E-SPART Analysis of Poly (D, L-lactide-co-glycolide) Microspheres Formulated for Dry Powder Aerosols

Electrical-single particle aerodynamic relaxation time (E-SPART) analysis was studied as a tool in formulation screening of diy powders for use in aerosol delivery to the lung. The respirable fraction (RF) of drugs delivered by dry powder inhalers (DPIs) can be improved more effectively by using hydrophobic microspheres as carriers. Poly (D,L-lacttde-co-grycolide) microspheres (PLGA) prepared in die respirable size range (3-7 mm) were treated with poryamino acids and isopropanol in order to obtain particles of surface charge suitable for use in DPIs.

The powder formulations were evaluated for their degree of aggregation by cascade impaction following delivery by the Pfeifler® DPI. The IPA treated PLGA microspheres had a significantly higher RF (12.9%) as compared to the PL and PGA treated microspheres (3.3 and 2.4%, respectively), and untreated microspheres (3.8%). Results of electrostatic charge determined by E-SPART analysis suggested that die higher RF for the IPA formulation may be due to hs highly unipolar nature (+ 56.3 mC/g).     

E-SPART Analysis of Poly (D,L-lactide-co-glycolide) Microspheres Formulated for Dry Powder Aerosols

ABSTRACT

Electrical-single particle aerodynamic relaxation time (E-SPART) analysis was studied as a tool in formulation screening of diy powders for use in aerosol delivery to the lung. The respirable fraction (RF) of drugs delivered by dry powder inhalers (DPIs) can be improved more effectively by using hydrophobic microspheres as carriers. Poly (D,L-lacttde-co-grycolide) microspheres (PLGA) prepared in die respirable size range (3-7 mm) were treated with poryamino acids and isopropanol in order to obtain particles of surface charge suitable for use in DPIs.

The powder formulations were evaluated for their degree of aggregation by cascade impaction following delivery by the Pfeifler® DPI. The IPA treated PLGA microspheres had a significantly higher RF (12.9%) as compared to the PL and PGA treated microspheres (3.3 and 2.4%, respectively), and untreated microspheres (3.8%). Results of electrostatic charge determined by E-SPART analysis suggested that die higher RF for the IPA formulation may be due to hs highly unipolar nature (+ 56.3 mC/g).     

Preparation of polymeric micelles consisting of poly(propylene glycol) and poly(caprolactone)

The ring-opening polymerization of epsilon-caprolactone (CL) was carried out with polypropylene glycol (PPG) as an initiator in the presence of the monomer activator HCl. Et2O to synthesize poly(epsilon-caprolactone)-poly(propyleneglycol)-poly(epsilon-caprolactone) (PCL-PPG-PCL) triblock copolymers with change of length PPG and PCL. The micelle formation of PCL-PPG-PCL triblock copolymers in an aqueous phase was confirmed by NMR, dynamic light scattering and fluorescence techniques. The critical micelle concentration (CMC) of the PCL-PPG-PCL triblock copolymers, determined from fluorescence measurements, was in range of 1.4 x 10(-3)-4.6 x 10(-3) mg/ml with dependence on block lengths of PPG and PCL. The partition equilibrium constant, K(v), which is an indicator of the hydrophobicity of the micelles of the PCL-PPG-PCL triblock copolymers in aqueous media, was also changed with dependence on length PPG and PCL. We confirmed that the PCL-PPG-PCL triblock copolymers formed micelles and hence may be potential hydrophobic drug carriers.     

