Preparation of biodegradable magnetic microspheres with poly(lactic acid)-coated magnetite

Poly(lactic acid) (PLA)-coated magnetic nanoparticles were made using uncapped PLA with free carboxylate groups. The physical properties of these particles were compared to those of oleate-coated or oleate/sulphonate bilayer (W40) coated magnetic particles. Magnetic microspheres (MMS) with the matrix material poly(lactide-co-glycolide) (PLGA) or PLA were then formed by the emulsion solvent extraction method with encapsulation efficiencies of 40%, 83% and 96% for oleate, PLA and oleate/sulfonate-coated magnetic particles, respectively. MMS made from PLA-coated magnetite were hemocompatible and produced no hemolysis, whereas the other MMS were hemolytic above 0.3 mg/mL of blood.     

异烟肼乳酸-乙醇酸共聚物磁性微球的制备和体外释放

采用化学共沉法制备磁性Fe3O4纳米粒,再采用W/O/W复乳-溶剂挥干法制备异烟肼乳酸-乙醇酸共聚物[Poly(lactide-co-glycolide),PLGA]磁性微球(INH-PLGA-MMS);电镜考察INH-PLGA-MMS形态、激光粒径分析仪考察粒径分布、磁场计测定磁感应强度、高效液相色谱法(HPLC)测定包封率、载药量及其释放度。结果表明,W/O/W复乳-溶剂挥干法制得的INH-PLGA-MMS外观圆整、表面光滑,平均粒径为3.02μm,磁感应强度为11.403emu/g,平均包封率为62.52%,平均载药量为9.21%,体外释放表明该制剂具有明显的缓释功能,外加振荡磁场可以增加磁性微球中药物的释放。     

Fabrication of Poly(D,L-lactide-co-glycolide) Microspheres and Degradation Characteristics in vitro

Poly(D,L-lactide-co-glycolide) (PLGA, 75/25) microspheres were prepared by the emulsion solvent extraction/evaporation technique and their degradation behaviors in vitro at 37°C were investigated. PLGA microspheres with a smooth and nonporous surface were obtained, with a mean particle size of 114.15 μm. It was observed that mass loss and water uptake of PLGA increased with increasing degradation time; however, weight average molecular weight and the pH value of the phosphate buffered saline (PBS) solution decreased. The observed relative rates of mass loss vs. molecular weight decreases were consistent with the explanation that PLGA underwent bulk degradation rather than surface degradation. During the degradation time, the surface of the PLGA microspheres became coarse and there were many micropores that developed upon immersion in the PBS. The microspheres lost their spherical form with increasing degradation time.     

Surface morphology and in vitro release performance of double-walled PLLA/PLGA microspheres entrapping a highly water-soluble drug

Double-walled microspheres trapping gentamicin sulphate were prepared from poly(l-lactic acid) (PLLA) and poly(l-lactic-co-glycolic acid) (PLGA) as a delivery system for highly hydrophilic antibiotics. The surface and cross-section morphology of the microspheres were characterized by SEM and FTIR. The diameters of the microspheres were ranging from about 50 μm to 700 μm. A low initial burst was achieved. The encapsulation efficiency was more than 70% and the cumulative drug release was about 40% for 30 days. The results indicated that the double-walled microspheres were able to achieve higher encapsulation efficiency and lower initial burst for highly water-soluble drugs.     

Encapsulating doxorubicin-intercalated lamellar nanohydroxyapatite into PLGA nanofibers for sustained drug release

In this work, doxorubicin (DOX) was intercalated into layered nanohydroxyapatite (LHAp). The drug loaded LHAp (DOX@LHAp) was then mixed with poly(lactic-co-glycolic acid) (PLGA) and electrospun to yield DOX@LHAp/PLGA composite scaffolds. As control, needle-like nanohydroxyapatite (nHAp) was also used to make an DOX@nHAp/PLGA composite scaffold and bare DOX was used to fabricate DOX/PLGA scaffold. The morphology, release behavior of DOX, and capability to inhibit cancer cells were assessed. The addition of DOX-loaded nHAp to PLGA causes a slight decrease in the average fiber diameter of DOX@LHAp/PLGA as compared to PLGA. The in vitro drug release tests reveal a much faster release of DOX from DOX/PLGA than DOX@LHAp/PLGA. Moreover, DOX@LHAp/PLGA displays a more sustainable release over DOX@nHAp/PLGA due to the storage of DOX in the gallery of LHAp, which is further proved by their cancer cell inhibition results. We believe that the DOX@LHAp/PLGA scaffold has potential as an implantable drug delivery system.     

