Performance and enhanced oil recovery efficiency of an acid-resistant polymer microspheres of anti-CO_(2) channeling in low-permeability reservoirs

CO_(2) flooding is a vital development method for enhanced oil recovery in low-permeability reservoirs,However,micro-fractures are developed in low-permeability reservoirs,which are essential oil flow channels but can also cause severe CO_(2) gas channeling problems.Therefore,anti-gas channeling is a necessary measure to improve the effect of CO_(2) flooding.The kind of anti-gas channeling refers to the plugging of fractures in the deep formation to prevent CO_(2) gas channeling,which is different from the wellbore leakage.Polymer microspheres have the characteristics of controllable deep plugging,which can achieve the profile control of low-permeability fractured reservoirs.In acidic environments with supercritical CO_(2),traditional polymer microspheres have poor expandability and plugging properties.Based on previous work,a systematic evaluation of the expansion performance,dispersion rheological properties,stability,deep migration,anti-CO_(2) channeling and enhanced oil recovery ability of a novel acid-resistant polymer microsphere(DCNPM-A)was carried out under CQ oilifield conditions(salinity of85,000 mg/L,80℃,pH=3).The results show that the DCNPM-A microsphere had a better expansion performance than the traditional microsphere,with a swelling rate of 13.5.The microsphere dispersion with a concentration of 0.1%-0.5%had the advantages of low viscosity,high dispersion and good injectability in the low permeability fractured core.In the acidic environment of supercritical CO_(2),DCNPM-A microspheres showed excellent stability and could maintain strength for over 60 d with less loss.In core experiments,DCNPM-A microspheres exhibited delayed swelling characteristics and could effectively plug deep formations.With a plugging rate of 95%,the subsequent enhanced oil recovery of CO_(2) flooding could reach 21.03%.The experimental results can provide a theoretical basis for anti-CO_(2)channeling and enhanced oil recovery in low-permeability fractured reservoirs.

Adipose-derived mesenchymal stem cell-incorporated PLLA porous microspheres for cartilage regeneration

Background:In facial plastic surgery,patients with nasal deformity are often treated by rib cartilage transplantation.In recent years,cartilage tissue engineering has developed as an alternative to complex surgery for patients with minor nasal defects via injection of nasal filler material.In this study,we prepared an injectable nasal filler material containing poly-L-l actic acid(PLLA)porous microspheres(PMs),hyaluronic acid(HA)and adipose-derived mesenchymal stem cells(ADMSCs).Methods:We seeded ADMSCs into as-prepared PLLA PMs using our newly invented centrifugation perfusion technique.Then,HA was mixed with ADMSC-i ncorporated PLLA PMs to form a hydrophilic and injectable cell delivery system(ADMSCincorporated PMH).Results:We evaluated the biocompatibility of PMH in vitro and in vivo.PMH has good injectability and provides a favorable environment for the proliferation and chondrogenic differentiation of ADMSCs.In vivo experiments,we observed that PMH has good biocompatibility and cartilage regeneration ability.Conclusion:In this study,a injectable cell delivery system was successfully constructed.We believe that PMH has potential application in cartilage tissue engineering,especially in nasal cartilage regeneration.

Poly(lactic acid)-aspirin microspheres prepared via the traditional and improved solvent evaporation methods and its application performances

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.

Preparation, Characterization and in Vitro Release of Ciprofloxacin Polylactic Acid Microspheres