Preparation and characterisation of poly(lactide-co-glycolide) (PLGA) and PLGA/Bioglass® composite tubular foam scaffolds for tissue engineering applications

Polylactide-co-glycolide (PLGA) and PLGA/Bioglass® foams of tubular shape have been prepared with a 1 wt.% 45S5 Bioglass® content. Porous membranes with varying thickness and porosity were fabricated via a thermally induced phase separation process, from which tubes of controlled diameter and wall thickness in the range 1.5–3 mm were produced. Scanning electron microscopy (SEM) revealed that the structure of the tubular foams consisted of radially oriented and highly interconnected pores with two distinct pore sizes, i.e. macropores ∼100-μm average diameter and interconnected micropores of 10–50-μm diameter. Foams with Bioglass® inclusions showed similarly well-defined tubular and interconnected pore morphology. Cell culture studies using mouse fibroblasts (L929) were conducted to assess the biocompatibility of the scaffolds in vitro. L929 fibroblasts cultured in medium that was pre-conditioned by incubating with PLGA tubes containing Bioglass® had a significant reduction in cell proliferation compared with fibroblasts grown in unconditioned medium (p<0.0001).The PLGA and PLGA/Bioglass® tubular foams developed here are candidate materials for soft-tissue engineering scaffolds, holding promise for the regeneration of tissues requiring a tubular shape scaffold, such as intestine, trachea and blood vessels.     

In vitro anti-bacterial and cytotoxic properties of silver-containing poly(L-lactide-co-glycolide) nanofibrous scaffolds

Electrospinning has recently emerged as a leading technique for the formation of nanofibrous structures made of organic and inorganic components. In this study, nanofibrous scaffolds were prepared by electrospining a bend solution of poly(L-lactide-co-glycolide) (PLGA) and silver nanoparticles in 1,1,1,3,3,3,-hexafluoro-2-propanol (HFIP). The resulting fibers ranged from 420 to 590 nm in diameter. To evaluate the possibility of using silver-containing PLGA as a tissue engineering scaffold, experiments on cell viability and antibacterial activity were carried out. As a result, PLGA nanofibrous scaffolds having silver nanoparticles of more than 0.5 wt% showed antibacterial effect against Staphylococcus aureus and Klebsiella pneumonia. Furthermore, silver-containing PLGA nanofibrous scaffolds showed viability, indicating their possible application in the field of tissue engineering.     

Aldehyde-functionalized, water-soluble poly(para-phenylene): synthesis and streptavidin assay using FRET

We have attempted to synthesize water-soluble poly(para-phenylene) derivative, poly{[2,5-bis(3-sulfonatobutoxy)-1,4-phenylene sodium salt]-alt-(1,4-phenylene)} (PPP-SO3). Aldehyde groups, versatile functional intermediate groups for immobilization of biomolecules, were introduced at both ends of PPP-SO3 chain to produce PPP-SO3-CHO. PPP-SO3-CHO showed good solubility in aqueous solution and blue emission color, which was expected as an energy donor in FRET mechanism. Biotin was attached to the polymer end groups via imine linkage to use as a ligand for streptavidin immobilization. The biotin coupled with polymer chain enables the polymer to bind with FITC-streptavidin leading to energy transfer from the blue-emitting polymer to green-emitting FITC via FRET.     

Thermosensitive Y-shaped micelles of poly(oleic acid-Y-N-isopropylacrylamide) for drug delivery

A novel thermosensitive amphiphilic copolymer comprised of two hydrophobic poly(oleic acid) (POA) segments and one hydrophilic poly(N-isopropylacrylamide) (PNIPAAm) segment was designed and synthesized. The structure of the copolymer was confirmed as Y-shaped by FTIR, 1H NMR, and SEC-MALLS analysis. A cytotoxicity study shows that the P(OA-Y-NIPAAm) copolymer exhibits good biocompatibility. The copolymer may self-assemble into micelles in water, with the hydrophobic POA segments at the cores of micelles and the hydrophilic PNIPAAm segments as the outer shells. The resulting micelles demonstrate temperature sensitivity with a lower critical solution temperature (LCST) of 31.5 degrees C and a critical micelle concentration (CMC) of 12.6 mg L(-1). Transmission electron microscopy (TEM) shows that the micelles exhibit a nanospheric morphology within a narrow size range of approximately 10-30 nm. A study of controlled release reveals that the self-assembled micelles have great potential as drug carriers.     