Adsorption behavior of protein onto siloxane microspheres

The siloxane microspheres with core-shell structure (PMMA/PMPS) (MMA, methyl methacrylate; MPS, 3-methacryloxypropyl-trimethoxysilane) have been prepared by dispersion polymerization as described in our previous work. In this paper, the developed poly(MMA-MPS) microspheres, as a carrier, are used to investigate the adsorption behavior of bovine serum albumin (BSA) on them. The Langmuir and Freundlich models have been applied to describe the adsorption behavior. The experimental results indicated that the presence of PMPS evidently increases the adsorption rate and the amount of protein, and it also influences the interaction of BSA molecules. The adsorption of BSA on the poly(MMA-MPS) microspheres seems to be sensitive to pH and ionic strength. The fittings curves from Langmuir and Freundlich models showed that the adsorption was actually more complicated than ideal situation because one or more interactions were involved in the process. For understanding the electronic contribution, the Zeta potential was used to measure the reactive system before and after protein adsorption.     

Identification of psoralen loaded PLGA microspheres in rat skin by light microscopy

Drug delivery systems involving the use of polymers are widely studied and discovery of biocompatible polymers has become the focus of research in this area. Psoralen loaded poly(DL-lactide-co-glycolide) (PLGA) microspheres to be used in PUVA therapy (psoralen and UVA irradiation (ultraviolet A, 320-400 nm) of psoriasis were identified in paraffin sections by histological analysis. The psoralen loaded PLGA microspheres were prepared using the solvent evaporation technique. They were spherical and possessed an external smooth surface as observed by scanning electron microscopy (SEM) analysis. This study describes a modification in the routine preparation of microsphere samples for examination by light microscopy. The changes involved fixative agents and/or stains allowing the identification of microspheres containing a non-fluorescent material. The preservation and identification of microspheres in tissues for histological processing in paraffin was greatly improved by these modifications as proven by our results.     

Characterization and activity of sonochemically-prepared BSA microspheres containing Taxol--an anticancer drug

Proteinaceous microspheres of BSA (Bovine Serum Albumin) containing an anticancer drug, Taxol (paclitaxel) were fabricated using a sonochemical procedure and then assayed for chemical and biological activity. The sonochemical reaction did not compromise the drug, which became encapsulated in the BSA microspheres. The amount of the anticancer drug in the microspheres was determined by HPLC. Anticancer activity of the proteinaceous microspheres encapsulating the Taxol was tested on Mouse Multiple Myeloma cell line MPC-11. The influence of the Taxol microspheres on the cancer cells was different from pristine Taxol. It was found that Taxol in combination with the organic solvent causes the death of cancer cells.     

Control of Size and Morphology of Gelatin Microspheres

Gelatin microspheres with different particle size and surface morphology were obtained through an emulsification-coacervation method in water-in-oil (W/O) emulsions. The effect of preparation parameters on the size and morphology of the gelatin microspheres was investigated, and the influence of post-treatment, including washing solvent and freeze-drying, on the surface morphology was also studied. The results showed that spherical microspheres, without aggregation phenomena and with a very smooth and uniform surface, are formed during the cross-linking process. The particle size of the gelatin microspheres increased with increasing concentration of the gelatin solution, emulsifying time, and W/O phase volume ratio; however, the particle size of the gelatin microspheres decreased with increasing concentration of the emulsifier and stirring rate. During the post-treatment process, the surface of the gelatin microspheres collapsed when dehydrated by acetone; the surface morphologies of microspheres were smoother when dehydrated by acetone/water solution with a volume ratio of 5:1 and acetone in sequence. When the obtained smooth gelatin microspheres were soaked in deionized water for 24 h and then treated by freeze-drying method for 12 h, microspheres with porous structure were obtained.     

