快速膜乳化法制备载生长激素释放肽-6的PLGA微球

采用快速膜乳化法制备了聚(乳酸-羟基乙酸)(PLGA)微球,得到制备PLGA微球的优化条件为：过膜压力5 kPa,水相中PVA浓度19 g/L,油/水相体积比1:10,该条件下所制空白微球的平均粒径约为24 mm,粒径分布系数Span<0.7. 在此基础上制备载生长激素释放肽-6(GHRP-6)微球,油相乳化剂浓度2.5 g/L、外水相中NaCl浓度10 g/L条件下所制载GHRP-6微球包埋率最高可达85%,初乳制备方式对药物包埋率及体外释放行为均有较大影响,超声法制备的初乳所得微球内部结构紧密,药物包埋率较高(85%),但释药缓慢;而均质法制备的初乳所得微球内部结构疏松,药物包埋率较低(76.8%),但在体外释放更完全.     

快速膜乳化法制备载紫杉醇聚乳酸类微球

采用快速膜乳化法、均质乳化法和超声法制备了聚乳酸(PLA)空白微球,比较了3种方法所制微球的均一性.采用均质乳化法和超声法制备的PLA微球平均粒径分别为1.022和0.987μm,多分散系数分别为0.133和0.145,而快速膜乳化法制备的PLA微球平均粒径为0.906μm,多分散系数为0.005.在此基础上,采用快速膜乳化法制备了聚乳酸、聚(乳酸-羟基乙酸)共聚物(PLGA)和聚(乳酸-聚乙二醇)二嵌段共聚物(PELA)载紫杉醇微球,平均粒径分别为0.906,0.987和1.015μm,多分散系数均为0.005,载药率分别为3.89%,4.93%和3.18%,包埋率分别为63.2%,71.6%和51.3%,在磷酸盐缓冲液中释放60d后,PLGA微球的药物释放率为83.87%,PLA微球为50.25%,PELA微球为41.27%.     

PVA-SA复合微球的制备及性能研究

用溶液共混法制备聚乙烯醇-海藻酸钠(PVA-SA)复合微球,考察了SA质量分数、PVA质量分数、CaCl2质量分数、m(PVA)/m(SA)和干燥方式对PVA-SA复合微球制备的影响,并测定了微球的含水率、溶胀率、载药量和包封率,通过红外光谱(FTIR)对微球进行了表征,研究了不同m(PVA)/m(SA)的PVA-SA复合微球对药物的缓释作用。结果表明,SA质量分数为6%,PVA质量分数为10%,CaCl2质量分数为5%,m(PVA)/m(SA)为1∶3时,可以制备出各项性能较好的微球,其载药率30.24%,包封率90.11%,并且有良好的缓释效果。     

淀粉微球对阿司匹林载药特性的研究

采用反相悬浮聚合法制备淀粉微球,以阿司匹林作为模型药物,吸附法考察淀粉微球的载药性能。以载药量和包封率作为评价指标,探讨投药量浓度、载药时间及载药温度对其载药量的影响。结果表明,投药量质量浓度为0.4 mg/m L,载药时间为90 min,载药温度35℃时,淀粉微球载药量8.21%。可以作为一种优良的阿司匹林吸附载体。     

BG微球/PVA/PLGA复合敷料的制备与表征

利用火焰喷球法制备了19Na_2O-17CaO-64B_2O_3(wt%)钠钙硼(BG)玻璃微球,并将其浸泡于磷酸盐溶液中原位生成BG@HA(羟基磷灰石)微球,然后与聚乙烯醇(PVA)和聚乳酸-羟基乙酸共聚物(PLGA)复合,制备出有一定药物缓释效果的可降解的亲水性复合敷料。复合敷料的失重曲线显示所得敷料可在160h内均匀降解,降解过程中PBS浸泡液pH值较为平稳。采用X射线衍射仪(XRD),红外光谱仪(FTIR)以及场发射环境扫描电镜(SEM)对所得敷料的物相与形貌进行了表征,所得复合敷料中微球相互交联,表面被PLGA覆盖。VB12载药实验结果表明,BG微球/PVA/PLGA复合敷料在70h内具有一定的药物缓释性能,可以用作水溶性药物载体。     