Characterization of poly(L-lysine)-graft-poly(ethylene glycol) assembled monolayers on niobium pentoxide substrates using time-of-flight secondary ion mass spectrometry and multivariate analysis

Control of protein adsorption onto solid surfaces is a critical area of biomaterials and biosensors research. Application of high performance surface analysis techniques to these problems can improve the rational design and understanding of coatings that control protein adsorption. We have used static time-of-flight secondary ion mass spectrometry (TOF-SIMS) to investigate several poly(L-lysine)-graft-poly(ethylene glycol) (PLL-g-PEG) adlayers adsorbed electrostatically onto negatively charged niobium pentoxide (Nb(2)O(5)) substrates. By varying the PEG graft ratio (i.e., the number of lysine monomers per grafted PEG chain) and the molecular weights of the PLL and PEG polymers, the amount of protein adsorption can be tailored between 1 and 300 ng/cm(2). Detailed multivariate analysis using principal component analysis (PCA) of the positive and negative ion TOF-SIMS spectra showed changes in the outermost surface of the polymer films that were related to the density and molecular weight of the PEG chains on the surface. However, no significant differences were noted due to PLL molecular weight, despite observed differences in the serum adsorption characteristics for adlayers of PLL-g-PEG polymers with different PLL molecular weights. From the PCA results, multivariate peak intensity ratios were developed that correlated with the thickness of the adlayer and the enrichment of the PEG chains and the methoxy terminus of the PEG chains at the outermost surface of the adlayer. Furthermore, partial least squares regression was used to correlate the TOF-SIMS spectra with the amount of protein adsorption, resulting in a predictive model for determining the amount of protein adsorption on the basis of the TOF-SIMS spectra. The accuracy of the prediction of the amount of serum adsorption depended on the molecular weight of the PLL and PEG polymers and the PEG graft ratio. The combination of multivariate analysis and static TOF-SIMS provides detailed information on the surface chemistry and insight into the mechanism for protein resistance of the coatings.     

Design,synthesis and physical properties of poly(styrene-butadiene-styrene)/poly(thiourea-azo-sulfone) blends

A new aromatic azo-polymer, poly(thiourea-azo-sulfone), has been synthesized using 1-(4-thiocarbamoylaminophenylsulfonylphenyl)thiourea and diazonium salt solution. Conducting and thermally stable rubbery blends of poly(styrene-block-butadiene-block-styrene) (SBS) triblock copolymer and poly(thiourea-azo-sulfone) (PTAS) were produced by solution blending technique. PTAS possessed fine solubility in polar solvents and high molar mass 63 × 10₃ g moL^?1. Microscopic analysis on SBS/PTAS blends revealed good adhesion between the two polymers without macro phase separation. Electrical conductivity measurement recommended that blending of SBS with 60% PTAS was sufficiently conducting 1.43 S cm^?1. A relationship between PTAS loading and thermal stability of blends was observed. With the increasing PTAS content, 10% gravimetric loss was increased from 481 to 497 °C, while glass transition improved from 123 to 136 °C (better than neat SBS but lower than PTAS). The blends also established higher tensile strength (52.40–59.96 MPa) relative to SBS. Fine balance of properties renders new SBS/PTAS, potential engineering plastics for a number of aerospace relevance.     