聚-α-甲基苯乙烯空心微球制备过程中的缺损研究

基于二次乳化技术产生W1/O/W2双重乳液,采用乳液微封装技术制备聚--甲基苯乙烯(PAMS)空心微球,研究了部分工艺参数对PAMS微球缺损形态和比例的影响。实验结果表明:薄壁微球的低强度导致了微球表面缺损。当微球壁厚一定时,有3个因素影响缺损微球比例:W2相中聚乙烯醇质量分数、CaCl2质量分数和O/W2的相比,当它们分别为1.0%,1.5%,0.01时,薄壁(2 m)微球的缺损比例低于40%,球壳内也无气泡存在。     

聚苯乙烯相对分子量对薄壁聚苯乙烯空心微球质量的影响北大核心CSCD

激光惯性约束聚变(ICF)作为探索受控核聚变的有效途径,有望获得清洁无污染的能源,而薄壁聚苯乙烯(PS)空心微球是ICF物理实验中亟需的一类微球。针对薄壁空心微球因径厚比(直径/壁厚)增大导致其在干燥、使用中易开裂的问题,研究了PS原料对薄壁微球质量的影响,探讨了其影响机制。结果表明:当油相PS质量分数为4%时,随着油相粘度增加,W1/O/W2复合乳粒稳定性逐渐提高;当油相质量分数不低于8%时,复合乳粒稳定性良好。PS原料对微球表面粗糙度影响较小,微球球形度和壁厚均匀性随初始油相粘度的增大而降低,在干燥过程中微球开裂率随原料力学性能提高而减小。在外水相中引入氟苯(FB)液滴,延缓固化速率,可减小油相粘度增加对微球球形度和壁厚均匀性的不利影响。     

Preparation of magnetic polylactic acid microspheres and investigation of its releasing property for loading curcumin

In order to obtain a targeting drug carrier system, magnetic polylactic acid (PLA) microspheres loading curcumin were synthesized by the classical oil-in-water emulsion solvent-evaporation method. In the Fourier transform infrared spectra of microspheres, the present functional groups of PLA were all kept invariably. The morphology and size distribution of magnetic microspheres were observed with scanning electron microscopy and dynamic light scattering, respectively. The results showed that the microspheres were regularly spherical and the surface was smooth with a diameter of 0.55-0.75 μm. Magnetic Fe₃O₄ was loaded in PLA microspheres and the content of magnetic particles was 12 wt% through thermogravimetric analysis. The magnetic property of prepared microspheres was measured by vibrating sample magnetometer. The results showed that the magnetic microspheres exhibited typical superparamagnetic behavior and the saturated magnetization was 14.38 emu/g. Through analysis of differential scanning calorimetry, the curcumin was in an amorphous state in the magnetic microspheres. The drug loading, encapsulation efficiency and releasing properties of curcumin in vitro were also investigated by ultraviolet-visible spectrum analysis. The results showed that the drug loading and encapsulation efficiency were 8.0% and 24.2%, respectively. And curcumin was obviously slowly released because the cumulative release percentage of magnetic microspheres in the phosphate buffer (pH=7.4) solution was only 49.01% in 72 h, and the basic release of curcumin finished in 120 h.     

A Simple,Scalable Process for the Production of Porous Polymer Microspheres by Ink‐Jetting Combined with Thermally Induced Phase Separation

Porous microspheres capable of delivering high payloads of biomolecules with suitable biodegradability and biocompatibility would be valuable in delivery systems to aid tissue regeneration. This study describes a facile, scalable technique to produce biodegradable porous microspheres by combining continuous ink‐jetting through a piezoelectric nozzle with thermally induced phase separation (TIPS). A selection of biomaterials is investigated to suit delivery in tissue engineering, the synthetic polyesters poly(lactic‐co‐glycolic acid) (PLGA), and poly caprolactone (PCL) and a natural polymer, gelatin. The parameters governing the microsphere production are determined experimentally and compared to theoretical predictions derived from the fluid mechanics and heat transfer during the ink‐jetting process. The microspheres produced have open interconnected pores with mean particle diameters of 80–200 μm and no significant skin region. The physical properties, such as the mean particle diameter, pore size, and surface area could be controlled by varying production parameters including the ink‐jetting pressure, nozzle height, and the size and oscillation frequency of the nozzle. The technique is demonstrated to successfully encapsulate a model hydrophobic molecule during microsphere production with uniform distribution. Porous PLGA microspheres are also used to achieve much higher adsorption capacities of a short peptide than non‐porous microspheres of the same material.     