Aim Ciprofloxacin polylactic acid microspheres (CFX-PLA-MS) were preparedusing solvent evaporation method from a solid-in-oil-in-water emulsion system. Methods Orthogonalexperiment was used to optimize the method of CFX-PLA-MS preparation. Microspheres werecharacterized in terms of morphology, size, encapsulation efficiency, drug loading and in vitro drugrelease. Results The physical state of CFX-PLA-MS was determined by scanning electron microscopy(SEM) and differential scanning calorimetry (DSC) . Microspheres formed were spherical with smoothsurfaces. Drug was enveloped in microspheres without mixing physically with PLA. The averageparticle size was 280.80 ± 0.15 μm, with over 90% of microspheres falling in the range of 250 -390 μm. The encapsulation efficiency was 65.8% ± 0.58% and the drug loading was 34.1% ± 0.51% .In vitro release study revealed a profile of sustained release of Ciprofloxacin from CFX-PLA-MS. Theaccumulated release percentage and half-life (T_(1/2) of Ciprofloxacin microspheres were 84.0% in53.2 h, and 31.9 h, respectively. Higuchi equation was Q= -0.0043 + 0.003 9 t^(1/2), r = 0.9941.Conclusion Ciprofloxacin microspheres have been successfully prepared and sustained release of CFXfrom microspheres is achieved.

Polylactic-co-glycolic acid microspheres containing three neurotrophic factors promote sciatic nerve repair after injury

A variety of neurotrophic factors have been shown to repair the damaged peripheral nerve. However, in clinical practice, nerve growth factor, neurotrophin-3 and brain-derived neuro- trophic factor are all peptides or proteins that may be rapidly deactivated at the focal injury site; their local effective concentration time following a single medication cannot meet the required time for spinal axons to regenerate and cross the glial scar. In this study, we produced polymer sustained-release microspheres based on the polylactic-co-glycolic acid copolymer; the micro- spheres at 300-pm diameter contained nerve growth factor, neurotrophin-3 and brain-derived neurotrophic factor. Six microspheres were longitudinally implanted into the sciatic nerve at the anastomosis site, serving as the experimental group; while the sciatic nerve in the control group was subjected to the end-to-end anastomosis using 10/0 suture thread. At 6 weeks after implanta- tion, the lower limb activity, weight of triceps surae muscle, sciatic nerve conduction velocity and the maximum amplitude were obviously better in the experimental group than in the control group. Compared with the control group, more regenerating nerve fibers were observed and dis- tributed in a dense and ordered manner with thicker myelin sheaths in the experimental group. More angiogenesis was also visible. Experimental findings indicate that polylactic-co-glycolic acid composite microspheres containing nerve growth factor, neurotrophin-3 and brain-derived neurotrophic factor can promote the restoration of sciatic nerve in rats after injury.

Release performance and sustained-release efficacy of emamectin benzoate-loaded polylactic acid microspheres

High-performance liquid chromatography （HPLC） was employed to determine drug release rates based on emamectin benzoate concentrations in the medium. Release kinetics equations were used to fit the drug release behavior. The effects of particle size and release medium pH on the release rate were also investigated. The indoor toxicity of emamectin benzoate-loaded polylactic acid microspheres on the diamondback moth larva （Plutella xylostella） was studied to explore drug sustained-release performance. In acidic and neutral media, the drug release behavior of the microspheres was in accord with the first-order kinetics equation. Increasing the spray dosage of emamectin benzoate-loaded polylactic acid microspheres initially resulted in an equivalent insecticidal efficacy with the conventional emamectin benzoate microemulsion. However, the drug persistence period was four-fold longer than that observed using the conventional formulation. The developed emamectin benzoate-loaded polylactic acid microspheres showed dramatic sustained-release performance. A treatment threshold of greater than 35 mg mL-1 was established for an efficient accumulated release concentration of emamectin benzoate-loaded microspheres.

PREPARATION OF POLY(ETHYLENEGLYCOL-co-ACRYLIC ACID) MICROSPHERES WITH DIVINYLBENZNE AS CROSSLINKER BY DISTILLATION-PRECIPITATION POLYMERIZATION

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.

ERYTHROMYCIN POLYLACTIC ACID MICROSPHERES FOR LUNG TARGETING

AIM: To prepare polylactic acid microspheres of Erythromycin for Lung targeting. METHEDS: The orthogonal test design was used to optimize the technology of preparation. The character of the microspheres, drug release in vitro, stability and tissue distribution were examined. RESULTS: The Erythromycin polylactic acid microspheres was regular in its morphology. Drug was enveloped in microspheres but not physically mixed with PDLLA. The average particle size was 11.65mm with over 94% of the microspheres being in the range of 5~20mm; The drug loading and the incorporation efficiency were 18% and 60% respectively. The microspheres were stable for three month at 4℃ and room temperature. The in vitro release properties could be expressed by the Higuchi抯 equation: y = 28.067 + 3.8515t1/2 (r = 0.9834). Comparing with injection, the drug in microspheres was more concentrated in lung tissue. CONCLUSION: Erythromycin polylactic acid microspheres showed significant sustained release and lung targeting.