高分子量聚乳酸用于SLS快速成型的研究

通过选区激光烧结技术(selective laser sintering,SLS),对高分子量聚(D,L-乳酸)(PDLLA)快速成型加工,研究该技术制造PDLLA组织工程支架的可行性。重均分子量80000,最大粒径120μm的PDLLA粉末,采用SLS技术快速成型,优化得到最佳控制参数,即预热温度为40℃、激光功率为12W、扫描速度1200mm/s。按照该参数加工测试件及人耳状支架,通过GPC-十八角激光光散射联用技术分析材料分子量的变化,力学测试仪分析成型材料的力学性能,扫描电镜分析支架材料的微观结构。结果显示高分子量的PDLLA可用于SLS加工成型,加工过程中高温会引起分子量部分降低,这种变化主要是激光接触面分子量降低所致,烧结作用不会改变材料的主要化学基团,力学测试显示烧结成型的材料能保留加工前聚合物20%的压缩模量,扫描电镜观察成型材料具有多孔结构,显示PDLLA用于SLS加工组织工程支架的潜能。     

Synthesis and characterization of silver nanoparticle composite with poly(p-Br-phenylsilane)

The one-pot synthesis and characterization of silver nanoparticle-poly(p-Br-phenylsilane) composites have been carried out. The conversion of silver(+1) salt to stable silver(0) nanoparticles is promoted by poly(p-Br-phenylsilane), Br-PPS possessing both possible reactive Si-H bonds in the polymer backbone and C-Br bonds in the substituents. The composites were characterized using XRD, TEM, FE-SEM, and solid-state UV-vis analytical techniques. TEM and FE-SEM data show the formation of the composites where large number of silver nanoparticles (less than 30 nm of size) are well dispersed throughout the Br-PPS matrix. XRD patterns are consistent with that for fcc-typed silver. The elemental analysis for Br atom and the polymer solubility confirm that the cleavage of C-Br bond and the Si-Br dative bonding were not occurred appreciably at ambient temperature. Nonetheless, TGA data suggest that some sort of cross-linking was occurred at high temperature. The size and processability of such nanoparticles depend on the ratio of metal to Br-PPS. In the absence of Br-PPS, most of the silver particles undergo macroscopic aggregation, which indicates that the polysilane is necessary for stabilizing the silver nanoparticles.     

Physical stability and lyophilization of poly(epsilon-caprolactone)-b-poly(ethyleneglycol)-b-poly(epsilon-caprolactone) micelles

The stability and lyophilization of core-shell PCL-PEG-PCL micelles were investigated by fluorescence spectra, DLS, DSC, WAXD, and FT-IR. The prepared micelles were not stable when they were stored in aqueous dispersion under different condition. Their size increased in the first 20 days and decreased gradually when the storage period was extended. Lyophilization experiment showed that the cryoprotective agent (glucose) was an essential additive to protect the micelles from aggregating during the lyophilization process. After lyophilizing and re-dispersion, the PCL-PEG-PCL micelles became larger in size compared to as-prepared ones. DSC, WAXD, and IR measurements indicated the hydrogen bonding was formed between the hydroxyl group in glucose and the carbonyl group in PCL-PEG-PCL micelles. The effect of added glucose on protection of micelles from aggregation can be explained by the formation of hydrogen bonding with PCL-PEG-PCL micelles and the formation of solid glucose matrix.     

High-performance silica nanoparticle reinforced poly (vinyl alcohol) as templates for bioactive nanocomposites

Silica nanoparticle reinforced poly (vinyl alcohol) cast sheets 40 μm thick were tested for mechanical and biological properties. The films were characterized using X-ray diffraction, scanning electron microscopy, and infrared spectroscopy. The crystallinity decreased with increased silica content. Changes in the morphology and structure upon the addition of silica suggest the formation of cross-linking. The modulus increased from 300 MPa for PVA to 7.2 GPa for 120 wt.% silica nanoparticle in the blend and the tensile strength increased from 3.5 MPa to 35 MPa. The modulus estimated using dynamic tests, tensile tests, and nanoindentation was comparable and was predicted well using the Halpin-Tsai's equation. The nanocomposites were an order of magnitude tougher than the pure polymer. Silica based nanocomposite was also found to be an excellent template for the deposition of calcium hydroxyapatite when immersed in simulated body fluid. The modulus and tensile strength of apatite coated silica nanoparticle (120 wt.%)–PVA composite increased to 11 GPa and 65 MPa respectively, close to that of cortical bone. The results represent one of the largest increases in mechanical properties of nanocomposite mimicking the properties of human bone. The addition of silica can also aid in osseointegration.     