A novel approach to preparing magnetic protein microspheres with core-shell structure

Magnetic protein microspheres with core-shell structure were prepared through a novel approach based on the sonochemical method and the emulsion solvent evaporation method. The microspheres are composed of the oleic acid and undecylenic acid modified Fe₃O₄ cores and coated with globular bovine serum albumin (BSA). Under an optimized condition, up to 57.8 wt% of approximately 10 nm superparamagnetic Fe₃O₄ nanoparticles could be uniformly encapsulated into the BSA microspheres with the diameter of approximately 160 nm and the high saturation magnetization of 38.5 emu/g, besides of the abundant functional groups. The possible formation mechanism of magnetic microspheres was discussed in detail.     

Synthesis of Ca-P nanoparticles and fabrication of Ca-P/PHBV nanocomposite microspheres for bone tissue engineering applications

As the first step in producing totally bioresorbable osteoconductive composite scaffolds for bone tissue engineering using the selective laser sintering technology, bioresorbable nanoparticles of calcium phosphate (Ca-P) similar in composition to β-tricalcium phosphate were synthesized and Ca-P nanoparticle filled poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) microspheres were fabricated. The pH of the chemical reaction for Ca-P particle synthesis was found to have significant effects on the morphology and chemical composition of Ca-P precipitated. Ca-P particles produced at the pH of 10.0-11.0 were amorphous, had a Ca:P molar ratio of about 1.5, were spherical in shape and had sizes in the range of 10-30 nm. The Ca-P particles were used to form Ca-P nanocomposite microspheres through a solid-in-oil-in-water (S/O/W) emulsion solvent evaporation process. Ca-P nanoparticles were mostly encapsulated inside the microspheres and some Ca-P nanoparticles were superficially embedded on the microspheres. The Ca-P/PHBV microspheres had an average diameter of about 48 μm which is suitable for selective laser sintering for constructing osteoconductive composite scaffolds.     

紫外-可见光谱法研究Fc(COOH)2和BSA相互作用

采用紫外-可见光谱法(UV-Vis)研究Fc(COOH)₂ (λ_max=255 nm)与BSA(λ_max=277.5) 的相互作用。实验结果表明：Fc(COOH)₂在10~190 μmol·L-1范围内吸光度与浓度呈良好的线性关系(r=0.998 4),BSA在100~1 900 mg·L-1范围内,吸光度与浓度呈良好的线性关系(r=0.999 2),BSA与Fc(COOH)₂反应后,最大吸收波长移至275 nm。当固定Fc(COOH)₂或BSA的浓度时,Fc(COOH)₂或BSA的吸光度随着BSA或Fc(COOH)₂浓度的增加而增大,说明Fc(COOH)₂与BSA存在分子间的相互作用,主要是由于Fc(COOH)₂和 BSA能形成氢键,分子链增长,吸收的能量增加,导致吸光度增大。同时考察Fc(COOH)₂和 BSA的吸光度随时间的变化,70 μmol·L-1的Fc(COOH)₂与1 900 mg·L-1的BSA反应0.1,24和96 h后,在λ_max=275 nm处的吸光度由1.062分别变为1.045和0.986;当700 mg·L-1的BSA与190 μmol·L-1的Fc(COOH)₂反应0.1,24和96 h后,在λ_max=275 nm处的吸光度由0.813分别变为0.794和0.750。     

Biocompatible polymeric implants for controlled drug delivery produced by MAPLE

Implants consisting of drug cores coated with polymeric films were developed for delivering drugs in a controlled manner. The polymeric films were produced using matrix assisted pulsed laser evaporation (MAPLE) and consist of poly(lactide-co-glycolide) (PLGA), used individually as well as blended with polyethylene glycol (PEG). Indomethacin (INC) was used as model drug. The implants were tested in vitro (i.e. in conditions similar with those encountered inside the body), for predicting their behavior after implantation at the site of action. To this end, they were immersed in physiological media (i.e. phosphate buffered saline PBS pH 7.4 and blood). At various intervals of PBS immersion (and respectively in blood), the polymeric films coating the drug cores were studied in terms of morphology, chemistry, wettability and blood compatibility. PEG:PLGA film exhibited superior properties as compared to PLGA film, the corresponding implant being thus more suitable for internal use in the human body. In addition, the implant containing PEG:PLGA film provided an efficient and sustained release of the drug. The kinetics of the drug release was consistent with a diffusion mediated mechanism (as revealed by fitting the data with Higuchi's model); the drug was gradually released through the pores formed during PBS immersion. In contrast, the implant containing PLGA film showed poor drug delivery rates and mechanical failure. In this case, fitting the data with Hixson-Crowell model indicated a release mechanism dominated by polymer erosion.     