PVC梳状接枝共聚物载药微球的制备与表征

通过点击化学反应,制备了PVC/单甲氧基聚乙二醇梳状接枝共聚物(PVC-g-MPEG),采用SEM观察了其微观结构,测定了以PVC-g-MPEG为载药微球、四氢呋喃为溶剂时毒死蜱的载药量、包封率,考察了以乙醇为溶剂时载药微球中毒死蜱的缓释性能。结果表明:(1)PVC-g-MPEG经剪切乳化后形成了不规则的粒径约1μm的微球;(2)毒死蜱的载药量为49%,包封率为75%;(3)毒死蜱缓释时间达到5.5 h,累积释放量为95%;(4)PVC-g-MPEG的缺点是既不溶解于有机溶剂,也不可降解。     

大蒜素/海藻酸钠/明胶/壳聚糖复合微球的制备及性能

以大蒜素为模型药物,采用复凝聚法制备了海藻酸钠/明胶/壳聚糖复合微球,考察了不同条件对微球溶胀性、载药性能和缓释性能等指标的影响。结果表明,明胶和海藻酸钠(质量比为1∶3)为2%,大蒜素投入量与混合胶比为1∶2时,制备的载药微球(DSGCM)外形规则,粒径分布在0.8~0.9mm之间,载药量为24.3%,包封率为69.4%,复合微球具有p H敏感性,在p H=7.4介质中微球溶胀率达到450%,药物释放过程符合Higuchi方程,明胶的加入可以延缓DSGCM复合微球的药物释放性能。     

聚乳酸-羟基乙酸共聚物微球载药性能的研究

利用三相微流控技术制备聚乳酸-羟基乙酸共聚物(PLGA)微球,并探索微球对水溶性药物的载药量和包封率的影响。结果表明,三相微流控技术制备的PLGA微球大小均一,平均粒径约为49μm。随着内水相模型药物浓度的增加,在保持微球形貌和尺寸均一的前提下,载药量能增加到10. 91%,而药物的包封率仍然维持在96%以上。在PLGA油相中加入油溶性药物,不影响PLGA微球对水溶性药物的载药量和包封率,说明PLGA微球具有优异的载药性能。     

星点设计-效应面法优化鸦胆子油乳酸-羟基乙酸共聚物微球的制备工艺研究

采用乳化溶剂挥发法制备鸦胆子油PLGA微球,以微球的包封率为评价指标,应用星点设计-效应面法考察乳酸-羟基乙酸共聚物(PLGA)的质量浓度、聚乙烯醇(PVA)的质量浓度、鸦胆子油的药物质量浓度对制备工艺的影响,对结果进行多元线性回归和二项式拟合,效应面法优选最佳工艺条件,得到优化后的处方工艺为PLGA质量浓度为6.01mg/m L,PVA的质量浓度为26.52 mg/m L,鸦胆子油的药物质量浓度为90.28 mg/m L,油酸的实测平均包封率为93.8%,与预测值相比,偏差为6.1%。     

壳聚糖聚乙烯醇复合载药微球的制备

以壳聚糖(CS)为基质,通过聚乙烯醇(PVA)的引入制备壳聚糖聚乙烯醇复合载体可以分别采用室温和高温酸催化反应两种方法制备出释药性能和结构形态不同的两种复合载药微球Ⅰ和Ⅱ。其中壳聚糖/聚乙烯醇复合载药微球Ⅰ的制备工艺是调节壳聚糖和聚乙烯醇质量比6/5,复合微球Ⅰ的平均粒径1～20μm,载药量13%,LVFX体外12h累积释放80%。而壳聚糖/聚乙烯醇复合载药微球Ⅱ的平均粒径1.69μm,载药量17.1%,LVFX体外6hr基本完全释放。     