NMP-DMAC溶剂体系中制备PPTA的研究

以对苯二胺和对苯二甲酰氯为单体,三正丁胺为酸性气体吸收剂,在N-甲基吡咯烷酮和N,N-二甲基乙酰胺的氯化钙的混合溶液体系中,采用低温溶液缩聚法制备了聚对苯二甲酰对苯二胺聚合物。研究了TPC过量值、单体PPD摩尔浓度、溶剂配比、CaCl2用量、TBA用量等因素对聚合物性能的影响。结果表明:当TPC过量值为8‰～9‰、PPD摩尔浓度为0.4 mol/L、溶剂配比为3∶1、CaCl2用量为6%、TBA投加量为PPD摩尔数的2倍时,可以获得性能较佳的PPTA聚合物。与现有的专利技术相比,该合成工艺的混合溶剂体系及酸吸收剂具有新颖性。     

The influences of poly(lactic-co-glycolic acid) (PLGA) coating on the biodegradability, bioactivity, and biocompatibility of calcium silicate bioceramics

Calcium silicate (CaSiO₃) bioceramics and polyesters have complementary qualities as potential bone substituted materials. In this study, sintered CaSiO₃ bioceramics were prepared and coated with poly(lactic-co-glycolic acid) (PLGA), and the influences of the PLGA coating on the degradation, hydrophilicity, bioactivity, and biocompatibility of CaSiO₃ ceramics were investigated. The results showed that the degradation rate was reduced, while hydrophilicity was decreased with the increase of the polymer coating. In addition, the polymer coating resulted in a decrease of the alkaline pH value during the degradation of the ceramics, which indicated an increase of the cell biocompatibility, confirmed by the attachment and proliferation of rMSCs on the surface of the polymer-coated ceramics. Furthermore, the apatite-forming ability of the PLGA-coated CaSiO₃ bioceramics was maintained. This study suggested that the coating with PLGA might be a useful method to improve the integrative properties of CaSiO₃ bioceramics for applications in bone regeneration and bone tissue engineering.     

纳米CdS/聚(苯胺-邻氨基苯甲酸)复合薄膜的荧光性能研究

以聚(苯胺-邻氨基苯甲酸)(PAOAA)为基体,采用原位生成法制备的纳米CdS/PAOAA复合薄膜中,纳米CdS粒子大小均匀,粒径分布窄.对其荧光分析表明,纳米CdS/PAOAA复合薄膜的发光由CdS纳米粒子和PAOAA共同作用产生,在430nm和520nm附近出现了两大发光峰;硫化时间为5h的薄膜表现出的CdS的荧光特征峰与硫化3h的相比,有所增强,而PAOAA的荧光特征峰减弱.     

聚乳酸-羟基乙酸/改性纳米羟基磷灰石复合多孔支架材料的研制

聚乳酸-羟基乙酸(PLGA)/改性纳米羟基磷灰石(MHA)复合多孔组织工程支架材料的制备主要包含以下步骤:首先通过室温化学共沉淀法制备纳米羟基磷灰石,然后通过L-丙交酯在二甲苯溶液中聚合接枝纳米羟基磷灰石得到改性的纳米羟基磷灰石;最后通过改进的热致相分离两步初化法制备PLGA/MHA复合多孔支架.X射线衍射仪(XRD)显示纳米羟基磷灰石合成成功,透射电子显微镜(TEM)结果显示其为半径为30～50nm的球形,红外光谱显示聚乳酸成功的接枝到纳米羟基磷灰石表面;扫描电子显微镜(SEM)结果表明改进的热致相分离两步初化法制备的PLGA/MHA复合多孔支架的孔径在100～450μm.