scaffold in a sustained manner.More importantly,DEX loaded composite scaffold can effectively support the proliferation of BMSCs as indicated by fluorescence observation and cell proliferation assay.The results suggested that the prepared PLLA/PLGA/PCL composite scaffold incorporating drug-loaded PLGA microspheres could hold great potential for bone tissue engineering applications.