Fabrication of polymer/drug‐loaded hydroxyapatite particle composite fibers for drug sustained release

The aim of this study is to fabricate polymer/hydroxyapatite (HA) particle composite fibers for drug encapsulation and sustained release. Firstly, drug‐loaded hydroxyapatite particles are synthesized in one step, then by electrospinning of the blends of drug‐loaded hydroxyapatite particles and polymer solution the drug‐loaded polymer/hydroxyapatite particle composite fibers are successfully prepared. Effect of loading ratio of drug‐loaded hydroxyapatite particles in the fibers and pH value of the release medium on the drug release kinetics are both investigated, and the results demonstrate that, as compared with the polymer/drug electrospun fibers, the drug in the polymer/drug‐loaded hydroxyapatite particle composite fibers shows a sustained release manner, and the drug release rate can be regulated by both the loading ratio of drug‐loaded hydroxyapatite particles in the composite fibers and pH value of the buffer solution. The results indicate that the developed drug‐loaded polymer/hydroxyapatite particle composite fibers show great potential in bone regeneration and other related biomedical fields. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 42871.     

Kinetics of drug release from drug carrier of polymer/TiO2 nanotubes composite—pH dependent study

This study was to investigate the kinetics of drug release from polymer/TiO₂ nanotubes composite. Lidocaine and carprofen were selected as model drugs to represent weak base and weak acid drugs, respectively. Mathematical models used to fit the in vitro drug release experimental data indicate that at higher pH, the drug release was first order diffusion controlled. At lower pH, the release of the two drugs exhibits two staged controlled release mechanism. The first phase is due to drug diffusion and the second stage is a result of poly(lactic‐co‐glycolic acid) (PLGA) polymer degradation. The rate of drug release from polymer/TiO₂ nanotubes drug carrier was mainly controlled by three pH dependent factors: the solubility of the drug, the degree of polymer swelling/degradation, and the electrostatic force between polymer and drug. This study suggests that controlled release could be achieved for polymer/TiO₂ nanotubes drug carrier via the modulation of pK_a values of polymers and drug solubility. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41570.     

Crosslinked polymer embedded Cu/Ag for comparative drug adsorption and kinetics evaluation

Two-dimensional crosslinked polymer (2-DCP) was synthesized for evaluation of drug adsorption and kinetics thereof. Further, polymer properties were evaluated and parameters such as contact time and adsorption isotherm were also studied. Herein, contact time demonstrated 83% and 85% of drug loading in an acidic medium for two-dimensional crosslinked polymer embedded copper and silver (2-DCP-Cu/Ag), respectively in 24 h. Initial 4 h is the exponential drug loading period whereas drug loading was increased gradually after 4 h. Salbutamol loading was well-fitted to Langmuir adsorption isotherm, which indicated a monolayer drug adsorption with respect to 2-DCP-Cu/Ag. Pseudo first- and pseudo second-order kinetics was evaluated to perceive the drug adsorption mechanism and equilibrium adsorption capacity. Monolayer drug adsorption with chemisorption mechanism was observed for 2-DCP-Cu/Ag. In addition to this, decomposition temperature of polymer was 440 and 325°C while glass transition temperature of polymer was 280 and 200°C before and after metal modification, respectively. (A = aqueous phase; B = organic phase; C = drug solution; D = drug loaded polymer; E = enlarged drug loaded polymer.)     

Controlled drug release carriers based on PCL/PEO/PCL block copolymers

In order to create a new drug delivery system, the ibuprofen-loaded triblock copolymer PCL/PEO/PCL (PCEC) microspheres with a low PEO content (<2?wt%) were prepared by oil in water (o/w) solvent evaporation technique. The influence of PEO content, molecular weight of a polymer matrix and drug loading on the ibuprofen release profiles were evaluated. The interactions between polymer matrix and ibuprofen were detected by FTIR analysis. The presence of hydrophilic PEO segment in PCL chains caused the decrease in particle size, which further had a great impact on the drug release kinetics, i.e., initially faster release and significantly higher quantity of released drug compared to neat PCL. Ibuprofen release behavior from polymer matrix was governed by a diffusion process. In vitro cytotoxicity tests revealed that empty PCL and PCEC microspheres were not toxic at low concentrations, while ibuprofen-loaded microspheres exhibited cytotoxicity correlated with amounts of incorporated drug.     