Effects of poly lactic-co-glycolic acid-Nogo A antibody delayed-release microspheres on regeneration of injured spinal cord in rats

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.

Preparation of Tolterodine Metabolite Loaded Biodegradable PLGA Microspheres

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.

Preparation of poly(lactide-co-glycolide)microspheres and evaluation of pharmacokinetics and tissue distribution of BDMC-PLGA-MS in rats

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.

Preparation and in vitro Release of Donepezil Hydrochloride Microspheres

[Objectives]To prepare donepezil hydrochloride microspheres and evaluate their quality.[Methods]The donepezil hydrochloride microspheres were prepared by emulsification-solvent evaporation method.The morphology was observed by scanning electron microscopy and the particle size distribution was determined by Laser Diffraction Method.The encapsulation efficiency,drug loading capacity,and in vitro release were determined by HPLC.[Results]The prepared donepezil hydrochloride microspheres were spherical with the average particle diameter of 15.927 μm.The drug loading capacity was 35.62%.The encapsulation efficiency was 90.32%.The drug release in vitro lasted for14 d.The release curve accorded with the first-order kinetic equation.[Conclusions]The prepared donepezil hydrochloride microspheres performed good sustained release effect in vitro,and it was expected to be used for research on Parkinson's disease.

A combination of chondroitinase ABC,glial cell line-derived neurotrophic factor,and Nogo A antibody delayed-release microspheres for the treatment of spinal cord injury

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.

Dexamethasone-Loaded PLGA Microspheres Incorporated PLLA/PLGA/PCL Composite Scaffold for Bone Tissue Engineering

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.

NMR relaxation and diffusion studies to probe the motional dynamics of risperidone within PLGA microsphere

The present study aims to investigate the motional dynamics of risperidone within polylactic co-glycolic acid(PLGA)microsphere by employing solution state'H and 19F nuclear magnetic resonance(NMR)measurements.Risperidone,a second-generation fluorinated antipsychotic drug used for the treatment of schizophrenia is commercially marketed as PLGA microsphere formulation resulting in prolonged release of the drug in solution.Although the current trend in the pharmaceutical market is to develop drug formulation with long-acting release(LAR)products,complete physicochemical characterization of such formulations are scarce.Especially the effects of microsphere encapsulation on the motional properties and diffusion behavior of the drugs are not discussed adequately in any of the earlier reports.We therefore,have employed NMR relaxation and diffusion measurements to decipher the interaction of PLGA cavity water with risperidone.A detailed analysis of NMR relaxation rates confirmed the event of encapsulation and the presence of local motion in the non-fluorinated end of risperidone.Further,the relaxation data indicated a significant alteration in 19F chemical shift anisotropy(CSA)and CSA/dipole-dipole(DD)cross-correlated relaxation mechanism and decreased effect of solvent relaxation pointing out reduced water concentration within the microsphere cavity.'H and 19F diffusion coefficients of risperidone led to the information about hydrodynamic radius of risperidone in free and encapsulated states.Measurement of hydrodynamic radius supported the presence of limited water in PLGA cavity allowing higher translational mobility of risperidone after the encapsulation.