Cross-linked gelatin/nanoparticles composite coating on micro-arc oxidation film for corrosion and drug release

A composite coating which could control drug release and biocorrosion of magnesium alloy stent materials WE42 was prepared. This composite coating was fabricated on the surface of the micro-arc oxidation (MAO) film of the magnesium alloy, WE42, by mixing different degrees of cross-linked gelatin with well-dispersed poly(dl-lactide-co-glycolide) (PLGA) nanoparticles. The PLGA nanoparticles were prepared by emulsion solvent evaporation/extraction technique. Nano ZS laser diffraction particle size analyzer detected that the size of the nanoparticles to be 150-300 nm. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) was used to analyze the morphology of the nanoparticles and the composite coating. Potentiodynamic polarization and electrochemical impedance spectroscopy (EIS) were used to evaluate the corrosion behavior of the composite coating. Drug release was determined by ultraviolet-visible (UV-vis) spectrophotometer. The corrosion resistance of the composite coating was improved by preventing the corrosive ions from diffusing to the MAO films. The drug release rate of paclitaxel (PTX) exhibited a nearly linear sustained-release profile with no significant burst releases.     

Preparation and Characterization of Polyacrylonitrile and Polyacrylonitrile/β-cyclodextrins Microspheres

Polyacrylonitrile (PAN) and PAN/β-cyclodextrin (β-CD) microspheres were prepared via an electrospinning method. The PAN microspheres could be successfully obtained in a suitable range of concentrations of electrospun PAN solutions. When β-CD was added to the PAN solutions, electrospun PAN/β-CD composite spheres were prepared. The morphology of the spheres was characterized by scanning electron microscopy (SEM); it showed that the spheres had uniform diameter and a smooth surface. The composition of the composite microspheres was studied by Fourier transform infrared spectroscopy (FTIR). The results showed that the β-CD was incorporated in the polymer microspheres.     

PLGA/G5-T纳米纤维对重金属离子Hg~(2+)的吸附研究

在制革、冶金、电镀、采矿等行业发展过程中,含有重金属离子的废水进入河道和农田,重金属污染越来越受到人们的重视,治理和回收重金属也成为一个亟待解决的难题。其中重金属离子Hg~(2+)被认为是最毒的重金属。为了有效处理含重金属离子Hg~(2+)的废水,将胸腺嘧啶(Thymine)修饰到第五代聚酰胺-胺树状大分子(G5.NH2)表面,得到G5-T,之后将G5-T与聚乳酸羟基乙酸(PLGA)混合并用静电纺丝方法得到PLGA/G5-T混纺纤维,并用傅里叶变换红外光谱(FTIR)、扫描电镜(SEM)等手段对PLGA/G5-T混纺纤维进行了表征,并以电感耦合等离子体发射光谱仪ICP-OES为检测手段,研究PLGA/G5-T对Hg~(2+)的吸附效果。FTIR结果表明,PLGA/G5-T纤维中3 320cm~(-1)处的氨基吸收峰比PLGA/G5上的弱,在1 660cm~(-1)处的酰胺基吸收峰比PLGA/G5强,说明G5.NH2与胸腺嘧啶~(-1)-乙酸成功反应。SEM结果表明,添加了G5-T混纺而得的PLGA/G5-T平均直径为(751±72)nm,纤维形貌均一,表面光滑无粘连,说明G5-T的加入没有破坏纤维的完整性。ICP-OES研究发现,PLGA/G5-T纤维膜对Hg~(2+)的脱除效率明显高于PLGA/G5纤维膜,胸腺嘧啶显著增强了PLGA/G5-T纤维膜对Hg~(2+)的脱除效率;对多种金属离子的吸附实验结果显示,PLGA/G5-T纤维膜对Cu2+,Cd2+和Co2+有微弱的吸附效果,但其对Hg~(2+)吸附效果显著,PLGA/G5-T纤维膜对水溶液中的Hg~(2+)有选择性吸收功能。研究为开发新型Hg~(2+)吸附剂提供了一种新方法。