Preparation of sodium alginate/poly(vinyl alcohol) blend microspheres for controlled release applications

Sodium alginate (NaAlg)/poly (vinyl alcohol) (PVA) blend microspheres (MS) were prepared by water-in-oil (w/o) emulsion method. These polymer microspheres were crosslinked with glutaraldehyde and loaded with metformin hydrochloride (MHC). The microspheres were characterized by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and X-ray diffraction (XRD) analysis to confirm the molecular dispersion of the drug, thermal stability, morphological properties, and crystallinity of the polymer matrix before and after blending. SEM of the microspheres suggested the formation of microspheres in spherical structure. Drug release data were analyzed using an empirical equation to understand the nature of drug transport through polymeric matrices. The controlled release (CR) characteristics of the polymer matrices was investigated in pH 7.4 media and from the results it was obtained that the drug was released in controlled manner up to 10 h. The physico-chemical properties of the microspheres were studied by calculating drug entrapment efficiency and drug release kinetics. Percent of encapsulation efficiency (% EE) decreased with increase in crosslinking agent (GA) and PVA content in the microspheres. The optimum % EE (80%) was observed in case of MS containing 40% of PVA with 15% MHC. The release profiles indicate that the release of MHC decreases with increasing the PVA/NaAlg (w/w) and drug/polymer ratio. At the end of 10 h, the highest release of MHC was found to be 96% for MS containing PVA/NaAlg (40 : 60) and 15 wt % drug loaded. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Supercritical antisolvent coprecipitation in the pharmaceutical field: Different polymeric carriers for different drug releases

The supercritical antisolvent process (SAS) was employed to obtain polymer/drug coprecipitated powders. Indeed, processes based on the use of supercritical fluids allow us to obtain polymer/active drug coprecipitated microparticles with tunable bioavailability. In this work, two different biocompatible polymers were selected to be used as carriers for obtaining drug microparticles with different releases for different applications: polyvinylpyrrolidone (PVP) was coprecipitated with ketoprofen to obtain a rapid drug release and zein was coprecipitated with ampicillin to obtain a controlled drug release. The experiments were performed both on a bench-scale and a pilot-scale plant. Ketoprofen is one of the most prescribed non-steroidal anti-inflammatory drugs. It is poorly soluble in water and, to overcome this inconvenience, in this work, it was coprecipitated with PVP. In correspondence with the optimized polymer/drug ratio, the dissolution rate of the active principle in the coprecipitated particles was about three times higher than the one of the unprocessed ketoprofen. The second model drug under study in this paper is ampicillin, a semi-synthetic penicillin that is one of the most commonly prescribed broad-spectrum antibiotics. Prolonging the release of the drug would imply a reduction in the number of administrations and, therefore, of the side effects associated with too high dosages. For this purpose, in this work, ampicillin was coprecipitated with zein. Zein/ampicillin microparticles were produced up to a polymer/drug ratio of 5/1 w/w; in this case, the antibiotic coprecipitated with zein reaches 90% of its dissolution in about 14 hours, while the unprocessed antibiotic takes about 3 hours to dissolve.     