单宁酸缓释微球的制备工艺优化及其体外释放研究

以包封率和载药量为指标,采用单因素实验及正交设计试验对单宁酸微球的制备工艺进行优化,利用扫描电镜(SEM)、傅里叶变换红外光谱(FT-IR)对其结构进行表征分析,并对单宁酸微球在模拟胃液和肠液中的体外释放规律进行了研究。结果表明:制备的微球形状规则,形成了空囊结构。单宁酸微球的最佳制备工艺条件为海藻酸钠与药物(单宁酸)比为1.5∶1、环糊精质量的分数为0.2%、海藻酸酸钠的质量分数2%以及氯化钙的质量分数为0.5%,在此条件下包封率和载药量分别达到95.17%和43.95%。单宁酸微球在人工胃液(pH=1.70)和人工肠液(pH=6.86)中释放24h的累计释放率分别为25.06%、74.26%。微球在模拟胃液中的释放符合Higuchi模型,在肠液中的释放符合一级动力学模型。

聚乳酸多孔微球的表征及性能

采用双乳液溶剂挥发法制备了聚左旋乳酸(PLLA)多孔微球,以精氨酸为氨解试剂对制备的PLLA多孔微球进行表面改性,采用FTIR、SEM、XPS、浸润性测定等方法对改性前后PLLA多孔微球进行表征,考察了微球的细胞毒性和细胞培养性能。实验结果表明,在PLLA多孔微球表面引入羧基和氨基等亲水性基团,使微球的水接触角明显降低;改性后PLLA多孔微球的孔隙率从75.609 8%提高到92.1415%,无细胞毒性,微球表面黏附的细胞数量显著提升,精氨酸改性不但使PLLA多孔微球获得大尺寸、内部贯通的孔隙结构,且在微球表面引入大量亲水功能基团,增加了细胞黏附的结合位点,促进细胞在多孔微球表面的生长、增殖。

再生纤维素微球的制备及其吸附亚甲基蓝和叶酸负载

以微晶纤维素(MCC)的尿素/NaOH溶液为分散相,通过乳液法制备了不同粒径的再生纤维素微球(RCM),考察了RCM对亚甲基蓝吸附行为,并探讨了再生纤维素微球对叶酸(FA)的负载性能。扫描电子显微镜(SEM)结果表明,制备的RCM表面结构粗糙,内部呈一定的中空结构;X射线衍射(XRD)和傅里叶变换红外光谱(FT-IR)结果表明,RCM晶型由Ⅰ型变为Ⅱ型,微球的粒径随转速增大而减小,转速由400 r/min提高至转速1200 r/min时,粒径从286μm降至27μm,减小了约90.56%;随水油体积比(V(MCC)∶V(LP))的减小而减小,V(MCC)∶V(LP)从1∶3降至1∶7时,粒径从311μm降至54μm,减小了约82.64%;随乳化剂质量分数(w(span-80))的增加而减小,当w(span-80)为0.5%时,粒径约为276μm,增大w(span-80)至2.5%时,粒径降至52μm左右,减小了约81.16%。RCM用于吸附亚甲基蓝时,72 h,吸附达到平衡;pH值为10时,吸附能力最强,吸附量为6.11 mg/g;当RCM用量为50 mg时,单位吸附量达到最大值,为4.78 mg/g,符合拟一级吸附动力学模型,吸附过程主要为物理吸附。再生纤维素负载叶酸微球(FCM)的具体负载率可达到98.8%,FCM有效提高了叶酸的储藏稳定性,5 d保留率为74.71%,相对于纯叶酸相比提高了34.7%。

丙磺酸型碗状碳微球制备及在餐厨废油酯交换反应中的性能研究

以碗状碳微球(BHC)为载体,合成了以烷基为磺酸基键合位点的丙磺酸型碗状碳微球(PA-CBHC-Si)。X射线光电子能谱仪、扫描电子显微镜和傅里叶变换红外光谱分析表明,三步改性分别逐步丰富BHC表面羧基(—COOH)、巯基(—SH)、磺酸基(—SO_(3)H)官能团含量,且改性过程保留了载体的原始形貌。PA-CBHC-Si的酸密度高达8.5mmol/g,活性中心—SO_(3)H于300℃开始分解,具有良好的热稳定性。PA-CBHC-Si可作为煎炸废油与甲醇酯交换反应的催化剂,醇油摩尔比为16∶1,剂油比为0.02的催化体系于130℃反应4h,脂肪酸甲酯产率为84.53%。