离子液体中ATRP合成MCC-g-PMAA及其分子对阿司匹林控释的应用

以离子液体氯化1-烯丙基-3-甲基咪唑（[Amim]Cl）为反应介质,利用原子转移自由基聚合（atom transfer radical polymerization,ATRP）法合成了微晶纤维素接枝有聚甲基丙烯酸（MCC-g-PMAA）的pH敏感性聚合物。用透析法将模型药物阿司匹林包覆在聚合物胶束内,并对载药胶束的体外药物释放机制进行研究。通过红外、核磁、透射电镜、X射线衍射和紫外分光光度计等分析手段对聚合物的结构、胶束形貌、胶束对阿司匹林的载药性能及释药性能进行了表征分析。结果表明：聚合物胶束能够在水溶液中自组装成球状胶束,对阿司匹林具有良好的包载效果,阿司匹林在碱性条件下的累积释放量大于酸性条件,载药胶束表现出了良好的pH敏感性和药物缓释性能。     

Preparation of carbon dioxide/propylene oxide/ε-caprolactone copolymers and their drug release behaviors

Summary Poly (propylene-ram-ε-caprolactone carbonate) (PPCL) and poly (propylene carbonate) (PPC) were synthesized by ring-opening copolymerization from carbon dioxide, propylene oxide (PO) and ε-caprolactone (CL) using a polymer-supported bimetallic complexes (PBM) as catalyst. PPC and PPCL microspheres containing a 5-alpha reductase inhibitor, finasteride were elaborated by a conventional oil-in-water (O/W) emulsion-solvent evaporation method. The effects of polymer used on microspheres morphology, size, drug loading, encapsulation efficiency and drug release behaviors were examined. In vitro drug release of these microcapsules was performed in a pH 7.4 phosphate-buffered solution. A prolonged in vitro drug release profile was observed. The release profiles of finasteride from PPC and PPCL microcapsules were found to occur with a burst release followed by a gradual release phase. Drug release rates were dependent upon the properties of the polymer in the microspheres, the higher hydrolytic activity of polymer provided faster release rate.     

Effect of drug loading and laser surface melting on drug release profile from biodegradable polymer

The biodegradable polymer such as poly(l ‐lactic acid) is promising in drug delivery applications because it allows for drug release in a controlled manner. In a polymer‐based drug delivery system, drug release is controlled by polymer degradation and drug loading concentration. In this study, effect of drug concentration on drug release profile is investigated through polymer crystallinity, chain mobility, and polymer degradation, as characterized by the wide‐angle X‐ray diffraction, differential scanning calorimetry, and gel permeation chromatography, respectively. The addition of drug has been shown to accelerate polymer degradation and drug release rate. With a low drug concentration, the slow polymer degradation kinetics results in an induction period of drug release, during which a limited amount of drug is released. The induction period is undesirable because it delays drug release and effectiveness. Since drug release is controlled by polymer degradation, which is a function of polymer crystallinity, laser surface melting is conducted to reduce polymer surface crystallinity and modify its degradation. The effect of laser crystallinity modification on drug release is investigated. A numerical model is also implemented based on hydrolysis and diffusion mechanisms to investigate the effects of drug loading and laser surface melting on polymer degradation and drug release process. It has been demonstrated that laser treatment shortens the induction period of drug release while keeps the release rate unmodified, as desired in drug delivery applications. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 130: 4147–4156, 2013     

Development of ciprofloxacin hydrochloride loaded poly(ethylene glycol)/chitosan scaffold as wound dressing

A novel ciprofloxacin hydrochloride loaded chitosan/poly(ethylene glycol) (PEG) composite scaffold was developed for wound dressing application. PEG incorporation in chitosan scaffold showed enhanced loading up to 5.4 % and increased cumulative release of the drug up to 35 % as compared to pure chitosan scaffold (20 %). The drug loading and control release of the drug has been explained by the morphological features and drug–polymer/polymer–polymer interactions revealed by SEM, FTIR and DSC. Bacterial growth inhibition evaluation using Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus confirmed the efficacy of released drug from the scaffolds (pure and PEG mixed chitosan). Swelling study, bacterial penetration, moisture vapour transmission rate, haematocompatibility and biodegradation profile supported the suitability of scaffold used as wound dressing materials. In-vivo study on mice finally validated the controlled rate of drug release showing the effectiveness of PEG incorporation into the scaffold for quicker and regulated wound healing.